Genome Research is publishing three papers related to the genome of the gray short-tailed opossum, Monodelphis domestica, a small, nocturnal marsupial found in South America. The papers will appear online, concomitant with the publication of the opossum genome sequence in the journal Nature.
1. A fresh start for immune-related genes
Like all marsupials, opossums are born without a functioning immune system; they develop immunological tissues, organs, and the ability to produce antibodies outside the shelter of the mother's body. The genome sequence of the opossum--the first for any marsupial--provided Dr. Katherine Belov and her colleagues the opportunity to compare immune-related genes in opossums with those in humans.
Belov's team aligned 1528 human immune-related proteins to the opossum genome, and found that the genetic constituents of the human and opossum "immunomes" were quite similar. "Given the similarities, opossums would make an ideal model organism for developmental immunology studies in mammals, including humans," says Belov.
Contact:
Katherine Belov, Ph.D.
University of Sydney, Australia
Reference:
Belov, K., Sanderson, C.E., Deakin, J.E., Wong, E.S.W., Assange, D., McColl, K.A., Gout, A., de Bono, B., Speed, T.P., Trowsdale, J., and Papenfuss, A.T. 2007. Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system. Genome Res.
doi:10.1101/gr.6121807
2. New functions for ancient DNA
Transposable elements (TEs) are mobile, repetitive DNA sequences that can provide insight into evolutionary processes. "The opossum genome has been bombarded by TEs," explains Dr. Andrew Gentles, the first author on a paper that describes the first comprehensive survey of TEs in any marsupial. "TEs cover around 52% of the opossum genome, which is higher than any other amniotic lineage studied to date."
Gentles and his colleagues also discovered ancient TEs that appear to have been recruited for specific biological activities. For example, they identified MER131, a non-protein coding sequence that is highly conserved in the human, chicken, and opossum genomes but absent from zebrafish and frogs. They suggest that MER131 acquired a new function--possibly in regulating gene expression--about 300 million years ago, before the evolutionary divergence of birds and marsupials.
"MER131 is one of many non-coding DNA sequences that are conserved across an amazing variety of species, covering several hundred million years of evolution," says Gentles. "As more genomes are sequenced, we will find more pieces of these molecular jigsaw puzzles that can help us trace the influence of TEs in the development and function of modern genomes."
Contact:
Andrew J. Gentles, Ph.D.
Stanford University, Stanford, CA, USA
Reference:
Gentles, A.J. Wakefield, M.J., Kohany, O., Gu, Wanjun, Batzer, M.A., Pollock, D.D., and Jurka, J. 2007. Evolutionary dynamics of transposable elements in the short-tailed opossum Monodelphis domestica. Genome Res.
doi:10.1101/gr.6070707
3. Colonizing colossal chromosomes
The opossum autosomes (non-sex chromosomes) are unusually large--up to three times longer than the largest human chromosome. When Dr. Leo Goodstadt and his colleagues scrutinized these chromosomes, they discovered that genes situated near the edges of the chromosomes were better at removing mutations that may lead to disease.
"Where a gene lives matters," says Goodstadt. "Genes that lie in the middle of chromosomes are less likely to be shuffled before being passed on to the next generation. So evolution has been pretty good at getting rid of mutations when they're near the ends of chromosomes, but rather poor at doing so in their middles."
In addition, Goodstadt's group identified 2,733 genes that have duplicated in the opossum lineage since its divergence from humans ~170-190 million years ago. These genes contribute to unique physiological and behavioral characteristics in the opossum, including nocturnal foraging, pheromonal communication, immunity, and adaptation to dietary changes.
Contact:
Leo Goodstadt, D.Phil.
University of Oxford, UK
Reference:
Goodstadt, L., Heger, A., Webber, C., and Ponting, C.P. 2007. An analysis of the gene complement of a marsupial, Monodelphis domestica: evolution of lineage-specific genes and giant chromosomes. Genome Res.
doi:10.1101/gr.6093907
ABOUT GENOME RESEARCH:
Genome Research (genome/) is an international, monthly, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.
ABOUT COLD SPRING HARBOR LABORATORY PRESS:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshlpress/.
Contact: Maria Smit
Cold Spring Harbor Laboratory
суббота, 2 июля 2011 г.
пятница, 1 июля 2011 г.
Potential New "Twist" In Breast Cancer Detection
Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called "Twist" may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.
Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.
In experiments designed to identify those special qualities, the Hopkins team focused on the gene "Twist" (or TWIST1) named for its winding shape because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.
"Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer," says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. "The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell."
Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers CD 24 and CD44 even without EMT, announces the presence of this critical sub-group of stem cells.
"The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT," says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. "EMT is not mandatory for identifying a breast cancer stem cell."
Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.
"Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor," Vesuna says. "And here we're talking just 20 cells. There is something about these cells something different compared to the whole bulk of the tumor cell that makes them potent. That's the acid test if you can take a very small number of purified "stem cells" and grow a cancerous tumor, this means you have a pure population."
Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it's not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.
This finding that Twist is integral to the breast cancer stem cell phenotype has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.
This study was supported by the Maryland Stem Cell Research Foundation.
In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.
Source: Johns Hopkins Medicine
Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.
In experiments designed to identify those special qualities, the Hopkins team focused on the gene "Twist" (or TWIST1) named for its winding shape because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.
"Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer," says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. "The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell."
Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers CD 24 and CD44 even without EMT, announces the presence of this critical sub-group of stem cells.
"The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT," says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. "EMT is not mandatory for identifying a breast cancer stem cell."
Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.
"Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor," Vesuna says. "And here we're talking just 20 cells. There is something about these cells something different compared to the whole bulk of the tumor cell that makes them potent. That's the acid test if you can take a very small number of purified "stem cells" and grow a cancerous tumor, this means you have a pure population."
Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it's not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.
This finding that Twist is integral to the breast cancer stem cell phenotype has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.
This study was supported by the Maryland Stem Cell Research Foundation.
In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.
Source: Johns Hopkins Medicine
четверг, 30 июня 2011 г.
News From The Journal Of Biological Chemistry
Nicotine's Effects are Receptor Specific
Following chronic nicotine exposure, nicotine receptors increase in number, an upregulation that contributes to nicotine's addictive properties. While a current belief is that this process is independent of the type of nicotine receptor, researchers have now uncovered this is not the case: the transient and prolonged changes in the nicotine levels of smokers each affect a specific receptor subtype.
The predominant subtype of nicotine receptor in the brain is known as A4B2; these receptors upregulate as nicotine levels gradually rise in the blood. Generally, they start increasing about 2-3 hours following exposure and peak after about 20 hours.
Due to lower prevalance, the upregulation, if any, of minor nicotine receptor subtypes has been difficult, but William Green and colleagues successfully developed cells expressing A6B2 nicotine receptors. They then demonstrated this class also undergoes nicotine upregulation, but at a much faster rate; A6B2 receptors increase within minutes of exposure and peak after only 2 hours.
These receptors also required about 10 times as much nicotine to stimulate as A4B2 receptors, a level that would only be reached during the brief spikes in nicotine levels occurring during smoking. These results offer new insights into the different phases of smoking, highlighting that separate receptors modulate the immediate and long term effects of nicotine.
Corresponding Authors: William Green, Department of Neurobiology, University of Chicago, Illinois
Two-protein Complex Protects Nerve Cells
Since its discovery as a protein that gets specifically released in response to brain injury, ciliary neurotrophic factor (CNTF) has prompted much interest as a potential therapeutic agent. However, numerous experiments have met with limited success, until now; a research team shows that co-administrating CNTF with its receptor promotes the growth and survival of neurons.
While the receptor for CNTF is normally tied to the surface of neurons, this tether is frequently chopped off during trauma, which led Mark Ozog, Christian Naus and colleagues to suspect that CNTF and the free-floating receptor might act in a complex.
They treated mouse neurons with CNTF, its receptor (CNTFR), or both and then exposed the cells to massive amounts of the neurotransmitter glutamate, enough to kill the neurons by over-stimulating them. CNTF or CNTFR alone did not protect the neurons, but the two complexed together could. In addition, the complex could foster increased growth of nerve cells.
Ozog, Naus and colleagues next ran a microarray analysis of the CNTF complex and found that it altered the expression of 47 genes associated with nerve growth and survival, suggesting it protects neurons through multiple direct and indirect mechanisms and thus making it a strong therapeutic candidate.
Corresponding Author: Christian Naus, Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, CA
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
Following chronic nicotine exposure, nicotine receptors increase in number, an upregulation that contributes to nicotine's addictive properties. While a current belief is that this process is independent of the type of nicotine receptor, researchers have now uncovered this is not the case: the transient and prolonged changes in the nicotine levels of smokers each affect a specific receptor subtype.
The predominant subtype of nicotine receptor in the brain is known as A4B2; these receptors upregulate as nicotine levels gradually rise in the blood. Generally, they start increasing about 2-3 hours following exposure and peak after about 20 hours.
Due to lower prevalance, the upregulation, if any, of minor nicotine receptor subtypes has been difficult, but William Green and colleagues successfully developed cells expressing A6B2 nicotine receptors. They then demonstrated this class also undergoes nicotine upregulation, but at a much faster rate; A6B2 receptors increase within minutes of exposure and peak after only 2 hours.
These receptors also required about 10 times as much nicotine to stimulate as A4B2 receptors, a level that would only be reached during the brief spikes in nicotine levels occurring during smoking. These results offer new insights into the different phases of smoking, highlighting that separate receptors modulate the immediate and long term effects of nicotine.
Corresponding Authors: William Green, Department of Neurobiology, University of Chicago, Illinois
Two-protein Complex Protects Nerve Cells
Since its discovery as a protein that gets specifically released in response to brain injury, ciliary neurotrophic factor (CNTF) has prompted much interest as a potential therapeutic agent. However, numerous experiments have met with limited success, until now; a research team shows that co-administrating CNTF with its receptor promotes the growth and survival of neurons.
While the receptor for CNTF is normally tied to the surface of neurons, this tether is frequently chopped off during trauma, which led Mark Ozog, Christian Naus and colleagues to suspect that CNTF and the free-floating receptor might act in a complex.
They treated mouse neurons with CNTF, its receptor (CNTFR), or both and then exposed the cells to massive amounts of the neurotransmitter glutamate, enough to kill the neurons by over-stimulating them. CNTF or CNTFR alone did not protect the neurons, but the two complexed together could. In addition, the complex could foster increased growth of nerve cells.
Ozog, Naus and colleagues next ran a microarray analysis of the CNTF complex and found that it altered the expression of 47 genes associated with nerve growth and survival, suggesting it protects neurons through multiple direct and indirect mechanisms and thus making it a strong therapeutic candidate.
Corresponding Author: Christian Naus, Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, CA
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
среда, 29 июня 2011 г.
Key Developmental Pathway Activates Lung Stem Cells
Researchers from the University of Pennsylvania School of Medicine found that the activation of a molecular pathway important in stem cell and developmental biology leads to an increase in lung stem cells. Harnessing this knowledge could help develop therapies for lung-tissue repair after injury or disease. The investigators published their findings online last week in advance of print publication in Nature Genetics.
"The current findings show that increased activity of the Wnt pathway leads to expansion of a type of lung stem cell called bronchioalveolar stem cells," says senior author Edward Morrisey, Ph.D., Associate Professor of Medicine and Cell and Developmental Biology.
"This information will give us a more extensive basic understanding of Wnt signaling in adult tissue repair in the lung and other tissues and also start to help us determine whether pharmacological activation or inhibition of this pathway can be utilized for treatments," explains Morrisey, who is also the Scientific Director of the Penn Institute for Regenerative Medicine.
Activation of the Wnt signaling pathway leads to expansion, or increase in number, of bronchioalveolar stem cells in the lung. A protein called GATA6 inhibits Wnt signaling by directly regulating the expression of another protein in the Wnt pathway called frizzled 2 (Fzd2).
Wnt signaling is a major pathway in stem cell biology. The finding that GATA6 negatively regulates Wnt signaling and that GATA6 has been shown to play important roles in embryonic stem cell replication and differentiation suggests that these two pathways are linked not only in lung stem cells but in other tissues where they play important roles including the heart, gut, and pancreas.
"We were surprised by the robust activation of Wnt signaling after loss of GATA6 expression in the lung," says Morrisey. "Such a robust activation is rarely observed."
Wnt signaling can be pharmacologically modulated with compounds, including lithium, already approved by the FDA. Use of such compounds, both known and newly identified through ongoing screens, could allow for forced expansion and differentiation of key stem cell populations in the lung and other tissues for adult tissue repair after injury or disease.
Future directions of the Morrisey lab include not only a more extensive basic understanding of Wnt signaling in adult-tissue repair in the lung and other tissues, but also starting to determine whether pharmacological activation or inhibition of this pathway can really be utilized for treatments.
Penn co-authors are Yuzhen Zhang, Ashley M. Goss, Ethan David Cohen, Rachel Kadzik, John J. Lepore, Karthika Muthukumaraswamy. Jifu Yang, and Michael Parmacek. This work was funded by the National Institutes of Health.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Karen Kreeger
University of Pennsylvania School of Medicine
"The current findings show that increased activity of the Wnt pathway leads to expansion of a type of lung stem cell called bronchioalveolar stem cells," says senior author Edward Morrisey, Ph.D., Associate Professor of Medicine and Cell and Developmental Biology.
"This information will give us a more extensive basic understanding of Wnt signaling in adult tissue repair in the lung and other tissues and also start to help us determine whether pharmacological activation or inhibition of this pathway can be utilized for treatments," explains Morrisey, who is also the Scientific Director of the Penn Institute for Regenerative Medicine.
Activation of the Wnt signaling pathway leads to expansion, or increase in number, of bronchioalveolar stem cells in the lung. A protein called GATA6 inhibits Wnt signaling by directly regulating the expression of another protein in the Wnt pathway called frizzled 2 (Fzd2).
Wnt signaling is a major pathway in stem cell biology. The finding that GATA6 negatively regulates Wnt signaling and that GATA6 has been shown to play important roles in embryonic stem cell replication and differentiation suggests that these two pathways are linked not only in lung stem cells but in other tissues where they play important roles including the heart, gut, and pancreas.
"We were surprised by the robust activation of Wnt signaling after loss of GATA6 expression in the lung," says Morrisey. "Such a robust activation is rarely observed."
Wnt signaling can be pharmacologically modulated with compounds, including lithium, already approved by the FDA. Use of such compounds, both known and newly identified through ongoing screens, could allow for forced expansion and differentiation of key stem cell populations in the lung and other tissues for adult tissue repair after injury or disease.
Future directions of the Morrisey lab include not only a more extensive basic understanding of Wnt signaling in adult-tissue repair in the lung and other tissues, but also starting to determine whether pharmacological activation or inhibition of this pathway can really be utilized for treatments.
Penn co-authors are Yuzhen Zhang, Ashley M. Goss, Ethan David Cohen, Rachel Kadzik, John J. Lepore, Karthika Muthukumaraswamy. Jifu Yang, and Michael Parmacek. This work was funded by the National Institutes of Health.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Karen Kreeger
University of Pennsylvania School of Medicine
вторник, 28 июня 2011 г.
Tree Of Life Award Received By Jefferson Doctor
Edith P. Mitchell, M.D., clinical professor, Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University and associate director of Diversity Programs for the Kimmel Cancer Center at Jefferson, was recently honored with a 'Tree of Life' award from The Wellness of You, a local nonprofit health education and resource organization.
The Tree of Life award recognizes health professionals who are committed to making a difference in community health. Recipients of this coveted award have made extraordinary contributions to health management in both the local and global community. Recipients include educators, physicians, authors, community activists, and masters of various disciplines such as martial arts and feng shui.
"I am honored to accept this award from The Wellness of You organization whose purpose is to help individuals in medically underserved areas realize that simple changes in lifestyle can have a dramatic impact on one's health," said Dr. Mitchell. "Their mission matches my own in regards to the importance of community outreach especially to those individuals who may not have the means to seek out more conventional medical advice."
Dr. Mitchell received a bachelor of science in Biochemistry "with distinction" from Tennessee State University and her medical degree from the Medical College of Virginia in Richmond. In 1973, while attending medical school, Dr. Mitchell entered the Air Force and received a commission through the Health Professions Scholarship Program. She entered active duty after completion of her internship and residency in Internal Medicine at Meharry Medical College and a fellowship in Medical Oncology at Georgetown University.
Dr. Mitchell's research in pancreatic cancer and other GI malignancies involves new drug evaluation and chemotherapy, development of new therapeutic regimens, chemoradiation strategies for combined modality therapy, patient selection criteria and supportive care for patients with gastrointestinal cancer. She travels nationally and internationally teaching and lecturing on the treatment of gastrointestinal malignancies.
Dr. Mitchell has authored and co-authored more than 100 articles, book chapters, and abstracts on cancer treatment, prevention, and cancer control. As a distinguished researcher, she has received 21 Cancer Research and Principal Investigator Awards, and serves on the National Cancer Institute Review Panel and the Cancer Investigations Review Committee.
In addition to her medical achievements, Dr. Mitchell is a retired Brigadier General having served as the Air National Guard Assistant to the Command Surgeon for US Transportation command and headquarters Air Mobility Command (AMC) based at the Scott Air Force Base in Illinois. In this capacity she served as the senior medical Air National Guard advisor to the command surgeon and was the medical liaison between the active Air Force and the Air National Guard. Her responsibilities in this role included ensuring maximum wartime readiness and combat support capability of the worldwide patient movement and aero medical evacuation system, the Global Patient Movement Requirements Center and AMC's 52 Air National Guard medical squadrons.
General Mitchell has been awarded over 15 military service medals and ribbons including the Legion of Merit, Meritorious Service Medal, Air Force Achievement and Commendation Medals, National Defense Service Medal, and Humanitarian Service Medal. Dr. Mitchell was selected for inclusion in America's Top Oncologists. Dr. Mitchell is a Fellow of the American College of Physicians and a member of the American Medical Association, the National Medical Association, Aerospace Medical Association, Association of Military Surgeons, and the Medical Society of Eastern Pennsylvania. She is also a member of the Eastern Cooperative Oncology Group, Radiation Therapy Oncology Group, National Surgical Adjuvant Breast and Bowel Project, and the Philadelphia Society of Medicine.
Source: Ed Federico
Thomas Jefferson University
The Tree of Life award recognizes health professionals who are committed to making a difference in community health. Recipients of this coveted award have made extraordinary contributions to health management in both the local and global community. Recipients include educators, physicians, authors, community activists, and masters of various disciplines such as martial arts and feng shui.
"I am honored to accept this award from The Wellness of You organization whose purpose is to help individuals in medically underserved areas realize that simple changes in lifestyle can have a dramatic impact on one's health," said Dr. Mitchell. "Their mission matches my own in regards to the importance of community outreach especially to those individuals who may not have the means to seek out more conventional medical advice."
Dr. Mitchell received a bachelor of science in Biochemistry "with distinction" from Tennessee State University and her medical degree from the Medical College of Virginia in Richmond. In 1973, while attending medical school, Dr. Mitchell entered the Air Force and received a commission through the Health Professions Scholarship Program. She entered active duty after completion of her internship and residency in Internal Medicine at Meharry Medical College and a fellowship in Medical Oncology at Georgetown University.
Dr. Mitchell's research in pancreatic cancer and other GI malignancies involves new drug evaluation and chemotherapy, development of new therapeutic regimens, chemoradiation strategies for combined modality therapy, patient selection criteria and supportive care for patients with gastrointestinal cancer. She travels nationally and internationally teaching and lecturing on the treatment of gastrointestinal malignancies.
Dr. Mitchell has authored and co-authored more than 100 articles, book chapters, and abstracts on cancer treatment, prevention, and cancer control. As a distinguished researcher, she has received 21 Cancer Research and Principal Investigator Awards, and serves on the National Cancer Institute Review Panel and the Cancer Investigations Review Committee.
In addition to her medical achievements, Dr. Mitchell is a retired Brigadier General having served as the Air National Guard Assistant to the Command Surgeon for US Transportation command and headquarters Air Mobility Command (AMC) based at the Scott Air Force Base in Illinois. In this capacity she served as the senior medical Air National Guard advisor to the command surgeon and was the medical liaison between the active Air Force and the Air National Guard. Her responsibilities in this role included ensuring maximum wartime readiness and combat support capability of the worldwide patient movement and aero medical evacuation system, the Global Patient Movement Requirements Center and AMC's 52 Air National Guard medical squadrons.
General Mitchell has been awarded over 15 military service medals and ribbons including the Legion of Merit, Meritorious Service Medal, Air Force Achievement and Commendation Medals, National Defense Service Medal, and Humanitarian Service Medal. Dr. Mitchell was selected for inclusion in America's Top Oncologists. Dr. Mitchell is a Fellow of the American College of Physicians and a member of the American Medical Association, the National Medical Association, Aerospace Medical Association, Association of Military Surgeons, and the Medical Society of Eastern Pennsylvania. She is also a member of the Eastern Cooperative Oncology Group, Radiation Therapy Oncology Group, National Surgical Adjuvant Breast and Bowel Project, and the Philadelphia Society of Medicine.
Source: Ed Federico
Thomas Jefferson University
понедельник, 27 июня 2011 г.
Turning Carbon Nanotubes Into Cellular Probes With Surface Enhanced Raman Spectroscopy
Carbon nanotubes (CNTs) have shown great potential for use as cellular probes. As "nanopipes" they can be used to transport liquids to or from cells and inject solutions or drugs directly into individual cells and individual organelles within the cells. In addition, because of the small diameters of the carbon nanotubes induce little damage to cells upon penetration. By making these probes able to sense within the cells, information about chemical interactions within the cells could be found. Surface-enhanced Raman Spectroscopy (SERS) has this capability.
A journal article just released on the nanotechnology website AZoNano examines making carbon nanotubes SERS active by functionalization with SERS active nanoparticles. This creates the possibility of extremely sensitive study and identification of components of cells. In addition, the nanotubes can be applied to a nanofluidic device where they can serve as an interconnection between a fluid reservoir and the cell, to both deliver and extract fluids. The effects of the fluids on the cells could be studied in situ.
The paper by Alia Sabur from Drexel University has been released as part of the open access journal, AZoJono*. The research found that carbon nanotubes and nanopipes can be used as SERS probes by two different methods that achieved identical results. Combining these SERS active nanotubes with already existing nano-probing techniques could enable the study of cells with single-molecule sensitivity.
Click here to view the article in full.
*AZojono publishes high quality articles and papers on all aspects of nanomaterials and related technologies. All the contributions are reviewed by a world class panel of editors who are experts in a wide spectrum of materials science.
AZojono is based on the patented OARS (Open Access Rewards System) publishing protocol. The OARS protocol represents a unique development in the field of scientific publishing -- the distribution of online scientific journal revenue between the authors, peer reviewers and site operators with no publication charges, just totally free to access high quality, peer reviewed materials science. [See azonano/nanotechnology%20journal.asp and azonano/journal_of_nanotechnology.asp]
Source: Dr. Ian Birkby
AZoNetwork
A journal article just released on the nanotechnology website AZoNano examines making carbon nanotubes SERS active by functionalization with SERS active nanoparticles. This creates the possibility of extremely sensitive study and identification of components of cells. In addition, the nanotubes can be applied to a nanofluidic device where they can serve as an interconnection between a fluid reservoir and the cell, to both deliver and extract fluids. The effects of the fluids on the cells could be studied in situ.
The paper by Alia Sabur from Drexel University has been released as part of the open access journal, AZoJono*. The research found that carbon nanotubes and nanopipes can be used as SERS probes by two different methods that achieved identical results. Combining these SERS active nanotubes with already existing nano-probing techniques could enable the study of cells with single-molecule sensitivity.
Click here to view the article in full.
*AZojono publishes high quality articles and papers on all aspects of nanomaterials and related technologies. All the contributions are reviewed by a world class panel of editors who are experts in a wide spectrum of materials science.
AZojono is based on the patented OARS (Open Access Rewards System) publishing protocol. The OARS protocol represents a unique development in the field of scientific publishing -- the distribution of online scientific journal revenue between the authors, peer reviewers and site operators with no publication charges, just totally free to access high quality, peer reviewed materials science. [See azonano/nanotechnology%20journal.asp and azonano/journal_of_nanotechnology.asp]
Source: Dr. Ian Birkby
AZoNetwork
воскресенье, 26 июня 2011 г.
New Approach For Treatment Of The AIDS Virus?
The AIDS-causing HIV specifically counteracts the mechanisms of human cells that protect these against viral infections - a special viral protein marks protective cellular proteins for their rapid destruction and thus diminishes the cell's supply. A team of researchers in Heidelberg under supervision of virologist Dr. Oliver Keppler demonstrated this mechanism for the first time in cell cultures, thus discovering a target for a novel treatment strategy.
Another important discovery of the Heidelberg virologists - this strategy of the human HIV is not effective in a rat model for AIDS. The protective protein in rats is immune to HIV counteraction. Consequently, HIV cannot propagate itself as easily in the animal model as in humans - one limitation of the current rat model. However, this new knowledge may enable an improvement of the small animal model developed by the Heidelberg researchers. The study was published in the journal Cell Host & Microbe in March 2009.
Newly formed viruses are retained at the cell surface
In addition to the immune system, the body can activate other protective mechanisms to fight or stop virus infections - the infected cells themselves dispose of several proteins that inhibit various steps of virus reproduction. In the presence of the protective protein CD317, newly formed viruses are tethered to the cell surface when they are in the process of leaving the cell and this prevents them from infecting other cells of the body. HIV overcomes this restriction by its protein Vpu by specifically counteracting this protective mechanism, which, interestingly, is effective against many types of viruses.
Dr. Keppler's team of virologists from the Department of Virology at the Hygiene Institute of Heidelberg University Hospital (Medical Director: Professor Dr. Hans-Georg Kräusslich) studied how Vpu disrupts protection by CD317. They determined that in human cells in which Vpu was formed after infection with HIV, the pool of CD317 was reduced to about one quarter of the original amount. "When Vpu is present, CD317 is rapidly degraded by a cellular system. Vpu presumably binds to the CD317 and marks it for rapid destruction," explains Dr. Keppler.
The less CD317 is present in the cell, the more viruses can escape interception. "Disrupting this interaction between Vpu and CD317 to increase the cells' own protective mechanisms could thus be a promising strategy for therapy," says Dr. Keppler.
Rats and mice also have this protective protein; it has the same function and is able to block HIV. However, there is a significant difference - the Heidelberg virologists discovered that in rat cells, Vpu has no effect on CD317. "HIV is adapted to humans and the disruptive mechanism of Vpu does not affect protection against infection in animals," said Dr. Christine Goffinet, first author of the study.
Rat model now to be improved
This detail is important when one wants to imitate and study HIV infection in rats in an animal model - the infection in rats does not follow the same course as in humans, since fewer viruses are released due to the intact protective mechanisms. Based on the new research results, the Heidelberg scientists now hope to improve the current transgenic rat model of HIV infection. The goal is to suppress CD317 in rats through genetic engineering and thus achieve a degree of HIV infection that is more similar to that in humans.
As early as 2007, the researchers in Heidelberg first succeeded in making rats susceptible to HIV infection by specifically modifying their genetic material. They successfully tested drugs against HIV infection in humans in these transgenic rats. Using this small animal model, it is possible to test the efficacy of medications against the AIDS virus HIV rapidly and on a larger scale prior to clinical studies in humans and thus to accelerate the further development of virostatics.
Notes:
References:
Christine Goffinet, Hans-Georg Kräusslich, and Oliver T. Keppler: HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor. Cell Host & Microbe 5, 285-297, March 19, 2009. DOI 10.1016/j.chom.2009.01.009
Heidelberg University Hospital and Medical Faculty:
Internationally recognized patient care, research, and teaching
Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 7,000 employees, training and qualification is an important issue. Every year, around 500,000 patients are treated on an inpatient or outpatient basis in more than 40 clinics and departments with 1,600 beds. Currently, about 3,100 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany.
Source:
PD Dr. med. Oliver T. Keppler
University Hospital Heidelberg
Another important discovery of the Heidelberg virologists - this strategy of the human HIV is not effective in a rat model for AIDS. The protective protein in rats is immune to HIV counteraction. Consequently, HIV cannot propagate itself as easily in the animal model as in humans - one limitation of the current rat model. However, this new knowledge may enable an improvement of the small animal model developed by the Heidelberg researchers. The study was published in the journal Cell Host & Microbe in March 2009.
Newly formed viruses are retained at the cell surface
In addition to the immune system, the body can activate other protective mechanisms to fight or stop virus infections - the infected cells themselves dispose of several proteins that inhibit various steps of virus reproduction. In the presence of the protective protein CD317, newly formed viruses are tethered to the cell surface when they are in the process of leaving the cell and this prevents them from infecting other cells of the body. HIV overcomes this restriction by its protein Vpu by specifically counteracting this protective mechanism, which, interestingly, is effective against many types of viruses.
Dr. Keppler's team of virologists from the Department of Virology at the Hygiene Institute of Heidelberg University Hospital (Medical Director: Professor Dr. Hans-Georg Kräusslich) studied how Vpu disrupts protection by CD317. They determined that in human cells in which Vpu was formed after infection with HIV, the pool of CD317 was reduced to about one quarter of the original amount. "When Vpu is present, CD317 is rapidly degraded by a cellular system. Vpu presumably binds to the CD317 and marks it for rapid destruction," explains Dr. Keppler.
The less CD317 is present in the cell, the more viruses can escape interception. "Disrupting this interaction between Vpu and CD317 to increase the cells' own protective mechanisms could thus be a promising strategy for therapy," says Dr. Keppler.
Rats and mice also have this protective protein; it has the same function and is able to block HIV. However, there is a significant difference - the Heidelberg virologists discovered that in rat cells, Vpu has no effect on CD317. "HIV is adapted to humans and the disruptive mechanism of Vpu does not affect protection against infection in animals," said Dr. Christine Goffinet, first author of the study.
Rat model now to be improved
This detail is important when one wants to imitate and study HIV infection in rats in an animal model - the infection in rats does not follow the same course as in humans, since fewer viruses are released due to the intact protective mechanisms. Based on the new research results, the Heidelberg scientists now hope to improve the current transgenic rat model of HIV infection. The goal is to suppress CD317 in rats through genetic engineering and thus achieve a degree of HIV infection that is more similar to that in humans.
As early as 2007, the researchers in Heidelberg first succeeded in making rats susceptible to HIV infection by specifically modifying their genetic material. They successfully tested drugs against HIV infection in humans in these transgenic rats. Using this small animal model, it is possible to test the efficacy of medications against the AIDS virus HIV rapidly and on a larger scale prior to clinical studies in humans and thus to accelerate the further development of virostatics.
Notes:
References:
Christine Goffinet, Hans-Georg Kräusslich, and Oliver T. Keppler: HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor. Cell Host & Microbe 5, 285-297, March 19, 2009. DOI 10.1016/j.chom.2009.01.009
Heidelberg University Hospital and Medical Faculty:
Internationally recognized patient care, research, and teaching
Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 7,000 employees, training and qualification is an important issue. Every year, around 500,000 patients are treated on an inpatient or outpatient basis in more than 40 clinics and departments with 1,600 beds. Currently, about 3,100 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany.
Source:
PD Dr. med. Oliver T. Keppler
University Hospital Heidelberg
суббота, 25 июня 2011 г.
For The First Time, Experimental Evidence Shows That Hidden Protein Structures Are Essential For Catalysis
An important Brandeis study appearing in the December 3 issue of Nature raises the curtain on the hidden lives of proteins at the atomic level. The study reports that for the first time, researchers used x-ray crystallography and nuclear magnetic resonance (NMR) techniques to directly visualize protein structures essential for catalysis at the rare high-energy state. The study also showed how the motions of these rare, or hidden, structures collectively, directly contribute to enzyme catalysis.
In doing so, the study also suggests new molecular sites for potential drug targets, the cornerstone of rational drug design. Drugs may bind, or dock, to the infrequent high-energy states of target enzymes that have been hidden to traditional structural methods. The thinking is that drugs can be designed by docking algorithms to a collection of protein structures, not just one, providing better bio-molecular targeting.
This study comes in the wake of earlier Brandeis studies aimed at advancing understanding of protein function using pioneering techniques such as NMR. For a long time, scientists viewed proteins more or less as macromolecular wallflowers, venturing out onto the atomic-level dance floor to perform only during catalysis, their active state.
Then, several years ago, Brandeis biophysicist Dorothee Kern reported in Nature that her lab's experiments using NMR also linked protein function to their much rarer high-energy state, in the absence of catalysis. That study helped put to rest the conventional wisdom that proteins actually rest at all.
This Nature study takes Kern's research to the next level, seeing the high-resolution structure of the hidden, high-energy state for the first time. For this success, high -resolution x-ray crystallography was further pushed by analyzing electron density data previously discarded as "noise" and by collecting data at ambient temperature. The protein of interest is human cyclophilin A, an enzyme that is highjacked by the HIV virus to aid its own replication.
But it was thanks to some clever protein design together with dynamic NMR spectroscopy that provided direct experimental evidence that the hidden structures in the high-energy state are in fact essential for catalysis. The researchers revealed what happens when proteins flip from the rare state to a major state in a process called interconversion. If this flip is fast, then the enzyme does its job fast, but if the flip is slow, as in the designer enzyme, then the enzyme operates slowly.
"People always focused on the chemistry - accelerating the reaction through catalyzing the chemical step of the substrates. What we've shown is that protein dynamics is as important as the chemical step," said Kern, a Howard Hughes Medical Institute Investigator. "Basically, all the steps need to be choreographed just right, like steps for a beautiful dancer. An enzyme can only function well with the perfect choreography of all the components."
Said Kern: "We now can show directly that the higher energy states are always there and that these hidden, rare states are absolutely essential for protein function."
Source: Laura Gardner
Brandeis University
In doing so, the study also suggests new molecular sites for potential drug targets, the cornerstone of rational drug design. Drugs may bind, or dock, to the infrequent high-energy states of target enzymes that have been hidden to traditional structural methods. The thinking is that drugs can be designed by docking algorithms to a collection of protein structures, not just one, providing better bio-molecular targeting.
This study comes in the wake of earlier Brandeis studies aimed at advancing understanding of protein function using pioneering techniques such as NMR. For a long time, scientists viewed proteins more or less as macromolecular wallflowers, venturing out onto the atomic-level dance floor to perform only during catalysis, their active state.
Then, several years ago, Brandeis biophysicist Dorothee Kern reported in Nature that her lab's experiments using NMR also linked protein function to their much rarer high-energy state, in the absence of catalysis. That study helped put to rest the conventional wisdom that proteins actually rest at all.
This Nature study takes Kern's research to the next level, seeing the high-resolution structure of the hidden, high-energy state for the first time. For this success, high -resolution x-ray crystallography was further pushed by analyzing electron density data previously discarded as "noise" and by collecting data at ambient temperature. The protein of interest is human cyclophilin A, an enzyme that is highjacked by the HIV virus to aid its own replication.
But it was thanks to some clever protein design together with dynamic NMR spectroscopy that provided direct experimental evidence that the hidden structures in the high-energy state are in fact essential for catalysis. The researchers revealed what happens when proteins flip from the rare state to a major state in a process called interconversion. If this flip is fast, then the enzyme does its job fast, but if the flip is slow, as in the designer enzyme, then the enzyme operates slowly.
"People always focused on the chemistry - accelerating the reaction through catalyzing the chemical step of the substrates. What we've shown is that protein dynamics is as important as the chemical step," said Kern, a Howard Hughes Medical Institute Investigator. "Basically, all the steps need to be choreographed just right, like steps for a beautiful dancer. An enzyme can only function well with the perfect choreography of all the components."
Said Kern: "We now can show directly that the higher energy states are always there and that these hidden, rare states are absolutely essential for protein function."
Source: Laura Gardner
Brandeis University
пятница, 24 июня 2011 г.
Researcher Uncovers Protein's Role In Cell Division
A Florida State University researcher has identified the important role that a key protein plays in cell division, and that discovery could lead to a greater understanding of stem cells.
Timothy L. Megraw, an associate professor in the College of Medicine, has outlined his findings in the cover story of the June 15 issue of Developmental Cell. The article, "CDK5RAP2 Regulates Centriole Engagement and Cohesion in Mice," was co-authored by researchers from the University of Texas Southwestern Medical Center at Dallas and the University of North Texas.
In August, Megraw received a four-year, $1.2 million grant from the National Institutes of Health to explore the role of centrosomes and cilia in cell division and their connections to human disease.
One long-term goal of Megraw's research has been to discover which parts of the cell play which roles in cell division. The centrosome is an important player. When a cell is ready to divide, it typically has two centrosomes, each containing a "mother and daughter" pair of centrioles tightly connected to each other, or "engaged."
"Two is important," Megraw said, "because you divide your genetic material into two equal sets. Each of these centriole pairs organizes the cytoskeletal machinery that pulls the chromosomes apart. So you don't want there to be more than two, because then you run the risk of unequal separation of the chromosomes."
The centrioles are supposed to replicate only once during the cell cycle. What keeps them from replicating more often was discovered a few years ago, Megraw said, when researchers identified mother-daughter engagement as the key. Once those two become disengaged, it acts as the "licensing" step, in effect giving the centrioles permission to replicate.
Unknown until now, Megraw said, was what regulated those centrioles to remain engaged until the proper time, to prevent excess replication. He suspected that the protein CDK5RAP2 was at least partly responsible. His team tested the protein's role using a mutant mouse in which the protein was "knocked out" and not functioning. These researchers looked for any effects on engagement and "cohesion," in which centriole pairs are tethered by fibers.
They noted in the mutant mouse that engagement and cohesion did not occur in their typical orderly fashion and that centrioles were more numerous and often single rather than paired. The amplified centrioles assembled multipolar spindles, a potential hazard for chromosomal stability. The researchers concluded that CDK5RAP2 is required to maintain centriole engagement and cohesion, thereby restricting centriole replication.
They are looking at how this discovery might apply to the human brain.
"The two mouse mutants we made mimic the two known mutations in humans in CDK5RAP2 which has another name, MCPH3, in humans," Megraw said. "The disease associated with that is a small brain.
"Our next step is to look at the brains of the mice and try to determine what's wrong. We think it's the stem cells that the progenitors that give rise to all the neurons in the brain are dying early or changing from a progenitor into a neuron too early."
Another gene called myomegalin might be functionally redundant to CDK5RAP2, Megraw said, adding, "Our goal is to knock that out, too."
The research his lab has done might also be applicable to cancer drugs for humans, he said. Centrosomes organize microtubules, which are structures in the cell that many important anti-cancer drugs target.
"The amplified centrioles and multipolar spindles suggest that the mutant mice may be more susceptible to developing cancers," Megraw said. "We are in a position to test this with our new mouse models."
College of Medicine student Zach Folzenlogen created the cover design for this issue of Developmental Cell.
Source: The Florida State University
Timothy L. Megraw, an associate professor in the College of Medicine, has outlined his findings in the cover story of the June 15 issue of Developmental Cell. The article, "CDK5RAP2 Regulates Centriole Engagement and Cohesion in Mice," was co-authored by researchers from the University of Texas Southwestern Medical Center at Dallas and the University of North Texas.
In August, Megraw received a four-year, $1.2 million grant from the National Institutes of Health to explore the role of centrosomes and cilia in cell division and their connections to human disease.
One long-term goal of Megraw's research has been to discover which parts of the cell play which roles in cell division. The centrosome is an important player. When a cell is ready to divide, it typically has two centrosomes, each containing a "mother and daughter" pair of centrioles tightly connected to each other, or "engaged."
"Two is important," Megraw said, "because you divide your genetic material into two equal sets. Each of these centriole pairs organizes the cytoskeletal machinery that pulls the chromosomes apart. So you don't want there to be more than two, because then you run the risk of unequal separation of the chromosomes."
The centrioles are supposed to replicate only once during the cell cycle. What keeps them from replicating more often was discovered a few years ago, Megraw said, when researchers identified mother-daughter engagement as the key. Once those two become disengaged, it acts as the "licensing" step, in effect giving the centrioles permission to replicate.
Unknown until now, Megraw said, was what regulated those centrioles to remain engaged until the proper time, to prevent excess replication. He suspected that the protein CDK5RAP2 was at least partly responsible. His team tested the protein's role using a mutant mouse in which the protein was "knocked out" and not functioning. These researchers looked for any effects on engagement and "cohesion," in which centriole pairs are tethered by fibers.
They noted in the mutant mouse that engagement and cohesion did not occur in their typical orderly fashion and that centrioles were more numerous and often single rather than paired. The amplified centrioles assembled multipolar spindles, a potential hazard for chromosomal stability. The researchers concluded that CDK5RAP2 is required to maintain centriole engagement and cohesion, thereby restricting centriole replication.
They are looking at how this discovery might apply to the human brain.
"The two mouse mutants we made mimic the two known mutations in humans in CDK5RAP2 which has another name, MCPH3, in humans," Megraw said. "The disease associated with that is a small brain.
"Our next step is to look at the brains of the mice and try to determine what's wrong. We think it's the stem cells that the progenitors that give rise to all the neurons in the brain are dying early or changing from a progenitor into a neuron too early."
Another gene called myomegalin might be functionally redundant to CDK5RAP2, Megraw said, adding, "Our goal is to knock that out, too."
The research his lab has done might also be applicable to cancer drugs for humans, he said. Centrosomes organize microtubules, which are structures in the cell that many important anti-cancer drugs target.
"The amplified centrioles and multipolar spindles suggest that the mutant mice may be more susceptible to developing cancers," Megraw said. "We are in a position to test this with our new mouse models."
College of Medicine student Zach Folzenlogen created the cover design for this issue of Developmental Cell.
Source: The Florida State University
четверг, 23 июня 2011 г.
Harnessing plants to efficiently produce biomass for energy production, chemicals, materials for pharmaceuticals, and other uses -
Ames Laboratory researchers explore new frontier of metabolomics
The biotech field of genomics gives scientists genetic roadmaps to link certain genes to diseases. The subsequent study of proteins produced by certain genes spawned the field of proteomics.
Now, a group of researchers at the U.S. Department of Energy's Ames Laboratory at Iowa State University will use $1.02 million in DOE start-up funding to begin understanding the chemical processes that take place within the cells of plants. This new field, called metabolomics, could result in harnessing plants to efficiently produce biomass for energy production, chemicals and materials for industry or pharmaceuticals, and untold thousands of other uses.
"We know a lot about the genetic make-up of many plants, but we know very little about the chemical changes that take place within plant cells that eventually produce sugars, fibers or waxes," said Ed Yeung, program director of Chemical and Biological Sciences at Ames Lab and principal investigator on the project. "If we can understand metabolism, then ideally, all the materials a plant produces can be controlled."
The project, "Mass Spectrometric Imaging of Plant Metabolites," combines the analytical chemistry expertise of Ames Laboratory with the strength of ISU's Plant Sciences Institute. Yeung, who is also a distinguished professor of chemistry at ISU, is internationally recognized for his work in developing separation and detection technologies, having won four R&D 100 awards.
Also working on the project are Sam Houk, an Ames Lab senior chemist who specializes in identifying trace elements using inductively couple plasma-mass spectrometry, and associate scientist and ISU chemistry professor Ethan Badman, who specializes in mass spectrometry and gas-phase methods of analysis for biological molecules. Rounding out the team is Basil Nikolau, Director of the Plant Sciences Institute's Center for Designer Crops and a specialist in biochemistry and functional genomics of plant metabolism.
Funding from the Chemical Sciences, Geosciences and Biosciences Division of the DOE's Office of Basic Energy Sciences provides $340,000 for operation and equipment this year and another $680,000 in 2006. Additional money is expected in 2007 and could continue if the program receives good marks during a peer review scheduled for 2008.
Before they can study the chemical makeup within plant cells, the team must construct new analytical instruments capable of identifying molecules in such minute quantities.
"Developing the instrumentation is a large part of the proposal and we're building a special, high-resolution mass spectrometer," Yeung said, "because there's nothing available commercially that meets our needs." He added that the equipment will be housed in the Roy J. Carver Co-Laboratory on the ISU campus.
Mass spectrometry works by measuring the mass of individual ions - molecules that have been electrically charged. Plant material is ionized into a gas, sorted in an analyzer chamber according to the mass-to-charge ratios, and collected by an ion detector. The detector converts ion flux into a proportional electrical current. Finally, the magnitude of the electrical signals is recorded and plotted as a mass spectrum.
The ability to sort and detect these ions at cellular-scale quantities is where the team hopes to fine-tune the instrumentation.
Once the equipment is ready, the team will look at the chemical content in the cells of Arabidopsis thaliana, a small flowering plant that is widely used as a model organism in plant biology. Arabidopsis is a member of the mustard (Brassicaceae) family, which includes cultivated species such as cabbage and radish.
"Arabidopsis is not a major crop like corn and soybeans," Yeung said, "but because so much is already known about it genetically, we can hopefully begin to draw correlations between the chemical and genetic makeup. We hope that such fundamental research will be applicable to other plants as well."
Ames Laboratory is a DOE Office of Science research facility operated by Iowa State University. The Lab conducts research into various areas of national concern, including energy resources, high-speed computer design, environmental cleanup and restoration, and the synthesis and study of new materials.
Kerry Gibson
kgibsonameslab
515-294-1405
DOE/Ames Laboratory
external.ameslab
The biotech field of genomics gives scientists genetic roadmaps to link certain genes to diseases. The subsequent study of proteins produced by certain genes spawned the field of proteomics.
Now, a group of researchers at the U.S. Department of Energy's Ames Laboratory at Iowa State University will use $1.02 million in DOE start-up funding to begin understanding the chemical processes that take place within the cells of plants. This new field, called metabolomics, could result in harnessing plants to efficiently produce biomass for energy production, chemicals and materials for industry or pharmaceuticals, and untold thousands of other uses.
"We know a lot about the genetic make-up of many plants, but we know very little about the chemical changes that take place within plant cells that eventually produce sugars, fibers or waxes," said Ed Yeung, program director of Chemical and Biological Sciences at Ames Lab and principal investigator on the project. "If we can understand metabolism, then ideally, all the materials a plant produces can be controlled."
The project, "Mass Spectrometric Imaging of Plant Metabolites," combines the analytical chemistry expertise of Ames Laboratory with the strength of ISU's Plant Sciences Institute. Yeung, who is also a distinguished professor of chemistry at ISU, is internationally recognized for his work in developing separation and detection technologies, having won four R&D 100 awards.
Also working on the project are Sam Houk, an Ames Lab senior chemist who specializes in identifying trace elements using inductively couple plasma-mass spectrometry, and associate scientist and ISU chemistry professor Ethan Badman, who specializes in mass spectrometry and gas-phase methods of analysis for biological molecules. Rounding out the team is Basil Nikolau, Director of the Plant Sciences Institute's Center for Designer Crops and a specialist in biochemistry and functional genomics of plant metabolism.
Funding from the Chemical Sciences, Geosciences and Biosciences Division of the DOE's Office of Basic Energy Sciences provides $340,000 for operation and equipment this year and another $680,000 in 2006. Additional money is expected in 2007 and could continue if the program receives good marks during a peer review scheduled for 2008.
Before they can study the chemical makeup within plant cells, the team must construct new analytical instruments capable of identifying molecules in such minute quantities.
"Developing the instrumentation is a large part of the proposal and we're building a special, high-resolution mass spectrometer," Yeung said, "because there's nothing available commercially that meets our needs." He added that the equipment will be housed in the Roy J. Carver Co-Laboratory on the ISU campus.
Mass spectrometry works by measuring the mass of individual ions - molecules that have been electrically charged. Plant material is ionized into a gas, sorted in an analyzer chamber according to the mass-to-charge ratios, and collected by an ion detector. The detector converts ion flux into a proportional electrical current. Finally, the magnitude of the electrical signals is recorded and plotted as a mass spectrum.
The ability to sort and detect these ions at cellular-scale quantities is where the team hopes to fine-tune the instrumentation.
Once the equipment is ready, the team will look at the chemical content in the cells of Arabidopsis thaliana, a small flowering plant that is widely used as a model organism in plant biology. Arabidopsis is a member of the mustard (Brassicaceae) family, which includes cultivated species such as cabbage and radish.
"Arabidopsis is not a major crop like corn and soybeans," Yeung said, "but because so much is already known about it genetically, we can hopefully begin to draw correlations between the chemical and genetic makeup. We hope that such fundamental research will be applicable to other plants as well."
Ames Laboratory is a DOE Office of Science research facility operated by Iowa State University. The Lab conducts research into various areas of national concern, including energy resources, high-speed computer design, environmental cleanup and restoration, and the synthesis and study of new materials.
Kerry Gibson
kgibsonameslab
515-294-1405
DOE/Ames Laboratory
external.ameslab
среда, 22 июня 2011 г.
Researcher journeys to the centre of the cell, University of Queensland
The discovery of a fundamental new route into cells may lead to new methods of drug delivery and to a better
understanding of viral infection.
Researchers from The University of Queensland's Institute for Molecular Bioscience (IMB), and the Centre for Microscopy and
Microanalysis used electron microscopy to uncover new structures, 100,000th of a mm in size, which are involved in the very
first step of particle and nutrient uptake into cells.
Cells require a constant flux of nutrients and other chemicals for survival and it is vitally important to understand how
these materials reach the inside of the cell.
IMB's Professor Rob Parton said that endocytosis, the process of regulated uptake by the cell was vitally important, occurred
continuously, and a cell virtually ate its entire skin every 30 minutes.
"Endocytosis can be hijacked by viruses to enter the cell and so understanding this process can provide avenues to stop some
viral infections. In addition, endocytosis can be used by researchers aiming to deliver drugs into cells," he said.
"This new pathway was long suspected, however our work was the first to conclusively prove its existence and to identify the
cellular structures involved.
"The discovery of this pathway presents unexplored avenues for the development of new drugs to fight certain viral
infections, as well as opening up new possibilities for drug delivery or gene therapy.
"In addition we believe this pathway is extremely important in evolutionary terms and will provide important information
about the development of complex organisms," Professor Parton said.
He said the next step was to determine the proteins and genes involved in the process.
Professor Parton also acknowledged the contributions of his co-workers, in particular Matthew Kirkham (PhD student) and
Akikazu Fujita (visiting scientist) who jointly conducted the majority of the work at the University of Queensland, as well
as his overseas collaborators in India, the United States, and Germany.
Professor Parton's work was published in the internationally recognised Journal of Cell Biology.
The IMB is at the forefront of the drive to understand the programming and regulation of mammalian growth and development,
which will significantly impact on human health through new therapeutics and diagnostics.
Media: For more information, contact Rob Parton (61-733-462-032) or Russell Griggs (61-733-462-134).
Contact: Russell Griggs
61-733-462-134
Research Australia
researchaustralia.au
understanding of viral infection.
Researchers from The University of Queensland's Institute for Molecular Bioscience (IMB), and the Centre for Microscopy and
Microanalysis used electron microscopy to uncover new structures, 100,000th of a mm in size, which are involved in the very
first step of particle and nutrient uptake into cells.
Cells require a constant flux of nutrients and other chemicals for survival and it is vitally important to understand how
these materials reach the inside of the cell.
IMB's Professor Rob Parton said that endocytosis, the process of regulated uptake by the cell was vitally important, occurred
continuously, and a cell virtually ate its entire skin every 30 minutes.
"Endocytosis can be hijacked by viruses to enter the cell and so understanding this process can provide avenues to stop some
viral infections. In addition, endocytosis can be used by researchers aiming to deliver drugs into cells," he said.
"This new pathway was long suspected, however our work was the first to conclusively prove its existence and to identify the
cellular structures involved.
"The discovery of this pathway presents unexplored avenues for the development of new drugs to fight certain viral
infections, as well as opening up new possibilities for drug delivery or gene therapy.
"In addition we believe this pathway is extremely important in evolutionary terms and will provide important information
about the development of complex organisms," Professor Parton said.
He said the next step was to determine the proteins and genes involved in the process.
Professor Parton also acknowledged the contributions of his co-workers, in particular Matthew Kirkham (PhD student) and
Akikazu Fujita (visiting scientist) who jointly conducted the majority of the work at the University of Queensland, as well
as his overseas collaborators in India, the United States, and Germany.
Professor Parton's work was published in the internationally recognised Journal of Cell Biology.
The IMB is at the forefront of the drive to understand the programming and regulation of mammalian growth and development,
which will significantly impact on human health through new therapeutics and diagnostics.
Media: For more information, contact Rob Parton (61-733-462-032) or Russell Griggs (61-733-462-134).
Contact: Russell Griggs
61-733-462-134
Research Australia
researchaustralia.au
вторник, 21 июня 2011 г.
E.coli 0157 And Salmonella: Understanding, Combating Foodborne Pathogens
Understanding the ecology of two dangerous foodborne pathogens and devising ways to combat them is a big job. That's why Kansas State University has a team of seven researchers and six collaborators taking on E. coli 0157 and salmonella.
"It's becoming more and more difficult to study these pathogens because you have to be a jack of all trades," said T.G. Nagaraja, professor of diagnostic medicine pathobiology at K-State's College of Veterinary Medicine.
Nagaraja leads a research group that includes epidemiologists, molecular biologists, production animal medicine experts and feedlot nutritionists.
For the past five years, Nagaraja has been leading the team on an E. coli 0157 research project that goes back more than a decade at K-State. E. coli 0157 doesn't cause problems for livestock, but it's zoonotic -- that is, it can be passed on to humans through the food supply.
"Our goals are fairly simple," Nagaraja said. "We want to understand the ecology of E. coli 0157 in cattle and come up with practical, on-farm intervention strategies."
The rest of the research team includes Sanjeev Narayanan, assistant professor of pathology and molecular biology; Richard Oberst, professor of microbiology; David Renter, assistant professor in epidemiology; Mike Sanderson, associate professor of epidemiology and production animal medicine; Daniel Thomson, assistant professor of feedlot production medicine; and Ludek Zurek, associate professor of entomology.
Collaborators include K-State's Mike Apley, associate professor of production animal medicine; Jim Drouillard, professor of feedlot nutrition; Larry Hollis, professor in animal sciences and industry; Justin Kastner, assistant professor of food safety and security; and Abby Nutsch, assistant professor of food microbiology; as well as Kelly Lechtenberg, director of Midwest Veterinary Research Inc. in Oakland, Neb.
The research team is working to answer questions like why some cattle have E. coli 0157 and some don't, and why some shed the bacteria for a longer time or at higher levels than others.
The K-State researchers also want to understand why the presence of 0157 is higher during some months than in others, and why animals under stress shed more of the bacteria than other animals.
"If we find out answers to these questions, we can come up with intervention strategies," Nagaraja said. "The first part of the research is to look at the ecology, and the second part is to develop tests and practical intervention strategies."
For instance, Thomson is doing research with a company in Minnesota on a vaccine with antibodies that prevent the bacteria from getting iron, which they need to live. All three studies have shown a reduction in the prevalence of 0157 when the vaccine is used, Nagaraja said.
He also said that researchers are looking at what changes they could make in cattle diets that would make the animals' digestive systems less hospitable to 0157. Because the bacteria seem to congregate in the hindgut, Nagaraja said feeding cattle a diet that will reach the hindgut and produce acid will be effective in killing 0157. He also said that probiotics -- beneficial bacteria, like what humans can get though eating yogurt -- can reduce 0157 because they out compete the bacteria for resources.
Salmonella, one of the most common causes of gastroenteritis and which is spread through contaminated ground beef and manure-fertilized produce, also harms livestock. It causes bloody diarrhea in feedlot cattle and causes dairy cattle to abort. Renter's work centers on finding out why feedlot cattle that are being treated for other infections may show a higher rate of salmonella than healthy cattle. To find out the serotype of the salmonella, veterinarians and researchers have to send samples to a laboratory in Iowa. Narayanan is working to develop a rapid, molecular-based testing method that is more accessible.
Nagaraja said that in the future the research team will pursue the goal of eliminating 0157 and salmonella. Although 0157 also is spread by grain-eating birds that carry the bacteria from one feedlot to another, it poses less of a challenge than salmonella. Nagaraja said that rodents and other animals that live in barns carry salmonella, so the research team hopes to at least reduce its prevalence. The research team also is studying antimicrobial resistance with the hopes of preventing foodborne pathogens from becoming more dangerous to humans and animals.
"Salmonella is notorious for becoming resistant to multiple antibiotics," Nagaraja said. "Also, it can transfer the genes that cause antibacterial resistance to other bacteria. Our primary objective is to develop a synergistic program to evaluate the role of the cattle industry on the prevalence, amplification and spread of antimicrobial resistance."
Source: T.G. Nagaraja
Kansas State University
"It's becoming more and more difficult to study these pathogens because you have to be a jack of all trades," said T.G. Nagaraja, professor of diagnostic medicine pathobiology at K-State's College of Veterinary Medicine.
Nagaraja leads a research group that includes epidemiologists, molecular biologists, production animal medicine experts and feedlot nutritionists.
For the past five years, Nagaraja has been leading the team on an E. coli 0157 research project that goes back more than a decade at K-State. E. coli 0157 doesn't cause problems for livestock, but it's zoonotic -- that is, it can be passed on to humans through the food supply.
"Our goals are fairly simple," Nagaraja said. "We want to understand the ecology of E. coli 0157 in cattle and come up with practical, on-farm intervention strategies."
The rest of the research team includes Sanjeev Narayanan, assistant professor of pathology and molecular biology; Richard Oberst, professor of microbiology; David Renter, assistant professor in epidemiology; Mike Sanderson, associate professor of epidemiology and production animal medicine; Daniel Thomson, assistant professor of feedlot production medicine; and Ludek Zurek, associate professor of entomology.
Collaborators include K-State's Mike Apley, associate professor of production animal medicine; Jim Drouillard, professor of feedlot nutrition; Larry Hollis, professor in animal sciences and industry; Justin Kastner, assistant professor of food safety and security; and Abby Nutsch, assistant professor of food microbiology; as well as Kelly Lechtenberg, director of Midwest Veterinary Research Inc. in Oakland, Neb.
The research team is working to answer questions like why some cattle have E. coli 0157 and some don't, and why some shed the bacteria for a longer time or at higher levels than others.
The K-State researchers also want to understand why the presence of 0157 is higher during some months than in others, and why animals under stress shed more of the bacteria than other animals.
"If we find out answers to these questions, we can come up with intervention strategies," Nagaraja said. "The first part of the research is to look at the ecology, and the second part is to develop tests and practical intervention strategies."
For instance, Thomson is doing research with a company in Minnesota on a vaccine with antibodies that prevent the bacteria from getting iron, which they need to live. All three studies have shown a reduction in the prevalence of 0157 when the vaccine is used, Nagaraja said.
He also said that researchers are looking at what changes they could make in cattle diets that would make the animals' digestive systems less hospitable to 0157. Because the bacteria seem to congregate in the hindgut, Nagaraja said feeding cattle a diet that will reach the hindgut and produce acid will be effective in killing 0157. He also said that probiotics -- beneficial bacteria, like what humans can get though eating yogurt -- can reduce 0157 because they out compete the bacteria for resources.
Salmonella, one of the most common causes of gastroenteritis and which is spread through contaminated ground beef and manure-fertilized produce, also harms livestock. It causes bloody diarrhea in feedlot cattle and causes dairy cattle to abort. Renter's work centers on finding out why feedlot cattle that are being treated for other infections may show a higher rate of salmonella than healthy cattle. To find out the serotype of the salmonella, veterinarians and researchers have to send samples to a laboratory in Iowa. Narayanan is working to develop a rapid, molecular-based testing method that is more accessible.
Nagaraja said that in the future the research team will pursue the goal of eliminating 0157 and salmonella. Although 0157 also is spread by grain-eating birds that carry the bacteria from one feedlot to another, it poses less of a challenge than salmonella. Nagaraja said that rodents and other animals that live in barns carry salmonella, so the research team hopes to at least reduce its prevalence. The research team also is studying antimicrobial resistance with the hopes of preventing foodborne pathogens from becoming more dangerous to humans and animals.
"Salmonella is notorious for becoming resistant to multiple antibiotics," Nagaraja said. "Also, it can transfer the genes that cause antibacterial resistance to other bacteria. Our primary objective is to develop a synergistic program to evaluate the role of the cattle industry on the prevalence, amplification and spread of antimicrobial resistance."
Source: T.G. Nagaraja
Kansas State University
понедельник, 20 июня 2011 г.
Rice To Host Year Of Nano, Buckyball Discovery Conference
The biggest names in nanotechnology are preparing to gather this fall at Rice University, and everyone is welcome to join them.
Registration is open for Year of Nano events to be held Oct. 10-13 in honor of the 25th anniversary of the Nobel Prize-winning discovery of the carbon 60 molecule, the buckminsterfullerene, at Rice.
The Richard E. Smalley Institute for Nanoscale Science and Technology, the world's first nanotechnology center when it opened in 1991, will bring top scientists to Rice for the Buckyball Discovery Conference, a three-day event that begins Oct. 11 and will take a comprehensive look at the past, present and future of nanotechnology.
The conference will incorporate the annual T.T. Chao Symposium on Innovation, which brings together established and emerging leaders in the technical, entrepreneurial and policy arenas to think about how Houston can address society's needs in the 21st century.
An interactive discussion about the discovery of the buckyball moderated by Tom Tritton, president of the Chemical Heritage Foundation, will kick off the event. Nobel laureates Robert Curl, Rice's University Professor Emeritus and Kenneth S. Pitzer-Schlumberger Professor Emeritus of Natural Sciences; Sir Harold Kroto, a professor at the University of Sussex at the time of the find and now at Florida State University; and former Rice graduate students James Heath and Sean O'Brien will reminisce about their groundbreaking discovery and the many years they spent defending it, what their work has meant for science and where they see nanotechnology headed. They will talk about working with their Rice colleague and fellow laureate, the late Rick Smalley, and answer audience questions.
Following the Nobel session, Ray Johnson, chief technology officer at Lockheed Martin, will offer the first lunchtime keynote address. Heath, now a professor of chemistry at the California Institute of Technology, will deliver Tuesday's keynote.
Eight of the world's renowned carbon nanotechnologists will discuss current research and development as well as the future of nanotechnology. They include Phaedon Avouris, Marvin Cohen, Hongjie Dai, Millie Dresselhaus, Morinobu Endo, Andre Geim, Andreas Hirsch and Donald Huffman. Breakout sessions will delve into applications of nanotechnology and the obstacles it faces in areas that include environmental health and safety, energy, health, aerospace and materials.
Jim Kohlhaas, vice president for energy initiatives, corporate engineering and technology at Lockheed Martin, and Horst Adams, general manager of the metal branch and vice president of future technologies at Bayer MaterialScience, will lead two of the breakout sessions.
The conference is free, but participants must register and pay for meals and special events.
The "Week of Nano" will also feature a Bucky "Ball" Celebration at Rice on the evening of Oct. 11. It will include the presentation of the National Historic Chemical Landmark designation, facility tours, nanotechnology demos and memorabilia, as well as food and drinks. On Oct. 10, friends and fans of nano research at Rice will celebrate at the 10-10-10 Gala.
Lockheed Martin is the primary sponsor of the Year of Nano events. The company partners with the Richard E. Smalley Institute for Nanoscale Science and Technology in the Lockheed Martin Advanced Nanotechnology Center of Excellence at Rice, aka LANCER, through which researchers in academia tackle the high-tech industry's toughest problems.
For information about the Year of Nano, the conference and associated events, click here.
Source:
David Ruth
Rice University
Registration is open for Year of Nano events to be held Oct. 10-13 in honor of the 25th anniversary of the Nobel Prize-winning discovery of the carbon 60 molecule, the buckminsterfullerene, at Rice.
The Richard E. Smalley Institute for Nanoscale Science and Technology, the world's first nanotechnology center when it opened in 1991, will bring top scientists to Rice for the Buckyball Discovery Conference, a three-day event that begins Oct. 11 and will take a comprehensive look at the past, present and future of nanotechnology.
The conference will incorporate the annual T.T. Chao Symposium on Innovation, which brings together established and emerging leaders in the technical, entrepreneurial and policy arenas to think about how Houston can address society's needs in the 21st century.
An interactive discussion about the discovery of the buckyball moderated by Tom Tritton, president of the Chemical Heritage Foundation, will kick off the event. Nobel laureates Robert Curl, Rice's University Professor Emeritus and Kenneth S. Pitzer-Schlumberger Professor Emeritus of Natural Sciences; Sir Harold Kroto, a professor at the University of Sussex at the time of the find and now at Florida State University; and former Rice graduate students James Heath and Sean O'Brien will reminisce about their groundbreaking discovery and the many years they spent defending it, what their work has meant for science and where they see nanotechnology headed. They will talk about working with their Rice colleague and fellow laureate, the late Rick Smalley, and answer audience questions.
Following the Nobel session, Ray Johnson, chief technology officer at Lockheed Martin, will offer the first lunchtime keynote address. Heath, now a professor of chemistry at the California Institute of Technology, will deliver Tuesday's keynote.
Eight of the world's renowned carbon nanotechnologists will discuss current research and development as well as the future of nanotechnology. They include Phaedon Avouris, Marvin Cohen, Hongjie Dai, Millie Dresselhaus, Morinobu Endo, Andre Geim, Andreas Hirsch and Donald Huffman. Breakout sessions will delve into applications of nanotechnology and the obstacles it faces in areas that include environmental health and safety, energy, health, aerospace and materials.
Jim Kohlhaas, vice president for energy initiatives, corporate engineering and technology at Lockheed Martin, and Horst Adams, general manager of the metal branch and vice president of future technologies at Bayer MaterialScience, will lead two of the breakout sessions.
The conference is free, but participants must register and pay for meals and special events.
The "Week of Nano" will also feature a Bucky "Ball" Celebration at Rice on the evening of Oct. 11. It will include the presentation of the National Historic Chemical Landmark designation, facility tours, nanotechnology demos and memorabilia, as well as food and drinks. On Oct. 10, friends and fans of nano research at Rice will celebrate at the 10-10-10 Gala.
Lockheed Martin is the primary sponsor of the Year of Nano events. The company partners with the Richard E. Smalley Institute for Nanoscale Science and Technology in the Lockheed Martin Advanced Nanotechnology Center of Excellence at Rice, aka LANCER, through which researchers in academia tackle the high-tech industry's toughest problems.
For information about the Year of Nano, the conference and associated events, click here.
Source:
David Ruth
Rice University
воскресенье, 19 июня 2011 г.
Tumor-Inhibiting Protein Could Be Effective In Treating Leukemia
Angiocidin, a tumor-inhibiting novel protein discovered by Temple University researchers, may also have a role as a new therapeutic application in treating leukemia, according to a study by the researchers.
The study, "The Novel Angiogenic Inhibitor, Angiocidin, Induces Differentiation of Monocytes to Macropahges," was published in the July 15 issue of the journal Cancer Research (cancerres.aacrjournals/future/68.14.shtml). The research was done by Temple biology doctoral student Anita Gaurnier-Hausser under the direction of George Tuszynski, a professor of neuroscience in Temple's School of Medicine and a professor of biology in Temple's College of Science and Technology.
"Angiocidin is a protein that has a lot of anti-cancer activity and inhibits angiogenesis, a physiological process involving the growth of new blood vessels from pre-existing vessels, which is a fundamental step in the transition of tumors from a dormant state to a malignant state," said Tuszynski, who discovered the protein.
Tuszynski said that over the years, the researchers had looked at the protein's effect on solid tumors like breast cancer, prostate cancer and colon cancer.
"All of these cancers are inhibited by Angiocidin by virtue of the fact that this protein inhibits vascularization or the formation of new vessels," he said. "We decided we wanted to look to see if Angiocidin had any effect on hematologic malignancy, and we chose leukemia."
Tuszynski said leukemia cells arise from monocytes, a specific white blood cell that is a part of the human body's immune system that protects against bloodborne pathogens and moves quickly to sites of infection. As monocytes enter tissue, they undergo a series of changes to become macrophages.
When the researchers treated the leukemia cells, "our molecule was able to induce a differentiation of these monocytic leukemia cells into a normal, macrophage-like phenotype," he said.
"This indicates perhaps a new therapeutic application for this protein, that it could differentiate hematologic malignancies into a normal-like state, allowing then for chemotherapy because normal cells are susceptible to chemotherapy treatment," said Tuszynski, who is also a member of the Sol Sherry Thrombosis Research Center in Temple's School of Medicine.
He added, however, that Angiocidin must remain present with the differentiated cells or they will revert back to their leukemia phenotype. "We haven't repaired the genetic abnormality in the cell, but what we have done is push them into a more normal phenotype that could then be treated more easily."
Tuszynski also said that the research demonstrates the ability of Angiocidin to stimulate the body's immune system by differentiating monocytic cells into macrophages, which function to ingest bacteria and protein debris as part of the immune system.
"We did gene array analysis of the differentiated versus the undifferentiated cells and we discovered that there were many genes characteristic of immune cells that were up-regulated in the differentiated leukemia cells," he said. "That Angiocidin can stimulate differentiation and stimulate the immune system is basically a new activity that we discovered with this protein that we had never really anticipated before."
The research was funded by the National Institutes of Health and Temple University.
Source: Preston M. Moretz
Temple University
The study, "The Novel Angiogenic Inhibitor, Angiocidin, Induces Differentiation of Monocytes to Macropahges," was published in the July 15 issue of the journal Cancer Research (cancerres.aacrjournals/future/68.14.shtml). The research was done by Temple biology doctoral student Anita Gaurnier-Hausser under the direction of George Tuszynski, a professor of neuroscience in Temple's School of Medicine and a professor of biology in Temple's College of Science and Technology.
"Angiocidin is a protein that has a lot of anti-cancer activity and inhibits angiogenesis, a physiological process involving the growth of new blood vessels from pre-existing vessels, which is a fundamental step in the transition of tumors from a dormant state to a malignant state," said Tuszynski, who discovered the protein.
Tuszynski said that over the years, the researchers had looked at the protein's effect on solid tumors like breast cancer, prostate cancer and colon cancer.
"All of these cancers are inhibited by Angiocidin by virtue of the fact that this protein inhibits vascularization or the formation of new vessels," he said. "We decided we wanted to look to see if Angiocidin had any effect on hematologic malignancy, and we chose leukemia."
Tuszynski said leukemia cells arise from monocytes, a specific white blood cell that is a part of the human body's immune system that protects against bloodborne pathogens and moves quickly to sites of infection. As monocytes enter tissue, they undergo a series of changes to become macrophages.
When the researchers treated the leukemia cells, "our molecule was able to induce a differentiation of these monocytic leukemia cells into a normal, macrophage-like phenotype," he said.
"This indicates perhaps a new therapeutic application for this protein, that it could differentiate hematologic malignancies into a normal-like state, allowing then for chemotherapy because normal cells are susceptible to chemotherapy treatment," said Tuszynski, who is also a member of the Sol Sherry Thrombosis Research Center in Temple's School of Medicine.
He added, however, that Angiocidin must remain present with the differentiated cells or they will revert back to their leukemia phenotype. "We haven't repaired the genetic abnormality in the cell, but what we have done is push them into a more normal phenotype that could then be treated more easily."
Tuszynski also said that the research demonstrates the ability of Angiocidin to stimulate the body's immune system by differentiating monocytic cells into macrophages, which function to ingest bacteria and protein debris as part of the immune system.
"We did gene array analysis of the differentiated versus the undifferentiated cells and we discovered that there were many genes characteristic of immune cells that were up-regulated in the differentiated leukemia cells," he said. "That Angiocidin can stimulate differentiation and stimulate the immune system is basically a new activity that we discovered with this protein that we had never really anticipated before."
The research was funded by the National Institutes of Health and Temple University.
Source: Preston M. Moretz
Temple University
суббота, 18 июня 2011 г.
Tugging At Molecules With Optical Tweezers
MIT researchers have developed a novel technique to measure the strength of the bonds between two protein molecules important in cell machinery: Gently tugging them apart with light beams.
"It's really giving us a molecular-level picture of what's going on," said Matthew Lang, an assistant professor of biological and mechanical engineering and senior author of a paper on the work appearing in the June 30 advanced online issue of the Proceedings of the National Academy of Sciences.
Last fall, Lang and others demonstrated that light beams could be used to pick up and move individual cells around the surface of a microchip.
Now they have applied the optical tweezers to measuring protein microarchitectures, allowing them to study the forces that give cells their structure and the ability to move.
The researchers focused on proteins that bind to actin filaments, an important component of the cytoskeleton. Depending on the arrangement and interaction of actin filaments, they can provide structural support, help the cell crawl across a surface or sustain a load (in muscle cells).
"We're trying to understand how nature engineered these molecular linkages to use in different ways," said Lang.
Actin filaments are most commonly found either bonded or crosslinked by a much smaller actin binding protein.
The researchers studied the interactions between the proteins by pinning one actin filament to a surface and controlling the motion of the second one with a beam of light. As the researchers tug on a bead attached to the second filament, the bond mediated by the actin-binding protein eventually breaks.
With this technique, the researchers can get a precise measurement of the force holding the proteins together, which is on the order of piconewtons (10^-12 newtons).
The same technique could be used to investigate many of the other hundreds of protein interactions that occur in the cytoskeleton, said Lang.
Lead author of the paper is Jorge Ferrer, a recent PhD recipient in biological engineering. Other MIT authors of the paper are Hyungsuk Lee and Benjamin Pelz, graduate students in mechanical engineering; and Roger Kamm, the Germeshausen Professor of Mechanical Engineering and Biological Engineering.
Jiong Chen of Stony Brook University and Fumihiko Nakamura of Harvard Medical School are also authors of the paper.
The research was funded by the Nicholas Hobson Wheeles Jr. Fellowship, the W.M. Keck Foundation, and the Westaway Research Fund.
By Anne Trafton, MIT News Office
Source: Teresa Herbert
Massachusetts Institute of Technology
"It's really giving us a molecular-level picture of what's going on," said Matthew Lang, an assistant professor of biological and mechanical engineering and senior author of a paper on the work appearing in the June 30 advanced online issue of the Proceedings of the National Academy of Sciences.
Last fall, Lang and others demonstrated that light beams could be used to pick up and move individual cells around the surface of a microchip.
Now they have applied the optical tweezers to measuring protein microarchitectures, allowing them to study the forces that give cells their structure and the ability to move.
The researchers focused on proteins that bind to actin filaments, an important component of the cytoskeleton. Depending on the arrangement and interaction of actin filaments, they can provide structural support, help the cell crawl across a surface or sustain a load (in muscle cells).
"We're trying to understand how nature engineered these molecular linkages to use in different ways," said Lang.
Actin filaments are most commonly found either bonded or crosslinked by a much smaller actin binding protein.
The researchers studied the interactions between the proteins by pinning one actin filament to a surface and controlling the motion of the second one with a beam of light. As the researchers tug on a bead attached to the second filament, the bond mediated by the actin-binding protein eventually breaks.
With this technique, the researchers can get a precise measurement of the force holding the proteins together, which is on the order of piconewtons (10^-12 newtons).
The same technique could be used to investigate many of the other hundreds of protein interactions that occur in the cytoskeleton, said Lang.
Lead author of the paper is Jorge Ferrer, a recent PhD recipient in biological engineering. Other MIT authors of the paper are Hyungsuk Lee and Benjamin Pelz, graduate students in mechanical engineering; and Roger Kamm, the Germeshausen Professor of Mechanical Engineering and Biological Engineering.
Jiong Chen of Stony Brook University and Fumihiko Nakamura of Harvard Medical School are also authors of the paper.
The research was funded by the Nicholas Hobson Wheeles Jr. Fellowship, the W.M. Keck Foundation, and the Westaway Research Fund.
By Anne Trafton, MIT News Office
Source: Teresa Herbert
Massachusetts Institute of Technology
пятница, 17 июня 2011 г.
Scripps Research Scientists Win $65 Million In New Grants To Reveal Form And Function Of Proteins
Scripps Research Institute scientists have been awarded approximately $65 million in four five-year grants as part of the National Institutes of Health's (NIH) latest round of structural biology funding. The projects will focus on determining the shapes and functions of proteins and protein complexes that are important in biology and medicine.
"The grants are an acknowledgement of The Scripps Research Institute's leadership in the field of structural studies," said Scripps Research President Richard A. Lerner, M.D. "We're looking forward to many more important advances from our scientists thanks to this latest round of support from the NIH."
The four Scripps Research grants are part of the NIH Protein Structure Initiative (PSI), an effort that started in 2000 with the main goal of developing highly efficient methods for solving the structures of many different proteins. The new grants mark the beginning of the effort's third phase, called "PSI:Biology." A key aim of this phase is to apply the high-throughput methods developed during the initiative's first decade to challenging biological problems and systems.
"These awards to Scripps Research represent the key elements of the Protein Structure Initiative - from generating structures and new structure determination methods for particularly challenging proteins to harnessing the power of high-throughput to address important biological problems," said Ward Smith, Ph.D., director of the PSI. "Together, these approaches can significantly advance our understanding of the role proteins play in health and disease."
The Scripps Research grants are:
$37.6 million to a consortium led by Ian A. Wilson, D.Phil., Hansen Professor of Structural Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research.
$5.8 million to a group led by Jamie Williamson, Ph.D., professor, dean of the graduate school, and member of the Skaggs Institute, and Daniel R. Salomon, M.D., associate professor and Medical Director of the Scripps Center for Organ and Cell Transplantation
$16.8 million to a center led by Raymond Stevens, Ph.D., professor in the Departments of Molecular Biology and Chemistry, together with Scripps Research investigators Assistant Professor Vadim Cherezov, Associate Professor Peter Kuhn, Professor Hugh Rosen, and Professor Kurt WГјthrich
$5 million to the Scripps Research portion of a collaboration led by Geoffrey Chang, Ph.D., associate professor and member of the Skaggs Institute, in conjunction with Doug Rees, Howard Hughes Medical Institute investigator and Professor at the California Institute of Technology, and Michael Stowell, associate professor at the University of Colorado. The total for this grant is $11.5 million.
Large-Scale Structure Determination
Building on a decade of success and the solution of more than 1,000 structures, Wilson will continue to lead one of four, long-standing, large-scale PSI centers.
The consortium - called the Joint Center for Structural Genomics (JCSG) and comprising scientists at the University of California, San Diego; Genomics Institute of the Novartis Research Foundation (GNF); Sanford-Burnham Medical Research Institute; and Stanford Synchrotron Radiation Lightsource (SSRL), Stanford University - will continue to operate its pipeline for high-throughput structure determination. Structures that the group plans to tackle over the next five years include challenging targets, such as eukaryotic proteins, as well as protein-protein, protein-RNA, protein-DNA, and other complexes.
One theme of the center's research will be the human "microbiome," the totality of microbes in a defined environment, such as the human digestive tract.
"Interactions of bacteria with the human body are profound and have a significant impact on maintenance of general human health," said Wilson. "In addition, they are associated with obesity, inflammatory diseases, diabetes, and certain cancers, to name but a few disorders."
The center will focus on solving these structures by continuing to hone their highly efficient methods and by conducting collaborative research, including with scientists outside the PSI network.
Biological Problems
The JCSG and other large-scale centers will partner with eight groups of biologists, including one based at Scripps Research, that require the determination of many protein and protein-RNA structures to understand biological processes or a molecule's function.
The Scripps Research center, led by Williamson and Salomon, will focus on better understanding the workings of part of our immune system, which protects us against disease by fending off pathogens such as bacteria, viruses, and tumor cells. The immune system is also a critical determinant of the success or failure of kidney, heart, liver, and bone marrow cell transplants. In particular, the scientists aim to better understand the role of ribonucleoproteins (complexes of RNA and protein involved in a wide range of cellular processes, including protein synthesis) in regulating the activation of T-cells, a type of white blood cell.
"This work should provide significant new insights into the structure of ribonucleoprotein complexes in general," said Williamson. "In addition, we hope to gain new insights into how these complexes are involved in posttranscriptional gene regulation."
"Understanding how T cells draw from all the information embedded in the human genome to determine how to respond to an immune challenge like a virus, tumor cell, or transplant is an opportunity to study the mechanisms of health and disease," added Salomon, "and to do this at the level of protein structures in this new collaboration with the JCSG is a remarkable opportunity to advance translation biology and medicine."
The scientists will use genomic, biochemical, and functional research in combination with structural studies to forge new inroads in the field.
Membrane Protein Structures
The new grants also support nine centers - two of which are based at The Scripps Research Institute - for determining membrane protein structures. Membrane proteins, which are embedded in the membranes of our cells, are important because they enable our nerves, muscles, and even hormones to do their jobs. Currently, however, scientists can't easily visualize their three-dimensional shapes to understand how these proteins function.
The Scripps Research Institute center led by Stevens, Cherezov, Kuhn, Rosen, and WГјthrich will focus on a special class of human membrane proteins called G protein-coupled receptors (GPCRs), signaling molecules that span the membranes of cells, "sensing" chemical messages outside the cells and converting them into action within the cell. GPCRs are the largest family of proteins in the human genome.
"Our fundamental understanding of GPCR molecular recognition and signaling is still in the early stages," said Stevens. "Through the creation of the GPCR Network center, we will work directly with the GPCR community on improving our basic understanding of receptor structure and function using a variety of biophysical techniques including NMR, HDX, and X-ray crystallography, as well as computational and chemical screening techniques. Only a few GPCR structures in their inactive state have been solved to date and the basic understanding of this key membrane protein class will change drastically in the next five years with the NIH funding."
In a separate group, Chang, Rees, and Stowell will focus on a class of proteins called transporters - a type of large protein that resides in the cell membrane and moves other molecules in and out. Transporters are vital to the biology of all cells and a variety of diseases occur when these processes are perturbed or disrupted, as in several genetic disorders. In addition, cancer cells resist chemotherapy by using these transporters, and bacterial cells use them to resist antibiotics.
"We actually have very good drugs to fight cancer and to kill bacteria," said Chang. "[But] they can't always get into the cells to work."
This new center, dubbed TransportPDB, aims to develop a comprehensive and efficient approach for pursuing the high-resolution x-ray crystal structures of several transporters that PSI scientists have selected as important in biomedicine.
Source:
Mika Ono
Scripps Research Institute
"The grants are an acknowledgement of The Scripps Research Institute's leadership in the field of structural studies," said Scripps Research President Richard A. Lerner, M.D. "We're looking forward to many more important advances from our scientists thanks to this latest round of support from the NIH."
The four Scripps Research grants are part of the NIH Protein Structure Initiative (PSI), an effort that started in 2000 with the main goal of developing highly efficient methods for solving the structures of many different proteins. The new grants mark the beginning of the effort's third phase, called "PSI:Biology." A key aim of this phase is to apply the high-throughput methods developed during the initiative's first decade to challenging biological problems and systems.
"These awards to Scripps Research represent the key elements of the Protein Structure Initiative - from generating structures and new structure determination methods for particularly challenging proteins to harnessing the power of high-throughput to address important biological problems," said Ward Smith, Ph.D., director of the PSI. "Together, these approaches can significantly advance our understanding of the role proteins play in health and disease."
The Scripps Research grants are:
$37.6 million to a consortium led by Ian A. Wilson, D.Phil., Hansen Professor of Structural Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research.
$5.8 million to a group led by Jamie Williamson, Ph.D., professor, dean of the graduate school, and member of the Skaggs Institute, and Daniel R. Salomon, M.D., associate professor and Medical Director of the Scripps Center for Organ and Cell Transplantation
$16.8 million to a center led by Raymond Stevens, Ph.D., professor in the Departments of Molecular Biology and Chemistry, together with Scripps Research investigators Assistant Professor Vadim Cherezov, Associate Professor Peter Kuhn, Professor Hugh Rosen, and Professor Kurt WГјthrich
$5 million to the Scripps Research portion of a collaboration led by Geoffrey Chang, Ph.D., associate professor and member of the Skaggs Institute, in conjunction with Doug Rees, Howard Hughes Medical Institute investigator and Professor at the California Institute of Technology, and Michael Stowell, associate professor at the University of Colorado. The total for this grant is $11.5 million.
Large-Scale Structure Determination
Building on a decade of success and the solution of more than 1,000 structures, Wilson will continue to lead one of four, long-standing, large-scale PSI centers.
The consortium - called the Joint Center for Structural Genomics (JCSG) and comprising scientists at the University of California, San Diego; Genomics Institute of the Novartis Research Foundation (GNF); Sanford-Burnham Medical Research Institute; and Stanford Synchrotron Radiation Lightsource (SSRL), Stanford University - will continue to operate its pipeline for high-throughput structure determination. Structures that the group plans to tackle over the next five years include challenging targets, such as eukaryotic proteins, as well as protein-protein, protein-RNA, protein-DNA, and other complexes.
One theme of the center's research will be the human "microbiome," the totality of microbes in a defined environment, such as the human digestive tract.
"Interactions of bacteria with the human body are profound and have a significant impact on maintenance of general human health," said Wilson. "In addition, they are associated with obesity, inflammatory diseases, diabetes, and certain cancers, to name but a few disorders."
The center will focus on solving these structures by continuing to hone their highly efficient methods and by conducting collaborative research, including with scientists outside the PSI network.
Biological Problems
The JCSG and other large-scale centers will partner with eight groups of biologists, including one based at Scripps Research, that require the determination of many protein and protein-RNA structures to understand biological processes or a molecule's function.
The Scripps Research center, led by Williamson and Salomon, will focus on better understanding the workings of part of our immune system, which protects us against disease by fending off pathogens such as bacteria, viruses, and tumor cells. The immune system is also a critical determinant of the success or failure of kidney, heart, liver, and bone marrow cell transplants. In particular, the scientists aim to better understand the role of ribonucleoproteins (complexes of RNA and protein involved in a wide range of cellular processes, including protein synthesis) in regulating the activation of T-cells, a type of white blood cell.
"This work should provide significant new insights into the structure of ribonucleoprotein complexes in general," said Williamson. "In addition, we hope to gain new insights into how these complexes are involved in posttranscriptional gene regulation."
"Understanding how T cells draw from all the information embedded in the human genome to determine how to respond to an immune challenge like a virus, tumor cell, or transplant is an opportunity to study the mechanisms of health and disease," added Salomon, "and to do this at the level of protein structures in this new collaboration with the JCSG is a remarkable opportunity to advance translation biology and medicine."
The scientists will use genomic, biochemical, and functional research in combination with structural studies to forge new inroads in the field.
Membrane Protein Structures
The new grants also support nine centers - two of which are based at The Scripps Research Institute - for determining membrane protein structures. Membrane proteins, which are embedded in the membranes of our cells, are important because they enable our nerves, muscles, and even hormones to do their jobs. Currently, however, scientists can't easily visualize their three-dimensional shapes to understand how these proteins function.
The Scripps Research Institute center led by Stevens, Cherezov, Kuhn, Rosen, and WГјthrich will focus on a special class of human membrane proteins called G protein-coupled receptors (GPCRs), signaling molecules that span the membranes of cells, "sensing" chemical messages outside the cells and converting them into action within the cell. GPCRs are the largest family of proteins in the human genome.
"Our fundamental understanding of GPCR molecular recognition and signaling is still in the early stages," said Stevens. "Through the creation of the GPCR Network center, we will work directly with the GPCR community on improving our basic understanding of receptor structure and function using a variety of biophysical techniques including NMR, HDX, and X-ray crystallography, as well as computational and chemical screening techniques. Only a few GPCR structures in their inactive state have been solved to date and the basic understanding of this key membrane protein class will change drastically in the next five years with the NIH funding."
In a separate group, Chang, Rees, and Stowell will focus on a class of proteins called transporters - a type of large protein that resides in the cell membrane and moves other molecules in and out. Transporters are vital to the biology of all cells and a variety of diseases occur when these processes are perturbed or disrupted, as in several genetic disorders. In addition, cancer cells resist chemotherapy by using these transporters, and bacterial cells use them to resist antibiotics.
"We actually have very good drugs to fight cancer and to kill bacteria," said Chang. "[But] they can't always get into the cells to work."
This new center, dubbed TransportPDB, aims to develop a comprehensive and efficient approach for pursuing the high-resolution x-ray crystal structures of several transporters that PSI scientists have selected as important in biomedicine.
Source:
Mika Ono
Scripps Research Institute
четверг, 16 июня 2011 г.
A Tricky Tumor Virus: Epstein-Barr Virus Reprograms The Biological Properties Of A Signal Protein Of Its Host Cells
Viruses use many tricks to gain control over their host cells and to reprogram them to their own advantage. Dr. Arnd Kieser and his colleagues of the Department of Gene Vectors of the Helmholtz Zentrum MГјnchen, Germany, were able to show in a recent publication in PloS Biology by which mechanism Epstein-Barr virus exploits a signal protein of its host cell, which normally mediates programmed cell death (apoptosis), in order to convert the cell into a cancer cell.
Epstein-Barr virus (EBV) is a human-pathogenic virus which belongs to the herpes virus family. Almost every adult carries EBV inside. With an infestation rate of more than 90 %, EBV is one of the most successful human viruses. Its viral genome consists of double-stranded DNA, and it is one of the few known viruses which cause cancer in humans under certain circumstances. EBV-associated cancers include lymphomas (cancer of the lymph nodes), nasopharyngeal carcinoma and gastric cancer.
A protein encoded by the virus, the latent membrane protein 1 (LMP1), is required for the uncontrolled proliferation of EBV-infected cells and, thus, the formation of cancer. Arnd Kieser and his team are studying the molecular mode of action of this EBV protein. LMP1 is a membrane-bound oncoprotein that binds certain signal molecules of its host cell and thereby critically contributes to the oncogenic transformation of the cells. One of these signal proteins is the factor TRADD. TRADD stands for TNF-receptor 1-associated death domain protein. The scientists used TRADD knockout cell lines which they had established by removing the TRADD gene from the genome of human B-cells in order to demonstrate that TRADD is an essential factor for LMP1 function. They found that in the absence of TRADD, LMP1 can no longer activate a cellular communication (also called: signal transduction) pathway which is crucial for cell transformation. However, TRADD's normal function within the cell includes the induction of programmed cell death which would be fatal for the virus. In fact, the scientists made the surprising observation that TRADD can no longer induce apoptosis if it is activated by the viral protein LMP1.
How does Epstein-Barr virus manage to switch off the apoptosis function of TRADD? Kieser and his colleagues discovered that the LMP1 protein possesses a unique TRADD binding domain which dictates an unusual TRADD interaction and prevents TRADD from transmitting cell death signals. Thus, LMP1 masks the apoptotic activity of TRADD. This viral TRADD-binding domain consists of the 16 carboxyterminal amino acids of the LMP1 protein and can be transplanted to cellular receptor proteins where it shows the same effects.
Hence, Epstein-Barr virus has found a unique molecular way to extinguish an undesired property of a cellular protein in order to adapt this protein to its own needs. This finding might also be the basis for a new therapeutic approach. Arnd Kieser explains: "Since the specific structure of the LMP1-TRADD interaction is most likely restricted to EBV-infected cells, it might serve as a target structure to develop specific inhibitors which interrupt the transforming signal cascade of the LMP1 oncogene."
HELMHOLTZ ZENTRUM MUENCHEN - GERMAN RESEARCH CENTER FOR ENVIRONMENTAL HEALTH
Ingolstaedter LandstraГџe 1
D-85764 Neuherberg
gsf
Epstein-Barr virus (EBV) is a human-pathogenic virus which belongs to the herpes virus family. Almost every adult carries EBV inside. With an infestation rate of more than 90 %, EBV is one of the most successful human viruses. Its viral genome consists of double-stranded DNA, and it is one of the few known viruses which cause cancer in humans under certain circumstances. EBV-associated cancers include lymphomas (cancer of the lymph nodes), nasopharyngeal carcinoma and gastric cancer.
A protein encoded by the virus, the latent membrane protein 1 (LMP1), is required for the uncontrolled proliferation of EBV-infected cells and, thus, the formation of cancer. Arnd Kieser and his team are studying the molecular mode of action of this EBV protein. LMP1 is a membrane-bound oncoprotein that binds certain signal molecules of its host cell and thereby critically contributes to the oncogenic transformation of the cells. One of these signal proteins is the factor TRADD. TRADD stands for TNF-receptor 1-associated death domain protein. The scientists used TRADD knockout cell lines which they had established by removing the TRADD gene from the genome of human B-cells in order to demonstrate that TRADD is an essential factor for LMP1 function. They found that in the absence of TRADD, LMP1 can no longer activate a cellular communication (also called: signal transduction) pathway which is crucial for cell transformation. However, TRADD's normal function within the cell includes the induction of programmed cell death which would be fatal for the virus. In fact, the scientists made the surprising observation that TRADD can no longer induce apoptosis if it is activated by the viral protein LMP1.
How does Epstein-Barr virus manage to switch off the apoptosis function of TRADD? Kieser and his colleagues discovered that the LMP1 protein possesses a unique TRADD binding domain which dictates an unusual TRADD interaction and prevents TRADD from transmitting cell death signals. Thus, LMP1 masks the apoptotic activity of TRADD. This viral TRADD-binding domain consists of the 16 carboxyterminal amino acids of the LMP1 protein and can be transplanted to cellular receptor proteins where it shows the same effects.
Hence, Epstein-Barr virus has found a unique molecular way to extinguish an undesired property of a cellular protein in order to adapt this protein to its own needs. This finding might also be the basis for a new therapeutic approach. Arnd Kieser explains: "Since the specific structure of the LMP1-TRADD interaction is most likely restricted to EBV-infected cells, it might serve as a target structure to develop specific inhibitors which interrupt the transforming signal cascade of the LMP1 oncogene."
HELMHOLTZ ZENTRUM MUENCHEN - GERMAN RESEARCH CENTER FOR ENVIRONMENTAL HEALTH
Ingolstaedter LandstraГџe 1
D-85764 Neuherberg
gsf
среда, 15 июня 2011 г.
Arteriocyte Announces The Launch Of NANEX™ Stem Cell Expansion System At The Upcoming American Society Of Cell Biology Meeting
Arteriocyte, Inc., a leading clinical stage biotechnology company with offices in Cleveland, Ohio, and Hopkinton, Massachusetts, that develops proprietary stem cell and tissue engineering based therapies announced the launch of its first commercially available Stem Cell Expansion System for research use. The NANEX™ Hematopoietic stem cell expansion kit will be featured at the 50th Annual Meeting of the American Society of Cell Biology in Philadelphia December 11th-15th. The NANEX™ platform consists of a biofunctional nanofiber-based 3D scaffold designed to mimic the microenvironmental cues from the bone marrow niche, permitting rapid ex vivo proliferation of hematopoietic stem cells with minimal differentiation. The NANEX™ Stem Cell Expansion Kit will enable researchers to more cost effectively expand hematopoietic stem cells (HSCs) for use in studying mechanisms of hematopoiesis and angiogenesis, investigating disease mechanisms for cardiovascular and blood diseases, and for the pre-clinical development of cell-based therapies using cultured HSCs.
Arteriocyte's NANEX™ Hematopoietic Stem Cell Expansion Kit represents the company's first commercial research product offering based on propriety stem cell expansion technology developed by Dr. Hai-Quan Mao of the Johns Hopkins University, supported by funding from the National Institutes of Health and National Science Foundation, and under exclusive license to Arteriocyte.
"The introduction of our NANEX™ stem cell culturing plates into the research community represents another important step in Arteriocyte's continued commitment to advancing the understanding of the mechanisms of stem cell growth and differentiation with the ultimate goal of enabling cell based clinical therapies," said Don Brown, Chief Executive Officer, Arteriocyte, Inc. "The NANEX™ cell expansion kit is one of the first complete, easy to use kits that will enable cell-biology and cell-based research teams to rapidly and more cost effectively expand HSC's for use in their research."
Arteriocyte has multiple pre-clinical research programs centered on the NANEX technology targeting clinical applications including the treatment of ischemia, cancers of the blood system and rapid high volume ex vivo red blood cell production. Arteriocyte's clinical research collaborations include many of the world's leading academic and clinical research institutions. With support from the Ohio Third Frontier Research Commercialization Program, the company was able to establish and scale up NANEX™ manufacturing systems in its new Cleveland-based Research and Development Center.
The NANEX™ Hematopoietic Stem Cell Expansion Kit, including cultureware, expansion medium and growth supplements will be available for order following its formal launch at the American Society of Cell Biology 50th Annual Meeting at the Pennsylvania Convention Center (Philadelphia, PA). Attendees can learn more about the product at Booth 1335 from December 12th to 14th.
Source: Arteriocyte, Inc.
Arteriocyte's NANEX™ Hematopoietic Stem Cell Expansion Kit represents the company's first commercial research product offering based on propriety stem cell expansion technology developed by Dr. Hai-Quan Mao of the Johns Hopkins University, supported by funding from the National Institutes of Health and National Science Foundation, and under exclusive license to Arteriocyte.
"The introduction of our NANEX™ stem cell culturing plates into the research community represents another important step in Arteriocyte's continued commitment to advancing the understanding of the mechanisms of stem cell growth and differentiation with the ultimate goal of enabling cell based clinical therapies," said Don Brown, Chief Executive Officer, Arteriocyte, Inc. "The NANEX™ cell expansion kit is one of the first complete, easy to use kits that will enable cell-biology and cell-based research teams to rapidly and more cost effectively expand HSC's for use in their research."
Arteriocyte has multiple pre-clinical research programs centered on the NANEX technology targeting clinical applications including the treatment of ischemia, cancers of the blood system and rapid high volume ex vivo red blood cell production. Arteriocyte's clinical research collaborations include many of the world's leading academic and clinical research institutions. With support from the Ohio Third Frontier Research Commercialization Program, the company was able to establish and scale up NANEX™ manufacturing systems in its new Cleveland-based Research and Development Center.
The NANEX™ Hematopoietic Stem Cell Expansion Kit, including cultureware, expansion medium and growth supplements will be available for order following its formal launch at the American Society of Cell Biology 50th Annual Meeting at the Pennsylvania Convention Center (Philadelphia, PA). Attendees can learn more about the product at Booth 1335 from December 12th to 14th.
Source: Arteriocyte, Inc.
вторник, 14 июня 2011 г.
NIH Director Zerhouni Assumes Greater Budget Authority Over Research Under New Law
A "little-noticed" bill signed by President Bush this month, which grants NIH Director Elias Zerhouni greater budget authority over the institute's research, has prompted concern among patient advocacy groups who fear their research will be compromised, the Wall Street Journal reports. Under the law, Zerhouni and future NIH directors will be able to organize a "common fund" that eventually would pool about 5% of NIH's money to fund research projects that span traditional biomedical fields. The institute's budget previously was managed by the 27 separate institutes and centers within NIH, all of which have ties to patient advocacy groups representing a variety of diseases. Such groups are concerned that the common fund will increase "at the expense of their own research, carving money out of their funds," the Journal reports. Zerhouni says new funding will promote trans-disciplinary research, and obesity and nanotechnology research will be high priorities. According to the Journal, a successful pilot project for the common fund, called the NIH Roadmap, "helped bolster the case for more centralized pooling of funds." The NIH Roadmap and other trans-NIH programs currently account for 1% of NIH's budget. Zerhouni acknowledged that it would take "multiple years" for the fund to increase to 5% of the overall budget. Once it does, Zerhouni must report to Congress, which has earmarked $483 million for the common fund in its proposed fiscal year 2007 budget resolution. Under the law, the common fund eventually could grow larger than 5% of the budget. According to Zerhouni, funding will be awarded by a peer-review process and an NIH special council will advise on spending. Rep. Joe Barton (R-Texas), at times a critic of NIH, said the new legislation would "strengthen the research efforts of the NIH and will provide the foundation for future scientific and medical advancement" (Wysocki, Wall Street Journal, 1/31).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
понедельник, 13 июня 2011 г.
Unraveling The Natural History Of The Lion Using Host And Virus Population Genomics
The lion (Panthera leo) is one of the world's most charismatic carnivores. In an article published November 7 in the open-access journal PLoS
Genetics, an international team of researchers provides insights into the genetic structure and history of lion populations. Their work refutes the
hypothesis that African lions consist of a single, randomly breeding (panmictic) population. It also indicates the importance of preserving
populations in decline as opposed to prioritizing larger-scale conservation efforts.
Understanding the broader aspects of the evolutionary history of the lion has been hindered by a lack of comprehensive sampling and appropriately
informative genetic markers. Nevertheless, the unique social ecology of lions and the well-documented infectious diseases they have experienced,
including lion-specific feline immunodeficiency virus (FIVPle), provides the opportunity to study lion evolutionary history using both host and virus
genetic information.
In total, a comprehensive sample of 357 individuals from most of the major lion populations in Africa and Asia were studied. The authors compared the
large multigenic dataset from lions with patterns of genetic variation of FIVPle to characterize the genomic legacy of lion populations. The research
reveals evidence of unsuspected genetic diversity even in the well-studied lion population of the Serengeti ecosystem, which consists of recently
admixed animals derived from three distinct genetic groups.
"The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics."
Antunes A, Troyer JL, Roelke ME, Pecon-Slattery J, Packer C, et al. (2008)
PLoS Genet 4(11): e1000251. doi:10.1371/journal.pgen.1000251
Click here to view article online
About PLoS Genetics
PLoS Genetics reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing
outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely
available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is
retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
PLoS Genetics
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource. For more information, visit plos.
Public Library of Science
Genetics, an international team of researchers provides insights into the genetic structure and history of lion populations. Their work refutes the
hypothesis that African lions consist of a single, randomly breeding (panmictic) population. It also indicates the importance of preserving
populations in decline as opposed to prioritizing larger-scale conservation efforts.
Understanding the broader aspects of the evolutionary history of the lion has been hindered by a lack of comprehensive sampling and appropriately
informative genetic markers. Nevertheless, the unique social ecology of lions and the well-documented infectious diseases they have experienced,
including lion-specific feline immunodeficiency virus (FIVPle), provides the opportunity to study lion evolutionary history using both host and virus
genetic information.
In total, a comprehensive sample of 357 individuals from most of the major lion populations in Africa and Asia were studied. The authors compared the
large multigenic dataset from lions with patterns of genetic variation of FIVPle to characterize the genomic legacy of lion populations. The research
reveals evidence of unsuspected genetic diversity even in the well-studied lion population of the Serengeti ecosystem, which consists of recently
admixed animals derived from three distinct genetic groups.
"The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics."
Antunes A, Troyer JL, Roelke ME, Pecon-Slattery J, Packer C, et al. (2008)
PLoS Genet 4(11): e1000251. doi:10.1371/journal.pgen.1000251
Click here to view article online
About PLoS Genetics
PLoS Genetics reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing
outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely
available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is
retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
PLoS Genetics
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource. For more information, visit plos.
Public Library of Science
воскресенье, 12 июня 2011 г.
Breakthrough In The Design Of New Drugs - New Way Of Recognising DNA
Scientists led by Mike Hannon at the University of Birmingham and Miquel Coll at the Spanish Research Council in Barcelona have discovered a new way that drugs can attach themselves to DNA, which is a crucial step forward for researchers who are developing drugs to combat cancer and other diseases.
DNA contains the information which encodes life itself; its double-helical structure was recognised 50 years ago. Scientists soon started designing drugs to target DNA and used them to treat diseases such as cancer, viral infections and sleeping sickness. In the 1960s, scientists discovered three different classes of clinical drug, each of which recognised DNA in a different way. Subsequent drugs have used only these three ways to recognise the DNA. Now the Birmingham and Barcelona teams have found a fourth which is completely different and opens up entirely new possibilities for drug design.
The scientists have developed a synthetic drug agent that targets and binds to the centre of a 3-way junction in the DNA. These 3-way junction structures are formed where three double-helical regions join together. They are particularly exciting as they have been found to be present in diseases, such as some Huntington's disease and myotonic dystrophy, in viruses and whenever DNA replicates itself, for example, during cancer growth.
First of all, the Birmingham team created a nanosize synthetic drug in the shape of a twisted cylinder. Together with researchers in the UK, Spain and Norway they showed that is had unprecedented effects on DNA. Now molecular level pictures taken by the Barcelona team have shown that it binds itself in a new way to the DNA, by fixing itself to the centre of a DNA junction, which had three strands. It is all held together because the cylinder is positively charged and the DNA is negatively charged. In addition the drug is a perfect fit in the heart of the junction: a round peg in a round hole.
DNA is the genetic code in humans which carries all the information needed by our bodies in order to function properly. It is divided into units of genes. When a disease is present, genes are either working too hard or not enough, so to combat this, scientists are looking for ways to target those genes to turn them off or on or to make them work slower or faster. A number of current anti-cancer drugs target disease at DNA level, but they are not specific in their approach and this means that they can cause unpleasant side effects. Moreover some of these drugs suffer from developed resistance as the body learns how to deal with drugs that act in a particular way. By creating drugs which act in completely different ways this acquired resistance could be overcome.
Professor Mike Hannon, from the University of Birmingham's School of Chemistry, says, 'This is a significant step in drug design for DNA recognition and it is an absolutely crucial step forward for medical science researchers worldwide who are working on new drug targets for cancer and other diseases. This discovery will revolutionise the way that we think about how to design molecules to interact with DNA. It will send chemical drug research off on a new tangent. By targeting specific structures in the DNA scientists may finally start to achieve control over the way our genetic information is processed and apply that to fight disease'
Professor Miquel Coll's team from the Spanish Research Council in Barcelona was able to obtain the molecular level picture of how the drug interacts with the DNA using a technique called X-ray crystallography at the European Synchrotron facility at Grenoble in France. Professor Miquel Coll says, 'In 1999 we solved the structure of the four-way DNA junction -also called Holliday junction- which is how two DNA helices can 'recombine' (swop genetic information) and which is important in producing genetic diversity in humans and other organisms. But that junction was rather compact, without cavities or holes that could be used for drug binding. Now we have discovered that three-way DNA junctions are much more suitable for drug design: they leave a central cavity where a drug can fit perfectly and this opens a door for the design of new and quite unprecedented anti-DNA agents.'
1. DNA holds the human genetic code. To express this information, DNA copies itself into RNA, which holds exactly the same information. The RNA molecules create proteins which have a specific job to carry out, for example, they can be enzymes. To combat disease drug targets can be developed to work with DNA, RNA or proteins. For scientists, it is easier to target DNA, as only one molecule of the drug target is needed.
2. This work is part of a trans-European collaborative effort led by Prof. Mike Hannon, leader of the Birmingham research team and based around the agents developed by that team. The consortium which is funded by the European Commission Framework research programme involves research teams at: CSIC Barcelona, Spain; Chalmers University, Gothenburg, Sweden; Bergen University, Norway, University of Barcelona, Spain; Institute of Biophysics, Brno, Czech Republic. The work is focused on designing and studying the DNA binding of synthetic agents that are similar in size to the agents biology uses to recognise DNA. The team leader at CSIC Barcelona is structural biologist Prof. Miquel Coll.
3. The three previous modes of DNA recognition used by drugs are:
a. Slotting in between the DNA base pairs at the heart of the DNA (usually described by scientists as "intercalation"). This is like a sandwich with the DNA bases being the bread and the drug being the filling. An early example of such a drug used to treat cancer was doxorubicin (trade name 'Adriamycin' or 'Rubex'). This drug, launched in the 1960s, gave much impetus to the field and has been followed by a number of varients. This 'intercalation' binding mode was recognized in the early 1960s. Doxorubicin is classified by clinicians as an "anthracycline antiobiotic."
b. Binding in the grooves which are formed as the DNA strands wrap about each other to form the spiral (double-helical) structure. Examples of such drugs include berenil and stilbamidine, pentamidine. This mode of binding had been recognized in the late 1960s; some of the drugs were in the clinic by this time.
c. Forming direct bonds to the DNA bases that hold the genetic information and causing distortions to DNA structure. This mode of action is used by the platinum drugs that are among the most widely used anti-cancer agents in clinic today. The original platinum drug cis-platin (marketed as 'platinol') was discovered in the mid 1960s when its mode of DNA-binding was first established. It was introduced into the clinic in the 1970s. Three further platinum drugs (carboplatin - trade name 'Paraplatin', nedaplatin and most recently oxaliplatin - trade name Eloxatin) are also in clinical use. Clinicians refer to this general group of chemotherapy drugs as alkylating agents.
4. The journal Angewandte Chemie is the highest impact, primary-research Chemistry journal in the world. It has judged this work so important that it has not only assigned the paper VIP status (Very Important Paper), but also elected to feature the work on its front cover and has commissioned a 'Highlight article' (from a leading player in the field of DNA recognition and metal-based drugs: Professor B. Lippert of the University of Dortmund) to be positioned at the start of the journal issue to place the work in context and underline its importance.
Peer reviewed publication and references
Angewandte Chemie
UNIVERSITY OF BIRMINGHAM
Edgbaston
Birmingham
B15 2TT
UK
The University was founded in 1900 by the citizens of Birmingham who wanted their own university to train and educate the people who would create and manage the burgeoning businesses and industries of the midlands.
bham.ac.uk
View drug information on Eloxatin.
DNA contains the information which encodes life itself; its double-helical structure was recognised 50 years ago. Scientists soon started designing drugs to target DNA and used them to treat diseases such as cancer, viral infections and sleeping sickness. In the 1960s, scientists discovered three different classes of clinical drug, each of which recognised DNA in a different way. Subsequent drugs have used only these three ways to recognise the DNA. Now the Birmingham and Barcelona teams have found a fourth which is completely different and opens up entirely new possibilities for drug design.
The scientists have developed a synthetic drug agent that targets and binds to the centre of a 3-way junction in the DNA. These 3-way junction structures are formed where three double-helical regions join together. They are particularly exciting as they have been found to be present in diseases, such as some Huntington's disease and myotonic dystrophy, in viruses and whenever DNA replicates itself, for example, during cancer growth.
First of all, the Birmingham team created a nanosize synthetic drug in the shape of a twisted cylinder. Together with researchers in the UK, Spain and Norway they showed that is had unprecedented effects on DNA. Now molecular level pictures taken by the Barcelona team have shown that it binds itself in a new way to the DNA, by fixing itself to the centre of a DNA junction, which had three strands. It is all held together because the cylinder is positively charged and the DNA is negatively charged. In addition the drug is a perfect fit in the heart of the junction: a round peg in a round hole.
DNA is the genetic code in humans which carries all the information needed by our bodies in order to function properly. It is divided into units of genes. When a disease is present, genes are either working too hard or not enough, so to combat this, scientists are looking for ways to target those genes to turn them off or on or to make them work slower or faster. A number of current anti-cancer drugs target disease at DNA level, but they are not specific in their approach and this means that they can cause unpleasant side effects. Moreover some of these drugs suffer from developed resistance as the body learns how to deal with drugs that act in a particular way. By creating drugs which act in completely different ways this acquired resistance could be overcome.
Professor Mike Hannon, from the University of Birmingham's School of Chemistry, says, 'This is a significant step in drug design for DNA recognition and it is an absolutely crucial step forward for medical science researchers worldwide who are working on new drug targets for cancer and other diseases. This discovery will revolutionise the way that we think about how to design molecules to interact with DNA. It will send chemical drug research off on a new tangent. By targeting specific structures in the DNA scientists may finally start to achieve control over the way our genetic information is processed and apply that to fight disease'
Professor Miquel Coll's team from the Spanish Research Council in Barcelona was able to obtain the molecular level picture of how the drug interacts with the DNA using a technique called X-ray crystallography at the European Synchrotron facility at Grenoble in France. Professor Miquel Coll says, 'In 1999 we solved the structure of the four-way DNA junction -also called Holliday junction- which is how two DNA helices can 'recombine' (swop genetic information) and which is important in producing genetic diversity in humans and other organisms. But that junction was rather compact, without cavities or holes that could be used for drug binding. Now we have discovered that three-way DNA junctions are much more suitable for drug design: they leave a central cavity where a drug can fit perfectly and this opens a door for the design of new and quite unprecedented anti-DNA agents.'
1. DNA holds the human genetic code. To express this information, DNA copies itself into RNA, which holds exactly the same information. The RNA molecules create proteins which have a specific job to carry out, for example, they can be enzymes. To combat disease drug targets can be developed to work with DNA, RNA or proteins. For scientists, it is easier to target DNA, as only one molecule of the drug target is needed.
2. This work is part of a trans-European collaborative effort led by Prof. Mike Hannon, leader of the Birmingham research team and based around the agents developed by that team. The consortium which is funded by the European Commission Framework research programme involves research teams at: CSIC Barcelona, Spain; Chalmers University, Gothenburg, Sweden; Bergen University, Norway, University of Barcelona, Spain; Institute of Biophysics, Brno, Czech Republic. The work is focused on designing and studying the DNA binding of synthetic agents that are similar in size to the agents biology uses to recognise DNA. The team leader at CSIC Barcelona is structural biologist Prof. Miquel Coll.
3. The three previous modes of DNA recognition used by drugs are:
a. Slotting in between the DNA base pairs at the heart of the DNA (usually described by scientists as "intercalation"). This is like a sandwich with the DNA bases being the bread and the drug being the filling. An early example of such a drug used to treat cancer was doxorubicin (trade name 'Adriamycin' or 'Rubex'). This drug, launched in the 1960s, gave much impetus to the field and has been followed by a number of varients. This 'intercalation' binding mode was recognized in the early 1960s. Doxorubicin is classified by clinicians as an "anthracycline antiobiotic."
b. Binding in the grooves which are formed as the DNA strands wrap about each other to form the spiral (double-helical) structure. Examples of such drugs include berenil and stilbamidine, pentamidine. This mode of binding had been recognized in the late 1960s; some of the drugs were in the clinic by this time.
c. Forming direct bonds to the DNA bases that hold the genetic information and causing distortions to DNA structure. This mode of action is used by the platinum drugs that are among the most widely used anti-cancer agents in clinic today. The original platinum drug cis-platin (marketed as 'platinol') was discovered in the mid 1960s when its mode of DNA-binding was first established. It was introduced into the clinic in the 1970s. Three further platinum drugs (carboplatin - trade name 'Paraplatin', nedaplatin and most recently oxaliplatin - trade name Eloxatin) are also in clinical use. Clinicians refer to this general group of chemotherapy drugs as alkylating agents.
4. The journal Angewandte Chemie is the highest impact, primary-research Chemistry journal in the world. It has judged this work so important that it has not only assigned the paper VIP status (Very Important Paper), but also elected to feature the work on its front cover and has commissioned a 'Highlight article' (from a leading player in the field of DNA recognition and metal-based drugs: Professor B. Lippert of the University of Dortmund) to be positioned at the start of the journal issue to place the work in context and underline its importance.
Peer reviewed publication and references
Angewandte Chemie
UNIVERSITY OF BIRMINGHAM
Edgbaston
Birmingham
B15 2TT
UK
The University was founded in 1900 by the citizens of Birmingham who wanted their own university to train and educate the people who would create and manage the burgeoning businesses and industries of the midlands.
bham.ac.uk
View drug information on Eloxatin.
суббота, 11 июня 2011 г.
Network-based Diffusion Analysis: A New Method For Detecting Social Learning
Social learning is a key mechanism by which many animals acquire adaptive behaviours from other group members, which eventually can lead to the emergence of traditions, with human culture being the most complex example.
However, our ability to investigate social learning dynamics in animals is limited by the methods that are currently available. We address this challenge with an innovative, new approach that analyzes the spread of traits through animal groups.
We tested our method with artificially generated learning data. Our results demonstrate the superior power of our method in comparison to another widely-used method.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of the journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
However, our ability to investigate social learning dynamics in animals is limited by the methods that are currently available. We address this challenge with an innovative, new approach that analyzes the spread of traits through animal groups.
We tested our method with artificially generated learning data. Our results demonstrate the superior power of our method in comparison to another widely-used method.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of the journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
пятница, 10 июня 2011 г.
Differentiation Blocked In Tumor Stem Cells
A new comparison of normal stem cells and cancer stem cells reveals that the cancer stem cells are abnormally trapped at an early stage of development. The research, published by Cell Press in the January issue of Cancer Cell, significantly advances the understanding of glioma pathophysiology and provides new directions for design of therapeutic strategies that are targeted to specific types of tumors.
Tumor-initiating cells with stem like properties (TICs) are thought to be a small population of tumor cells that have many characteristics in common with normal stem cells (NSCs) in that they are self-replicating and capable of giving rise to populations of differentiated cells. Previous research has demonstrated that TICs are present in different types of brain tumors, including glioblastomas. Although the TICs share many properties with NSCs, they are known to possess genetic aberrations that support a tumorigenic phenotype.
"Thus far, there have been few, if any, reports demonstrating exactly where along the developmental pathway of tissue-specific stem cell maturation and differentiation tumor stem cells arise, and which, if any, of the intrinsic stem cell signaling pathways are perturbed in tumor stem cells remains largely unknown," explains Dr. Howard A. Fine from the National Cancer Institute in Bethesda, Maryland. To better understand the development and differentiation pathways that play a significant role in cancer stem cells, Dr. Fine and colleagues isolated TICs from primary human glioblastomas and compared them to human and mouse NSCs at various developmental stages.
The researchers found that the TICs isolated from an adult patient are more similar to early embryonic stem cells than to later embryonic or adult-derived stem cells. Specifically, the TICs appear to be stuck at this early developmental stage, at least in part, due to epigenetic repression of bone morphogenic protein receptor 1B (BMPR1B) expression mediated through a polycomb repressive complex. BMPs are known to mediate proliferation, differentiation and apoptosis in NSCs, depending on the stage of cell development and the local environment. Importantly, forced expression of the silenced BMPR1B restored normal differentiation capacity to the isolated TICs, halting further cell division and inducing terminal differentiation.
"Our research provides an example of a temporally deregulated and aberrantly fixed normal stem cell developmental block to differentiation contributing to the pathogenesis of a human tumor. Not only will such insights pave the way for a more thorough understanding of tumor stem cell biology, but they also identify BMPR1B as a promising molecular target and open the potential for targeted therapeutic approaches for agents that can induce terminal differentiation of tumor stem cells," offers Dr. Fine.
The researchers include Jeongwu Lee, Myung Jin Son, Kevin Woolard, Nicholas M. Donin, Aiguo Li, Chui H. Cheng, Svetlana Kotliarova, Yuri Kotliarov, Jennifer Walling, Susie Ahn, Misuk Kim, Mariam Totonchy, Thomas Cusack, Chibawanye Ene, Hilary Ma, Qin Su, Jean Claude Zenklusen, Wei Zhang, Dragan Maric, and Howard A. Fine of the Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurological Diseases and Stroke, National Institutes of Health in Bethesda.
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
Lee et al.: "Epigenetic-Mediated Dysfunction of the Bone Morphogenetic Protein Pathway Inhibits Differentiation of Glioblastoma-Initiating Cells." Publishing in Cancer Cell 13, 69-80, January 2008. DOI 10.1016/j.ccr.2007.12.005. cancercell/
Source: Cathleen Genova
Cell Press
Tumor-initiating cells with stem like properties (TICs) are thought to be a small population of tumor cells that have many characteristics in common with normal stem cells (NSCs) in that they are self-replicating and capable of giving rise to populations of differentiated cells. Previous research has demonstrated that TICs are present in different types of brain tumors, including glioblastomas. Although the TICs share many properties with NSCs, they are known to possess genetic aberrations that support a tumorigenic phenotype.
"Thus far, there have been few, if any, reports demonstrating exactly where along the developmental pathway of tissue-specific stem cell maturation and differentiation tumor stem cells arise, and which, if any, of the intrinsic stem cell signaling pathways are perturbed in tumor stem cells remains largely unknown," explains Dr. Howard A. Fine from the National Cancer Institute in Bethesda, Maryland. To better understand the development and differentiation pathways that play a significant role in cancer stem cells, Dr. Fine and colleagues isolated TICs from primary human glioblastomas and compared them to human and mouse NSCs at various developmental stages.
The researchers found that the TICs isolated from an adult patient are more similar to early embryonic stem cells than to later embryonic or adult-derived stem cells. Specifically, the TICs appear to be stuck at this early developmental stage, at least in part, due to epigenetic repression of bone morphogenic protein receptor 1B (BMPR1B) expression mediated through a polycomb repressive complex. BMPs are known to mediate proliferation, differentiation and apoptosis in NSCs, depending on the stage of cell development and the local environment. Importantly, forced expression of the silenced BMPR1B restored normal differentiation capacity to the isolated TICs, halting further cell division and inducing terminal differentiation.
"Our research provides an example of a temporally deregulated and aberrantly fixed normal stem cell developmental block to differentiation contributing to the pathogenesis of a human tumor. Not only will such insights pave the way for a more thorough understanding of tumor stem cell biology, but they also identify BMPR1B as a promising molecular target and open the potential for targeted therapeutic approaches for agents that can induce terminal differentiation of tumor stem cells," offers Dr. Fine.
The researchers include Jeongwu Lee, Myung Jin Son, Kevin Woolard, Nicholas M. Donin, Aiguo Li, Chui H. Cheng, Svetlana Kotliarova, Yuri Kotliarov, Jennifer Walling, Susie Ahn, Misuk Kim, Mariam Totonchy, Thomas Cusack, Chibawanye Ene, Hilary Ma, Qin Su, Jean Claude Zenklusen, Wei Zhang, Dragan Maric, and Howard A. Fine of the Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurological Diseases and Stroke, National Institutes of Health in Bethesda.
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
Lee et al.: "Epigenetic-Mediated Dysfunction of the Bone Morphogenetic Protein Pathway Inhibits Differentiation of Glioblastoma-Initiating Cells." Publishing in Cancer Cell 13, 69-80, January 2008. DOI 10.1016/j.ccr.2007.12.005. cancercell/
Source: Cathleen Genova
Cell Press
четверг, 9 июня 2011 г.
How Does CO2 Insufflation Pressure Affect Proliferation And Improve Apoptosis?
Under 10 mmHg CO2 pressure, there were no obvious effects on MKN-45 cells' proliferation and apoptosis. At 15 mmHg CO2 insufflation pressure, cells proliferation was inhibited and apoptosis improved. It may be that CO2 gas affected the growth of gastric cancer cells.
This study was performed by a team led by Professor Pei-Wu Yu. The research article is published in the World Journal of Gastroenterology.
There is an ongoing debate on the deleterious effects of CO2 on tumor cell behavior. Some authors showed an increase in cell proliferation and tumor growth and others found beneficial effects of CO2 exposition in vitro and in animal studies.
In the view of the authors, the extracellular pH differed significantly during CO2 versus helium exposure and it decreased very sharply with the insufflated pressure. The extracellular and intracellular pH was an important regulator of cell functions, such as ATP production, cell cycle, intracellular signaling and apoptosis. It is likely that all these changes influence the favorability of tumor-cell implantation at the time of laparoscopic surgery.
The role of peritoneal microenvironment in tumor-cell growth awaits further studies and looks for the safest approach to laparoscopic oncologic surgery.
Reference: Hao YX, Zhong H, Zhang C, Zeng DZ, Shi Y, Tang B, Yu PW. Effects of simulated carbon dioxide and helium pneumoperitoneum on gastric cancer cells' proliferation and apoptosis. World J Gastroenterol 2008; 14(14): 2241-2245 wjgnet/1007-9327/14/2241.asp
Correspondence to: Pei-Wu Yu, Professor, Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Street, Shapingba district, Chongqing 400038, China.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
This study was performed by a team led by Professor Pei-Wu Yu. The research article is published in the World Journal of Gastroenterology.
There is an ongoing debate on the deleterious effects of CO2 on tumor cell behavior. Some authors showed an increase in cell proliferation and tumor growth and others found beneficial effects of CO2 exposition in vitro and in animal studies.
In the view of the authors, the extracellular pH differed significantly during CO2 versus helium exposure and it decreased very sharply with the insufflated pressure. The extracellular and intracellular pH was an important regulator of cell functions, such as ATP production, cell cycle, intracellular signaling and apoptosis. It is likely that all these changes influence the favorability of tumor-cell implantation at the time of laparoscopic surgery.
The role of peritoneal microenvironment in tumor-cell growth awaits further studies and looks for the safest approach to laparoscopic oncologic surgery.
Reference: Hao YX, Zhong H, Zhang C, Zeng DZ, Shi Y, Tang B, Yu PW. Effects of simulated carbon dioxide and helium pneumoperitoneum on gastric cancer cells' proliferation and apoptosis. World J Gastroenterol 2008; 14(14): 2241-2245 wjgnet/1007-9327/14/2241.asp
Correspondence to: Pei-Wu Yu, Professor, Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Street, Shapingba district, Chongqing 400038, China.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
среда, 8 июня 2011 г.
Battle Of The Sexes, Fruit-Fly Style
Pity the female fruit fly. Being a looker is simply not enough. To get a date, much less a proposal, you have to act like a girl, even smell like one. Otherwise, you might just have a fight on your hands.
Like most animals, fruit flies must distinguish between a potential mate and a potential competitor. When a male fruit fly suspects he's encountered a female, he'll court; when he senses the other is a male, he'll fight. What triggers these sex-specific responses?
According to new research by scientists at Harvard Medical School, the answer lies with both pheromonal profiles and behavioral patterns. The researchers investigated the effects of taste and action by manipulating a gene that governs both the sex specificity of a fruit fly's body-surface hydrocarbons, or pheromones, and the sex-linked behavioral cues that issue through the dense nerve-cell network that constitutes the fly's brain.
"These findings underscore the importance of behavioral feedback in the manifestation of aggression," says Edward Kravitz, the George Packer Berry Professor of Neurobiology at Harvard Medical School.
The research is published in the November 23 issue of PLoS Biology.
MarГa de la Paz FernГЎndez and Yick-Bun Chan, post-doctoral researchers in the Kravitz lab, discovered these links to aggression when investigating whether a male fruit fly would ever attack a female. They focused on a particular gene called transformer, which is active in females but not in males. Through blocking transformer expression in a variety of different tissues in females, the researchers could specifically alter the "femaleness" or "maleness" of the pheromones, which in turn altered the patterns of aggressive behavior encoded in the fly's brain.
When they changed pheromone profiles so that females "tasted" like males, the researchers found that males would attack them. This indicated that pheromonal cues alone could label another fly as a competitor. But the researchers were surprised to discover that males also attacked "aggressive females" - flies that still looked, smelled and tasted female but had been genetically altered to display male-like patterns of behavior.
When the researchers turned the tables by triggering the expression of transformer in males so as to feminize both the pheromonal and behavioral profiles, control males showed no aggression toward the transformed males. Instead, they began to court them. These results show that it is possible to completely reverse normal behavioral responses by presenting males with unanticipated and conflicting sensory cues.
"Future studies will aim at unraveling the neuronal circuitry that governs this type of decision-making behavior, as such decisions are essential for survival," says Kravitz. "With the powerful genetic methods available in fly neurobiology, it should be possible to dissect the decision-making circuitry at far greater levels of detail than have heretofore been possible in other species."
"This study addresses a classic question in animal behavior: What motivates an individual to do X rather than Y, or vice versa," said Laurie Tompkins, Ph.D., who manages Kravitz's and other behavioral genetics grants at the National Institutes of Health. "Because the general principles of how behaviors are controlled are conserved among species, Kravitz's conclusions about how flies make simple choices may illuminate how humans and other animals make more complex decisions."
Notes:
The study was supported by grants from the National Institute of General Medical Science and by a Pew Latin American Fellowship awarded to FernГЎndez.
Written by Ann Marie Menting.
CITATION: PLoS Biology, 8(11): e1000541; doi:10.1371/journal.pbio.1000541, Nov 23, 2010
"Pheromonal and Behavioral Cues Trigger Male-to-Female Aggression in Drosophila"
MarГa de la Paz FernГЎndez (1), Yick-Bun Chan (1), Joanne Y. Yew (2,3,4), Jean-Christophe Billeter (5), Klaus Dreisewerd (3), Joel D. Levine (5), Edward A. Kravitz (1)
(1) Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
(2) Temasek Life Sciences Laboratories, 1 Research Linkn National University of Singapore, Singapore
(3) Institute of Medical Physics and Biophysics, Westfälische Wilhelms-Universität Münster, Münster, Germany
(4) Department of Biological Sciences, National University of Singapore, Singapore
(5) Department of Biology, University of Toronto at Mississauga, Mississauga, Ontario, Canada
Source:
David Cameron
Harvard Medical School
Like most animals, fruit flies must distinguish between a potential mate and a potential competitor. When a male fruit fly suspects he's encountered a female, he'll court; when he senses the other is a male, he'll fight. What triggers these sex-specific responses?
According to new research by scientists at Harvard Medical School, the answer lies with both pheromonal profiles and behavioral patterns. The researchers investigated the effects of taste and action by manipulating a gene that governs both the sex specificity of a fruit fly's body-surface hydrocarbons, or pheromones, and the sex-linked behavioral cues that issue through the dense nerve-cell network that constitutes the fly's brain.
"These findings underscore the importance of behavioral feedback in the manifestation of aggression," says Edward Kravitz, the George Packer Berry Professor of Neurobiology at Harvard Medical School.
The research is published in the November 23 issue of PLoS Biology.
MarГa de la Paz FernГЎndez and Yick-Bun Chan, post-doctoral researchers in the Kravitz lab, discovered these links to aggression when investigating whether a male fruit fly would ever attack a female. They focused on a particular gene called transformer, which is active in females but not in males. Through blocking transformer expression in a variety of different tissues in females, the researchers could specifically alter the "femaleness" or "maleness" of the pheromones, which in turn altered the patterns of aggressive behavior encoded in the fly's brain.
When they changed pheromone profiles so that females "tasted" like males, the researchers found that males would attack them. This indicated that pheromonal cues alone could label another fly as a competitor. But the researchers were surprised to discover that males also attacked "aggressive females" - flies that still looked, smelled and tasted female but had been genetically altered to display male-like patterns of behavior.
When the researchers turned the tables by triggering the expression of transformer in males so as to feminize both the pheromonal and behavioral profiles, control males showed no aggression toward the transformed males. Instead, they began to court them. These results show that it is possible to completely reverse normal behavioral responses by presenting males with unanticipated and conflicting sensory cues.
"Future studies will aim at unraveling the neuronal circuitry that governs this type of decision-making behavior, as such decisions are essential for survival," says Kravitz. "With the powerful genetic methods available in fly neurobiology, it should be possible to dissect the decision-making circuitry at far greater levels of detail than have heretofore been possible in other species."
"This study addresses a classic question in animal behavior: What motivates an individual to do X rather than Y, or vice versa," said Laurie Tompkins, Ph.D., who manages Kravitz's and other behavioral genetics grants at the National Institutes of Health. "Because the general principles of how behaviors are controlled are conserved among species, Kravitz's conclusions about how flies make simple choices may illuminate how humans and other animals make more complex decisions."
Notes:
The study was supported by grants from the National Institute of General Medical Science and by a Pew Latin American Fellowship awarded to FernГЎndez.
Written by Ann Marie Menting.
CITATION: PLoS Biology, 8(11): e1000541; doi:10.1371/journal.pbio.1000541, Nov 23, 2010
"Pheromonal and Behavioral Cues Trigger Male-to-Female Aggression in Drosophila"
MarГa de la Paz FernГЎndez (1), Yick-Bun Chan (1), Joanne Y. Yew (2,3,4), Jean-Christophe Billeter (5), Klaus Dreisewerd (3), Joel D. Levine (5), Edward A. Kravitz (1)
(1) Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
(2) Temasek Life Sciences Laboratories, 1 Research Linkn National University of Singapore, Singapore
(3) Institute of Medical Physics and Biophysics, Westfälische Wilhelms-Universität Münster, Münster, Germany
(4) Department of Biological Sciences, National University of Singapore, Singapore
(5) Department of Biology, University of Toronto at Mississauga, Mississauga, Ontario, Canada
Source:
David Cameron
Harvard Medical School
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