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
суббота, 25 июня 2011 г.
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
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