A University of Iowa researcher and colleagues at the University of Michigan have discovered a direct link between disruption of a critical cellular housekeeping process and fatty liver disease, a condition that causes fat to accumulate in the liver.
The findings, published in the Dec. 9 issue of the journal Developmental Cell, might open new avenues for understanding and perhaps treating fatty liver disease, which is the most common form of liver disease in the Western world and may affect as many as one in three American adults. Although fatty liver itself does not necessarily cause illness, it is associated with serious conditions like diabetes, metabolic syndrome, cirrhosis of the liver and liver failure.
The study, led by Tom Rutkowski, Ph.D., assistant professor of anatomy and cell biology at the UI Roy J. and Lucille A. Carver College of Medicine, and Randal Kaufman, Ph.D., professor of biological chemistry and internal medicine at the University of Michigan Medical School, shows that disrupted protein folding causes fatty liver in mice. The finding is the first to demonstrate a direct link between this form of cellular stress and abnormal fat metabolism.
Protein folding, which occurs in a cellular compartment called the endoplasmic reticulum (ER), is a vital cellular process because proteins must be correctly folded into defined three-dimensional shapes in order to function. Unfolded or misfolded proteins are a sign of cellular stress and can cause serious problems -- misfolded proteins cause amyloid plaques found in Alzheimer's disease. Cells rely on a very sensitive system known as the unfolded protein response (UPR) to guard against the cellular stress caused by protein folding problems.
To investigate how cells adapt to stress, the researchers created mice that were missing one component of the UPR. Under normal conditions, mice with the genetic mutation looked and behaved normally. However, the mutated mice were much less able to cope with cellular stress caused by disrupted protein folding than wild-type mice. In addition, the team found that protein misfolding caused fatty liver in mice with the mutation.
"We did not set out to understand fatty liver disease," said Rutkowski, who was a postdoctoral researcher in Kaufman's University of Michigan lab when the study was done. "We were really trying to understand the basic biology of how cells respond to stress, and through our approach to that fundamental question we were able to identify a connection to a condition that is of enormous importance to human health.
"When we realized that our experiments to investigate protein folding abnormalities were producing fatty liver disease as a consequence, it tied in with previous circumstantial evidence suggesting that ER stress might be involved in the liver's role in fat metabolism," he added.
The researchers followed up on the result and found that mice also developed fatty liver if their ability to fold proteins in the ER was genetically impaired, even when the UPR was functionally intact. This result suggested that the UPR is able to protect the liver against ER stress to a certain degree, but that fatty liver will result when the stress is too severe.
Further analysis of the mice models identified some of the genes that connect prolonged ER stress with faulty fat metabolism in the liver. In particular, the team found that unresolved ER stress leads to persistent expression of a gene called CHOP and that leads to changes in expression of fat metabolism genes. Mice with no CHOP were partially protected from fatty liver.
The results suggest that it is not disruption of a specific protein that caused fatty liver, but rather anything that perturbs the ER's ability to fold proteins correctly that is important. If this finding holds true for fatty liver disease in humans, therapies aimed at improving protein folding in the ER, or inhibiting CHOP, could help treat the condition.
"Our study does prove that perturbing protein folding can lead to fatty liver," Rutkowski said. "The next step is to investigate whether real physiological stresses like chronic alcohol consumption, obesity and viral infection also lead to fatty liver disease through protein folding problems in the ER."
In addition to Rutkowski and Kaufman, who also is a Howard Hughes Medical Institute investigator, key members of the research team included Jun Wu, Ph.D., who was a graduate student at University of Michigan Medical Center, and Mahmood Hussain, Ph.D., at State University of New York Downstate Medical Center. Researchers from the University of Michigan Medical Center; the University of Washington, Seattle, Wash.; and Wayne State University, Detroit, Mich., also were involved in the study.
The study was funded in part by the National Institutes of Health
Source: Jennifer Brown
University of Iowa
суббота, 29 октября 2011 г.
среда, 26 октября 2011 г.
DNA-based molecular nano-wires
An international consortium of 7 universities and research centres are seeking an alternative to silicon-based microelectronics in using molecules of DNA, which could enable a reduction in size of the current systems by a thousand times. The University of the Basque Country (UPV/EHU) is participating in this project through the research group led by Professor ?ngel Rubio Secades of the Department of Materials Physics.
The really innovative nature of this project lies, on the one hand, in the use of all the recognition and self-assembly potential of biological systems, more specifically, using derivatives of DNA such as G4-DNA, M-DNA and PC-DNA with a greater electronic potential than DNA itself (which is by itself an insulator).
On the other, it lies in carrying out studies in surface chemistry combined with scanning probe microscopy (SPM) and spectroscopy, the measurement of electrical transport, sophisticated nano-manufacture and theoretical studies of the computational simulation of the stability and properties of synthesised devices and/or motivating new structures that might have a greater potential. In this way the manner of designing nano-wires using these molecular derivatives is being developed.
As is the way of controlling the interaction between the molecular electrode and the molecular substrate, seeking a deep understanding of the energy conduction mechanisms of these nano-wires and being able to produce models of nanomolecular devices based on these DNA derivatives.
This release is also available in Spanish.
Garazi Andonegi
garazielhuyar
34-943-363-040
Elhuyar Fundazioa
basqueresearch
The really innovative nature of this project lies, on the one hand, in the use of all the recognition and self-assembly potential of biological systems, more specifically, using derivatives of DNA such as G4-DNA, M-DNA and PC-DNA with a greater electronic potential than DNA itself (which is by itself an insulator).
On the other, it lies in carrying out studies in surface chemistry combined with scanning probe microscopy (SPM) and spectroscopy, the measurement of electrical transport, sophisticated nano-manufacture and theoretical studies of the computational simulation of the stability and properties of synthesised devices and/or motivating new structures that might have a greater potential. In this way the manner of designing nano-wires using these molecular derivatives is being developed.
As is the way of controlling the interaction between the molecular electrode and the molecular substrate, seeking a deep understanding of the energy conduction mechanisms of these nano-wires and being able to produce models of nanomolecular devices based on these DNA derivatives.
This release is also available in Spanish.
Garazi Andonegi
garazielhuyar
34-943-363-040
Elhuyar Fundazioa
basqueresearch
воскресенье, 23 октября 2011 г.
Genetic map of human diversity completed, hope for cure of many diseases
We all share 99.9% of each other's genes, the remaining 0.1% is what makes some of us more susceptible to diseases such as Alzheimer's, Cancer, Diabetes, Heart Disease and a vast array of other conditions.
A couple of hundred scientists from various countries have spent the last few years working away at trying to identify the genetic differences between people. They have been trying to break down the human genome.
269 volunteers were involved in this fete. Some of them came from the Yoruba tribe, Nigeria, others were citizens of Tokyo, Japan, from Beijing, China and European Americans from Utah, USA. The geneticists analysed these people's DNA and built up a map of their genetic diversity (a map showing their genetic differences). The map is based on haplotypes. Haplotypes are large chunks of DNA that contain a unique battery of single mutations - these mutations are inherited together in identical blocks.
The map is called a HapMap (Hap is taken from the word Haplotypes). The scientists have managed to identify and map over one million single mutations to their haplotypes.
Now, the scientists can make comparisons between groups of people who are susceptible to certain diseases and those that are not. They do this by using the HapMap. We will be able to find the genes that cause certain diseases to happen much more quickly as a result of this work, say the scientists - 20 times more quickly, they say.
You can read all about this in the coming issue of Nature, October 27th, 2005.
: Christian
Editor: blog
A couple of hundred scientists from various countries have spent the last few years working away at trying to identify the genetic differences between people. They have been trying to break down the human genome.
269 volunteers were involved in this fete. Some of them came from the Yoruba tribe, Nigeria, others were citizens of Tokyo, Japan, from Beijing, China and European Americans from Utah, USA. The geneticists analysed these people's DNA and built up a map of their genetic diversity (a map showing their genetic differences). The map is based on haplotypes. Haplotypes are large chunks of DNA that contain a unique battery of single mutations - these mutations are inherited together in identical blocks.
The map is called a HapMap (Hap is taken from the word Haplotypes). The scientists have managed to identify and map over one million single mutations to their haplotypes.
Now, the scientists can make comparisons between groups of people who are susceptible to certain diseases and those that are not. They do this by using the HapMap. We will be able to find the genes that cause certain diseases to happen much more quickly as a result of this work, say the scientists - 20 times more quickly, they say.
You can read all about this in the coming issue of Nature, October 27th, 2005.
: Christian
Editor: blog
четверг, 20 октября 2011 г.
Blocking Cancer-Causing Gene Improves Radiation Effectiveness, Jefferson Researchers Find
Inhibiting a particular cancer-causing gene can enhance the cell-killing effects of radiation, a team of radiation oncologists and cancer biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia has found.
Adam Dicker, M.D., Ph.D., professor of radiation oncology at Jefferson Medical College and his co-workers used an increasingly common animal model, the zebrafish, and antisense technology to show that the drug flavopiridol works by blocking the activity of the gene, cyclin D1, which is made in excessive amounts in about half of all breast cancers. Using similar techniques in the future, the scientists say, may enable researchers to better gauge the effects of drugs.
According to Dr. Dicker, flavopiridol was found to inhibit cyclins, a family of genes vital to cell functioning. When it was initially tested in clinical trials, it was found to be toxic in humans. But in the laboratory, it added to the cell-killing effects of ionizing radiation, which is used to treat cancer. No one was sure why.
To find out, Dr. Dicker and his group turned to zebrafish. If they understood how the drug was causing toxicity, they or someone else could potentially design molecular copycat drugs that worked just as well, but were less toxic.
"Zebrafish enabled us to add a vertebrate system to examine both efficacy and toxicity issues," he notes. They reported their findings November 7, 2006 at the annual meeting of the American Society for Therapeutic Radiology and Oncology in Philadelphia.
In the work, Dr. Dicker and his co-workers first showed that flavopiridol-treated zebrafish embryos were much more sensitive than normal zebrafish to the effects of radiation. Then, believing that this effect stemmed from the drug's ability to block cyclin D, they used antisense technology to "knock down" - reduce the expression of - several cyclin genes, including cyclin D1.
Antisense DNA drugs work by binding to RNA messages from a target gene. The genetic code in the RNA cannot be read, essentially turning off the gene.
"We think that the radiosensitization is primarily due to cyclin D1," Dr. Dicker says. "We were able to genetically reduce the amount of cyclin D1 through the antisense technology, and when compared to embryos treated with radiation and flavopiridol, we saw that the effects were essentially identical. This shows the power of the system. Flavopiridol hits five or six cyclins and this allows us to find which cyclins are responsible for the radiosensitive effects.
"Theoretically, if we had a drug that inhibited several cyclins, we could understand the effect of inhibiting each cyclin by knocking it down with antisense," he says. "The technique helps explain drug function."
Contact: Steve Benowitz
Thomas Jefferson University
Adam Dicker, M.D., Ph.D., professor of radiation oncology at Jefferson Medical College and his co-workers used an increasingly common animal model, the zebrafish, and antisense technology to show that the drug flavopiridol works by blocking the activity of the gene, cyclin D1, which is made in excessive amounts in about half of all breast cancers. Using similar techniques in the future, the scientists say, may enable researchers to better gauge the effects of drugs.
According to Dr. Dicker, flavopiridol was found to inhibit cyclins, a family of genes vital to cell functioning. When it was initially tested in clinical trials, it was found to be toxic in humans. But in the laboratory, it added to the cell-killing effects of ionizing radiation, which is used to treat cancer. No one was sure why.
To find out, Dr. Dicker and his group turned to zebrafish. If they understood how the drug was causing toxicity, they or someone else could potentially design molecular copycat drugs that worked just as well, but were less toxic.
"Zebrafish enabled us to add a vertebrate system to examine both efficacy and toxicity issues," he notes. They reported their findings November 7, 2006 at the annual meeting of the American Society for Therapeutic Radiology and Oncology in Philadelphia.
In the work, Dr. Dicker and his co-workers first showed that flavopiridol-treated zebrafish embryos were much more sensitive than normal zebrafish to the effects of radiation. Then, believing that this effect stemmed from the drug's ability to block cyclin D, they used antisense technology to "knock down" - reduce the expression of - several cyclin genes, including cyclin D1.
Antisense DNA drugs work by binding to RNA messages from a target gene. The genetic code in the RNA cannot be read, essentially turning off the gene.
"We think that the radiosensitization is primarily due to cyclin D1," Dr. Dicker says. "We were able to genetically reduce the amount of cyclin D1 through the antisense technology, and when compared to embryos treated with radiation and flavopiridol, we saw that the effects were essentially identical. This shows the power of the system. Flavopiridol hits five or six cyclins and this allows us to find which cyclins are responsible for the radiosensitive effects.
"Theoretically, if we had a drug that inhibited several cyclins, we could understand the effect of inhibiting each cyclin by knocking it down with antisense," he says. "The technique helps explain drug function."
Contact: Steve Benowitz
Thomas Jefferson University
понедельник, 17 октября 2011 г.
BRIT1 Allows DNA Repair Teams Access To Damaged Sites
Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.
Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows that BRIT1 connects with another protein complex to relax DNA's tight packaging at the site of the damage.
"Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.
BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the protein plays a key role in early detection of DNA damage.
Chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin. Chromatin is a very condensed structure that forms a natural barrier inhibiting access to genes, said first author Guang Peng, Ph.D., a post-doctoral fellow in Systems Biology. ATP-dependent chromatin remodeling is a fundamental mechanism used by cells to relax chromatin in DNA repair, but the detailed molecular mechanism by which it is recruited to DNA lesions in response to damage signaling has been largely unknown.
BRIT1 summons help
"Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair," Peng said.
A series of lab experiments showed that BRIT1 accomplishes this by enhanced binding to a known chromatin remodeling complex called SWI-SNF when a specific site on the complex is phosphorylated. BRIT1 also maintains the relaxation factor at the damage site.
The team showed that normal BRIT1 aids repair of double-stranded DNA breaks by allowing access to two repair pathways: homologous recombination (HR) and non-homologous end-joining (NHEC).
DNA repair efficiency dropped by between 40 and 60 percent in cells with BRIT1 knocked down that were then exposed to ionizing radiation, allowing many damaged cells to divide and pass on their genetic defects.
Potential for cancer treatment
Having shown that BRIT1 deficiency impairs HR repair, Peng said one solution the team is examining is to treat cancer cells lacking BRIT1 with PARP inhibitors, drugs that specifically kill HR-deficient cancer cells.
BRIT1 mutations are known to cause a neurological condition called primary microcephaly, in which the brain develops to only one third of normal size. The team showed that in experiments using cells derived from primary microcephaly patients that BRIT1 dysfunction may specifically contribute to development of the neurological disease by failing to bind to SWI-SNF to relax chromatin.
The research was funded by grants from the National Cancer Institute and an American Cancer Society Research Scholar Award.
Co-authors with Lin and Peng are: Eon-Kyoung Yim, Hui Dai, Mei-Ren Pan, Ph.D., Ruozhen Hu, all of M. D. Anderson's Department of Systems Biology; Hu is also a student in the University of Texas Graduate School of Biomedical Sciences; Andrew Jackson, Ph.D., of MRC Human Genetics Unit, Western General Hospital in Edinburgh; Ineke van der Burgt, Ph.D., Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, Netherlands; Kaiyi Li, Ph.D., Department of Surgery, Baylor College of Medicine.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
Source: University of Texas M. D. Anderson Cancer Center
Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows that BRIT1 connects with another protein complex to relax DNA's tight packaging at the site of the damage.
"Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.
BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the protein plays a key role in early detection of DNA damage.
Chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin. Chromatin is a very condensed structure that forms a natural barrier inhibiting access to genes, said first author Guang Peng, Ph.D., a post-doctoral fellow in Systems Biology. ATP-dependent chromatin remodeling is a fundamental mechanism used by cells to relax chromatin in DNA repair, but the detailed molecular mechanism by which it is recruited to DNA lesions in response to damage signaling has been largely unknown.
BRIT1 summons help
"Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair," Peng said.
A series of lab experiments showed that BRIT1 accomplishes this by enhanced binding to a known chromatin remodeling complex called SWI-SNF when a specific site on the complex is phosphorylated. BRIT1 also maintains the relaxation factor at the damage site.
The team showed that normal BRIT1 aids repair of double-stranded DNA breaks by allowing access to two repair pathways: homologous recombination (HR) and non-homologous end-joining (NHEC).
DNA repair efficiency dropped by between 40 and 60 percent in cells with BRIT1 knocked down that were then exposed to ionizing radiation, allowing many damaged cells to divide and pass on their genetic defects.
Potential for cancer treatment
Having shown that BRIT1 deficiency impairs HR repair, Peng said one solution the team is examining is to treat cancer cells lacking BRIT1 with PARP inhibitors, drugs that specifically kill HR-deficient cancer cells.
BRIT1 mutations are known to cause a neurological condition called primary microcephaly, in which the brain develops to only one third of normal size. The team showed that in experiments using cells derived from primary microcephaly patients that BRIT1 dysfunction may specifically contribute to development of the neurological disease by failing to bind to SWI-SNF to relax chromatin.
The research was funded by grants from the National Cancer Institute and an American Cancer Society Research Scholar Award.
Co-authors with Lin and Peng are: Eon-Kyoung Yim, Hui Dai, Mei-Ren Pan, Ph.D., Ruozhen Hu, all of M. D. Anderson's Department of Systems Biology; Hu is also a student in the University of Texas Graduate School of Biomedical Sciences; Andrew Jackson, Ph.D., of MRC Human Genetics Unit, Western General Hospital in Edinburgh; Ineke van der Burgt, Ph.D., Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, Netherlands; Kaiyi Li, Ph.D., Department of Surgery, Baylor College of Medicine.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
Source: University of Texas M. D. Anderson Cancer Center
пятница, 14 октября 2011 г.
NYT Examines Challenges To Improving 'Personalized Medicine' For Breast Cancer, Other Diseases
The New York Times on Tuesday examined how improvements in genetic testing could affect "personalized medicine" for the treatment of breast cancer and other diseases in the future. Personalized medicine uses genetic screening and other tests to provide physicians with more information to tailor patients' treatments, the Times reports. Experts believe that most drugs currently on the market work for only about half of patients who take them, meaning that "much of the nation's approximately $300 billion annual drug spending [is] wasted," and "countless patients are being exposed unnecessarily to side effects," according to the Times. The Times reports that personalized medicine would "go beyond" the "one-size-fits-all" approach of conventional research studies -- in which the "winning treatment [is] recommended for everybody" -- by determining the best treatments for individual patients, rather than treating all patients the same "in hopes of benefiting the fortunate few." However, there is no universally recognized method for evaluating genetic tests, and many can be marketed without FDA approval.
The Times reports that the breast cancer treatment tamoxifen -- a generic drug used to prevent the recurrence of tumors -- "illustrates the promise and current limitations of genetic testing." A 2003 study led by the Indiana University School of Medicine's David Flockhart demonstrated that tamoxifen is converted through the CYP2D6 enzyme -- also known as 2D6 -- into another substance called endoxifen, which is what actually exerts the cancer-fighting effect. However, the enzyme has different levels of activity in different people because of variations in individuals' 2D6 genes, according to Flockhart. He said that up to 7% of people have an inactive enzyme, depending on their ethnicity, and an additional 20% to 40% have a modestly active enzyme. For these individuals, tamoxifen would offer little or no protection against tumors because the patients' bodies could not convert the drug into endoxifen. Currently, most US patients are treated with aromatase inhibitors -- a more expensive, newer class of drugs that cost about $18,000 over five years, compared with $500 for tamoxifen. Aromatase inhibitors performed better than tamoxifen in clinical trials conducted "before the role of 2D6 was generally understood," the Times reports. However, those trials might have found that tamoxifen worked as well or better than the newer drugs if only women with active 2D6 were included, according to researchers at the Dana-Faber Cancer Institute.
The Times reports that "proving these suppositions and having them incorporated into medical practice have not been easy." Tests are available to detect the 2D6 genes of individual patients for about $300, but many experts are hesitant to use the tests because of conflicting study results examining the relationship between tamoxifen and the genes. In addition, there are dozens of variants of the 2D6 gene, and laboratories can differ in how they interpret test results. There also are no clear guidelines for how doctors should act upon the information provided by the test. Drug maker Genentech has petitioned FDA to regulate the tests, and the agency in a meeting last month said that clinical trials would be the best way to validate the tests. However, developers of the tests say that new trials would be too expensive and time-consuming, "so many tests are validated by reanalyzing patient data from old trials," the Times reports. For example, a 2005 study by Matthew Goetz and colleagues at the Mayo Clinic analyzed stored tumor samples from an old trial of breast cancer patients to test the 2D6 genes of each patient. The study found that 32% of women with inactive 2D6 enzymes had relapsed or died within two years, compared with only 2% of women with active enzymes.
Experts also point to other "formidable obstacles on the path to the promised land of personalized medicine," according to the Times. The ability of test developers to prove that their tests are accurate and useful is one major obstacle. Other obstacles include the reluctance of drugmakers to encourage or develop tests that could limit the use of their drugs and the possibility that insurers might not pay for the tests. However, drugmakers are "starting to realize that their medicines might not be approved for paid or without better evidence that they work," according to the Times (Pollack, New York Times, 12/30/08).
Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women's Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women's Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.
© 2008 The Advisory Board Company. All rights reserved.
The Times reports that the breast cancer treatment tamoxifen -- a generic drug used to prevent the recurrence of tumors -- "illustrates the promise and current limitations of genetic testing." A 2003 study led by the Indiana University School of Medicine's David Flockhart demonstrated that tamoxifen is converted through the CYP2D6 enzyme -- also known as 2D6 -- into another substance called endoxifen, which is what actually exerts the cancer-fighting effect. However, the enzyme has different levels of activity in different people because of variations in individuals' 2D6 genes, according to Flockhart. He said that up to 7% of people have an inactive enzyme, depending on their ethnicity, and an additional 20% to 40% have a modestly active enzyme. For these individuals, tamoxifen would offer little or no protection against tumors because the patients' bodies could not convert the drug into endoxifen. Currently, most US patients are treated with aromatase inhibitors -- a more expensive, newer class of drugs that cost about $18,000 over five years, compared with $500 for tamoxifen. Aromatase inhibitors performed better than tamoxifen in clinical trials conducted "before the role of 2D6 was generally understood," the Times reports. However, those trials might have found that tamoxifen worked as well or better than the newer drugs if only women with active 2D6 were included, according to researchers at the Dana-Faber Cancer Institute.
The Times reports that "proving these suppositions and having them incorporated into medical practice have not been easy." Tests are available to detect the 2D6 genes of individual patients for about $300, but many experts are hesitant to use the tests because of conflicting study results examining the relationship between tamoxifen and the genes. In addition, there are dozens of variants of the 2D6 gene, and laboratories can differ in how they interpret test results. There also are no clear guidelines for how doctors should act upon the information provided by the test. Drug maker Genentech has petitioned FDA to regulate the tests, and the agency in a meeting last month said that clinical trials would be the best way to validate the tests. However, developers of the tests say that new trials would be too expensive and time-consuming, "so many tests are validated by reanalyzing patient data from old trials," the Times reports. For example, a 2005 study by Matthew Goetz and colleagues at the Mayo Clinic analyzed stored tumor samples from an old trial of breast cancer patients to test the 2D6 genes of each patient. The study found that 32% of women with inactive 2D6 enzymes had relapsed or died within two years, compared with only 2% of women with active enzymes.
Experts also point to other "formidable obstacles on the path to the promised land of personalized medicine," according to the Times. The ability of test developers to prove that their tests are accurate and useful is one major obstacle. Other obstacles include the reluctance of drugmakers to encourage or develop tests that could limit the use of their drugs and the possibility that insurers might not pay for the tests. However, drugmakers are "starting to realize that their medicines might not be approved for paid or without better evidence that they work," according to the Times (Pollack, New York Times, 12/30/08).
Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women's Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women's Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.
© 2008 The Advisory Board Company. All rights reserved.
вторник, 11 октября 2011 г.
Link Between Mutations In Gene And Ciliopathies
An international team of scientists, led by researchers at the University of California, San Diego School of Medicine, have discovered a connection between mutations in the INPP5E gene and ciliopathies. Their findings, which may lead to new therapies for these diseases, appear in the online edition of Nature Genetics.
Ciliopathies are a newly emerging group of diseases caused by defects in the function or structure of cellular primary cilia, which are small, cellular appendages of previously unknown function. Examples of ciliopathies include mental retardation, retinal blindness, obesity, polycystic kidney disease, liver fibrosis, ataxia, and some forms of cancer.
Joseph G. Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego and a Howard Hughes Medical Institute investigator, and his colleagues showed that when two copies of mutated INPP5E are present in an individual, the result is Joubert syndrome, a condition marked by mental retardation and impaired balance. They linked the function of the protein that is encoded by this gene to enzymatic conversion of one of the most important signaling molecules in the body, phosphatylinositol, currently one of the main targets of the pharmaceutical industry to treat a host of diseases, including cancer.
The Gleeson team, led by UC San Diego scientists Stephanie Bielas, PhD, and Jennifer Silhavey, MS, discovered that the enzyme goes to a cellular structure known as the cilium, a long-forgotten organelle without clear function until recently. However, in the past five years, the field of cilia biology has exploded due to the recognition that many of our basic bodily functions are regulated and "fine-tuned" by the cilium.
Because all of the genetic mutations led to an alteration in the enzyme activity, it suggests that the phosphatylinositol pathway could be modulated using drugs already in the pharmaceutical pipeline in order to target a host of cilia-related diseases, to re-establish the normal pathway function and improve the diverse symptoms of ciliopathies.
"Many patients show symptoms that worsen over time," said Gleeson. "It is possible that if effective treatments were available, they could stop or possibly reverse the course of the disease, and prenatal testing could be made available for patients at risk for these conditions."
Currently, existing treatments for ciliopathies are only to ease symptoms. However, according to Gleeson there is recent evidence that one new drug, roscovitine, could arrest polycystic kidney disease, which suggests that similar therapeutical approaches may be helpful in treating other ciliopathies.
One of the most exciting aspects of cilia disease is the connection with obesity. It is possible that modulation of these pathways could represent new avenues to explore for weight control, according to Gleeson.
Notes:
Contributors to the discovery include co-first authors Stephanie L. Bielas and Jennifer L. Silhavy of UC San Diego; Francesco Brancati of the Casa Sollievo della Sofferenza-Mendel Institute and G. d'Annunzio University Foundation, Italy; Marina V. Kisseleva of the Washington University School of Medicine; Lihadh Al-Gazali of the United Arab Emirates University, United Arab Emirates; Laszlo Sztriha of the University of Szeged, Hungary; Riad A. Bayoumi of Sultan Qaboos University, Sultanate of Oman; Maha S. Zaki of the National Research Centre, Egypt; Alice Abdel-Aleem of the National Research Centre, Egypt; Ozgur Rosti of Istanbul University, Turkey; Hulya Kayserili of Istanbul University, Turkey; Dominika Swistun, Lesley Scott and Seth J. Field of UC San Diego; Enrico Bertini of the Bambino Gesu Children's Research Hospital, Italy; Eugen Boltshauser of the University Children's Hospital of Zurich, Switzerland; Elisa Fazzi of the Instituto di Ricovero e Cura a Carattere Scientifico C. Mondino Institute of Neurology, Italy; Lorena Travaglini of the Casa Sollievo della Sofferenza-Mendel Institute, Italy; Stephanie Gayral, Monique Jacoby and Stephane Schurmans of the Universite Libre de Bruxelles, Belgium; Bruno Dallapiccola of the Casa Sollievo della Sofferenza-Mendel Institute and Sapienza University, Italy; Philip W. Majerus of the Washington University School of Medicine; and Enza Maria Valente of the Casa Sollievo della Sofferenza-Mendel Institute and University of Messina, Italy.
The research was supported in part by grants from the National Institutes of Health, the Italian Ministry of Health, the Telethon Foundation Italy, the American Heart Association, the National Institute of Neurological Disorder and Stroke, the Burroughs Wellcome Fund, the March of Dimes and the Howard Hughes Medical Institute.
Source:
Debra Kain
University of California - San Diego
Ciliopathies are a newly emerging group of diseases caused by defects in the function or structure of cellular primary cilia, which are small, cellular appendages of previously unknown function. Examples of ciliopathies include mental retardation, retinal blindness, obesity, polycystic kidney disease, liver fibrosis, ataxia, and some forms of cancer.
Joseph G. Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego and a Howard Hughes Medical Institute investigator, and his colleagues showed that when two copies of mutated INPP5E are present in an individual, the result is Joubert syndrome, a condition marked by mental retardation and impaired balance. They linked the function of the protein that is encoded by this gene to enzymatic conversion of one of the most important signaling molecules in the body, phosphatylinositol, currently one of the main targets of the pharmaceutical industry to treat a host of diseases, including cancer.
The Gleeson team, led by UC San Diego scientists Stephanie Bielas, PhD, and Jennifer Silhavey, MS, discovered that the enzyme goes to a cellular structure known as the cilium, a long-forgotten organelle without clear function until recently. However, in the past five years, the field of cilia biology has exploded due to the recognition that many of our basic bodily functions are regulated and "fine-tuned" by the cilium.
Because all of the genetic mutations led to an alteration in the enzyme activity, it suggests that the phosphatylinositol pathway could be modulated using drugs already in the pharmaceutical pipeline in order to target a host of cilia-related diseases, to re-establish the normal pathway function and improve the diverse symptoms of ciliopathies.
"Many patients show symptoms that worsen over time," said Gleeson. "It is possible that if effective treatments were available, they could stop or possibly reverse the course of the disease, and prenatal testing could be made available for patients at risk for these conditions."
Currently, existing treatments for ciliopathies are only to ease symptoms. However, according to Gleeson there is recent evidence that one new drug, roscovitine, could arrest polycystic kidney disease, which suggests that similar therapeutical approaches may be helpful in treating other ciliopathies.
One of the most exciting aspects of cilia disease is the connection with obesity. It is possible that modulation of these pathways could represent new avenues to explore for weight control, according to Gleeson.
Notes:
Contributors to the discovery include co-first authors Stephanie L. Bielas and Jennifer L. Silhavy of UC San Diego; Francesco Brancati of the Casa Sollievo della Sofferenza-Mendel Institute and G. d'Annunzio University Foundation, Italy; Marina V. Kisseleva of the Washington University School of Medicine; Lihadh Al-Gazali of the United Arab Emirates University, United Arab Emirates; Laszlo Sztriha of the University of Szeged, Hungary; Riad A. Bayoumi of Sultan Qaboos University, Sultanate of Oman; Maha S. Zaki of the National Research Centre, Egypt; Alice Abdel-Aleem of the National Research Centre, Egypt; Ozgur Rosti of Istanbul University, Turkey; Hulya Kayserili of Istanbul University, Turkey; Dominika Swistun, Lesley Scott and Seth J. Field of UC San Diego; Enrico Bertini of the Bambino Gesu Children's Research Hospital, Italy; Eugen Boltshauser of the University Children's Hospital of Zurich, Switzerland; Elisa Fazzi of the Instituto di Ricovero e Cura a Carattere Scientifico C. Mondino Institute of Neurology, Italy; Lorena Travaglini of the Casa Sollievo della Sofferenza-Mendel Institute, Italy; Stephanie Gayral, Monique Jacoby and Stephane Schurmans of the Universite Libre de Bruxelles, Belgium; Bruno Dallapiccola of the Casa Sollievo della Sofferenza-Mendel Institute and Sapienza University, Italy; Philip W. Majerus of the Washington University School of Medicine; and Enza Maria Valente of the Casa Sollievo della Sofferenza-Mendel Institute and University of Messina, Italy.
The research was supported in part by grants from the National Institutes of Health, the Italian Ministry of Health, the Telethon Foundation Italy, the American Heart Association, the National Institute of Neurological Disorder and Stroke, the Burroughs Wellcome Fund, the March of Dimes and the Howard Hughes Medical Institute.
Source:
Debra Kain
University of California - San Diego
суббота, 8 октября 2011 г.
New Reporting Guidelines For Genetic Risk Prediction Studies: GRIPS Statement
This week PLoS Medicine publishes the Genetic RIsk Prediction Studies (GRIPS) Statement, a checklist and guidance to help strengthen the reporting of genetic risk prediction studies.
Because progress in gene discovery for complex diseases is fuelling interest in the application of genetic risk models for clinical and public health practice, the number of studies assessing predictive ability is steadily increasing, but the quality and completeness of reporting varies. The GRIPS Statement (and accompanying explanation document) provides guidance to enhance the transparency of study reporting, thereby improving the synthesis and application of information from multiple studies that might differ in design, conduct, or analysis.
In order to encourage dissemination, PLoS Medicine is co-publishing this article with Annals of Internal Medicine, BMJ, Circulation: Cardiovascular Genetics, European Journal of Clinical Investigation, European Journal of Epidemiology, European Journal of Human Genetics, Genetics in Medicine, Genome Medicine, and Journal of Clinical Epidemiology.
Funding:
The workshop was sponsored by the US Centers for Disease Control and Prevention on behalf of the Human Genome Epidemiology Network (HuGENet). A. Cecile J.W. Janssens is financially supported by grants from the Erasmus University Medical Center Rotterdam, the Center for Medical Systems Biology in the framework of the Netherlands Genomics Initiative (NGI) and the VIDI grant of the Netherlands Organisation for Scientific Research (NWO). John P.A. Ioannidis: Tufts CTSI is supported by the National Institutes of Health/ National Center for Research Resources (UL1 RR025752). Opinions in this paper are those of the authors and do not necessarily represent the official position or policies of the Tufts CTSI. Julian Little holds a Canada Research Chair in Human Genome Epidemiology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Competing Interests: John P. A. Ioannidis is a member of the PLoS Medicine Editorial Board.
Citation:
"Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement"
Janssens ACJW, Ioannidis JPA, van Duijn CM, Little J, Khoury MJ, et al. (2011)
PLoS Med 8(3): e1000420. doi:10.1371/journal.pmed.1000420
Because progress in gene discovery for complex diseases is fuelling interest in the application of genetic risk models for clinical and public health practice, the number of studies assessing predictive ability is steadily increasing, but the quality and completeness of reporting varies. The GRIPS Statement (and accompanying explanation document) provides guidance to enhance the transparency of study reporting, thereby improving the synthesis and application of information from multiple studies that might differ in design, conduct, or analysis.
In order to encourage dissemination, PLoS Medicine is co-publishing this article with Annals of Internal Medicine, BMJ, Circulation: Cardiovascular Genetics, European Journal of Clinical Investigation, European Journal of Epidemiology, European Journal of Human Genetics, Genetics in Medicine, Genome Medicine, and Journal of Clinical Epidemiology.
Funding:
The workshop was sponsored by the US Centers for Disease Control and Prevention on behalf of the Human Genome Epidemiology Network (HuGENet). A. Cecile J.W. Janssens is financially supported by grants from the Erasmus University Medical Center Rotterdam, the Center for Medical Systems Biology in the framework of the Netherlands Genomics Initiative (NGI) and the VIDI grant of the Netherlands Organisation for Scientific Research (NWO). John P.A. Ioannidis: Tufts CTSI is supported by the National Institutes of Health/ National Center for Research Resources (UL1 RR025752). Opinions in this paper are those of the authors and do not necessarily represent the official position or policies of the Tufts CTSI. Julian Little holds a Canada Research Chair in Human Genome Epidemiology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Competing Interests: John P. A. Ioannidis is a member of the PLoS Medicine Editorial Board.
Citation:
"Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement"
Janssens ACJW, Ioannidis JPA, van Duijn CM, Little J, Khoury MJ, et al. (2011)
PLoS Med 8(3): e1000420. doi:10.1371/journal.pmed.1000420
среда, 5 октября 2011 г.
18 Honoured By National Academy Of Sciences For Major Contributions To Science
The National Academy of Sciences (NAS) will honor 18 individuals in 2009 with awards recognizing extraordinary scientific achievements in the areas of biology, chemistry, geology, astronomy, social sciences, psychology, and application of science for the public good.
The recipients for 2009 are:
GRAHAM ALLISON, Douglas Dillon Professor of Government and director of the Belfer Center for Science and International Affairs at Harvard's John F. Kennedy School of Government, is the recipient of the NAS AWARD FOR BEHAVIORAL RESEARCH RELEVANT TO THE PREVENTION OF NUCLEAR WAR. Allison is being honored for illuminating alternative ways of thinking about political decision making with special relevance to crises, including nuclear crises, as demonstrated in his groundbreaking ESSENCE OF DECISION and subsequent works. The award, established by the gift of William and Katherine Estes, comes with a $20,000 prize and recognizes basic research in any field of cognitive or behavioral science that uses rigorous formal and empirical methods to advance our understanding of issues relating to the risk of nuclear war.
CORNELIA I. BARGMANN, Howard Hughes Medical Institute investigator and Torsten N. Wiesel Professor at Rockefeller University, is the recipient of the RICHARD LOUNSBERY AWARD. Bargmann is being honored for her extraordinarily inventive and successful use of molecular and classical genetics to probe the individual nerve cell basis of behavior in C. ELEGANS. The Lounsbery Award -- consisting of a medal and a prize of $50,000 -- is awarded to French and American scientists in alternate years for extraordinary scientific achievement in biology and medicine. The award is supported by the Richard Lounsbery Foundation.
JONATHAN BECKWITH, American Cancer Society Professor in the department of microbiology and molecular genetics at Harvard University, will receive the SELMAN A. WAKSMAN AWARD IN MICROBIOLOGY. Beckwith is being honored for fundamental contributions to gene regulation, protein targeting and secretion, and disulfide biochemistry, and also for the development of gene fusions as an experimental tool. This award, established by the Foundation for Microbiology, recognizes excellence in the field of microbiology and comes with a prize of $5,000.
STEPHEN P. BELL, Howard Hughes Medical Institute investigator and professor of biology at the Massachusetts Institute of Technology, is the recipient of the NAS AWARD FOR MOLECULAR BIOLOGY. Bell is being honored for groundbreaking studies illuminating the mechanisms of DNA replication in eukaryotic cells. The award consists of a medal and a prize of $25,000, and is sponsored by Pfizer Inc.
CHARLES L. BENNETT, professor of physics and astronomy at Johns Hopkins University, is the recipient of the COMSTOCK PRIZE IN PHYSICS. Bennett is being honored for his mapping of the cosmic microwave background and determining the universe's age, mass-energy content, geometry, expansion rate, and reionization epoch with unprecedented precision. This prize of $20,000 is awarded for a recent innovative discovery or investigation in electricity, magnetism, or radiant energy.
ROBERT N. CLAYTON, Enrico Fermi Distinguished Service Professor Emeritus at the University of Chicago, will receive the J. LAWRENCE SMITH MEDAL. He is being honored for pioneering the study of oxygen isotopes to unravel the nature and origin of meteorites, showing that meteorites were assembled from components with distinct nuclear origins. The medal and a prize of $25,000 are awarded for recent original and meritorious investigations of meteoric bodies.
JOSEPH FELSENSTEIN, professor in the departments of genome sciences and biology at the University of Washington, is awarded the JOHN J. CARTY AWARD FOR THE ADVANCEMENT OF SCIENCE. Felsenstein is being honored for revolutionizing population genetics, phylogenetic biology, and systematics by developing a sophisticated computational framework to deduce evolutionary relationships of genes and species from molecular data. The Carty Award -- a medal and a prize of $25,000 awarded annually for noteworthy and distinguished accomplishment in any field of science -- is being presented in the area of evolution in 2009.
ALFRED G. FISCHER, professor emeritus in the department of geological sciences at the University of Southern California, is the recipient of the MARY CLARK THOMPSON MEDAL. He is being honored for leadership and research in the discovery of the cyclical and period nature of the sedimentary record in the geologic past and its connections with earth-system change, including biodiversity. This medal, with a prize of $15,000, is awarded to recognize important contributions to geology and paleontology.
JOANNA S. FOWLER, senior chemist in the department of medicine at Brookhaven National Laboratory, is awarded the NAS AWARD IN CHEMICAL SCIENCES. Fowler is being honored for exceptional accomplishments in the synthesis of positron-emitting chemical probes, and for their implementation in biomedical imaging and studies of IN VIVO biochemistry, which have had a major impact on human health worldwide. The medal and prize of $15,000 are given for innovative research in the chemical sciences that contributes to the better understanding of the natural sciences and to the benefit of humanity, and is supported by the Merck Company Foundation.
NEIL GEHRELS is the recipient of the HENRY DRAPER MEDAL. Gehrels, chief of the Astroparticle Physics Laboratory at the NASA/Goddard Space Flight Center, is being honored for his pioneering contributions to gamma ray astronomy. His leadership of the Compton Gamma Ray Observatory and the Swift Mission has led to new insights into the extreme physics of active galactic nuclei and gamma ray bursts. The Henry Draper Medal and a prize of $15,000 are awarded for an original investigation in astronomical physics.
ARTHUR R. GROSSMAN of the Carnegie Institution for Science is the recipient of the GILBERT MORGAN SMITH MEDAL. Grossman is being honored for pioneering creative and comprehensive research on algae and cyanobacteria, elucidating molecular mechanisms by which they adapt to changes in light color and to nutrient stress. The Gilbert Morgan Smith Medal and prize of $20,000 are awarded for excellence in published research on marine or freshwater algae.
ROGER W. HENDRIX of the University of Pittsburgh is awarded the NAS AWARD FOR SCIENTIFIC REVIEWING. Hendrix's reviews, overviews, and minireviews have focused research in the areas of structure, assembly, and genomics of bacteriophages and include numerous original and provocative ideas. The prize of $10,000 -- given in 2009 in the field of genetics -- acknowledges excellence in scientific reviewing within the past 10 years. The award is supported by ANNUAL REVIEWS, the Institute for Scientific Information, and THE SCIENTIST in honor of J. Murray Luck.
ALI JAVEY, assistant professor of electrical engineering and computer sciences at the University of California, Berkeley, is the recipient of the NAS AWARD FOR INITIATIVES IN RESEARCH. Javey is being recognized for seminal advances in carbon nanoelectronics, utilizing and synthesizing concepts from chemistry, physics, and engineering. The prize of $15,000 is awarded to recognize innovative young scientists and to encourage research likely to lead toward new capabilities for human benefit. The award -- established by AT&T Bell Laboratories in honor of William O. Baker and supported by Alcatel-Lucent -- is being presented in 2009 in the field of nanoscience.
TIRIN MOORE, assistant professor in the department of neurobiology at Stanford University School of Medicine, and ANDREW J. OXENHAM, assistant professor in the department of psychology at the University of Minnesota, will each receive a TROLAND RESEARCH AWARD. Moore is being honored for fundamental and insightful contributions to our understanding of the neuronal mechanisms that control directed visual attention. Oxenham is being honored for profound and rigorous contributions to our understanding of the relationship between auditory perception and its underlying physiological mechanisms. The Troland Research Awards are two research awards of $50,000 given annually to young investigators to recognize unusual achievement and to further their research within the broad spectrum of experimental psychology.
JOHN D. ROBERTS, Institute Professor of Chemistry Emeritus at the California Institute of Technology, is awarded the NAS AWARD FOR CHEMISTRY IN SERVICE TO SOCIETY. Roberts is being honored for seminal contributions in physical organic chemistry, in particular the introduction of NMR spectroscopy to the chemistry community. The award, consisting of a prize of $20,000, was established by E.I. du Pont de Nemours & Co.
KEITH W. TANTLINGER of Tantlinger Engineering is awarded the GIBBS BROTHERS MEDAL. Tantlinger is being honored for his visionary and innovative design of the cellular container ship and supporting systems that transformed the world's shipping fleet and facilitated the rapid expansion of global trade. The medal and prize of $20,000 are given for outstanding contributions in the field of naval architecture and marine engineering.
Also to be honored at the April 26 awards ceremony, which will take place during the Academy's 146th annual meeting, is NEAL F. LANE, Malcolm Gillis University Professor and senior fellow of the James A. Baker III Institute for Public Policy at Rice University, who was chosen to receive the PUBLIC WELFARE MEDAL. Lane, who served as assistant to the president for science and technology and director of the Office of Science and Technology Policy from 1998 to 2001, and as director of the National Science Foundation from 1993 to 1998, is honored for serving the scientific community in many executive and leadership roles and for his continuing efforts to advance and promote science and technology in the United States. The medal was established to recognize distinguished contributions in the application of science to the public welfare and has been presented since 1914.
The National Academy of Sciences is a private, nonprofit honorific society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Since 1863, the National Academy of Sciences has served to "investigate, examine, experiment, and report upon any subject of science or art" whenever called upon to do so by any department of the government.
[ This news release is available at NATIONAL-ACADEMIES ]
Source: Maureen O'Leary
National Academy of Sciences
The recipients for 2009 are:
GRAHAM ALLISON, Douglas Dillon Professor of Government and director of the Belfer Center for Science and International Affairs at Harvard's John F. Kennedy School of Government, is the recipient of the NAS AWARD FOR BEHAVIORAL RESEARCH RELEVANT TO THE PREVENTION OF NUCLEAR WAR. Allison is being honored for illuminating alternative ways of thinking about political decision making with special relevance to crises, including nuclear crises, as demonstrated in his groundbreaking ESSENCE OF DECISION and subsequent works. The award, established by the gift of William and Katherine Estes, comes with a $20,000 prize and recognizes basic research in any field of cognitive or behavioral science that uses rigorous formal and empirical methods to advance our understanding of issues relating to the risk of nuclear war.
CORNELIA I. BARGMANN, Howard Hughes Medical Institute investigator and Torsten N. Wiesel Professor at Rockefeller University, is the recipient of the RICHARD LOUNSBERY AWARD. Bargmann is being honored for her extraordinarily inventive and successful use of molecular and classical genetics to probe the individual nerve cell basis of behavior in C. ELEGANS. The Lounsbery Award -- consisting of a medal and a prize of $50,000 -- is awarded to French and American scientists in alternate years for extraordinary scientific achievement in biology and medicine. The award is supported by the Richard Lounsbery Foundation.
JONATHAN BECKWITH, American Cancer Society Professor in the department of microbiology and molecular genetics at Harvard University, will receive the SELMAN A. WAKSMAN AWARD IN MICROBIOLOGY. Beckwith is being honored for fundamental contributions to gene regulation, protein targeting and secretion, and disulfide biochemistry, and also for the development of gene fusions as an experimental tool. This award, established by the Foundation for Microbiology, recognizes excellence in the field of microbiology and comes with a prize of $5,000.
STEPHEN P. BELL, Howard Hughes Medical Institute investigator and professor of biology at the Massachusetts Institute of Technology, is the recipient of the NAS AWARD FOR MOLECULAR BIOLOGY. Bell is being honored for groundbreaking studies illuminating the mechanisms of DNA replication in eukaryotic cells. The award consists of a medal and a prize of $25,000, and is sponsored by Pfizer Inc.
CHARLES L. BENNETT, professor of physics and astronomy at Johns Hopkins University, is the recipient of the COMSTOCK PRIZE IN PHYSICS. Bennett is being honored for his mapping of the cosmic microwave background and determining the universe's age, mass-energy content, geometry, expansion rate, and reionization epoch with unprecedented precision. This prize of $20,000 is awarded for a recent innovative discovery or investigation in electricity, magnetism, or radiant energy.
ROBERT N. CLAYTON, Enrico Fermi Distinguished Service Professor Emeritus at the University of Chicago, will receive the J. LAWRENCE SMITH MEDAL. He is being honored for pioneering the study of oxygen isotopes to unravel the nature and origin of meteorites, showing that meteorites were assembled from components with distinct nuclear origins. The medal and a prize of $25,000 are awarded for recent original and meritorious investigations of meteoric bodies.
JOSEPH FELSENSTEIN, professor in the departments of genome sciences and biology at the University of Washington, is awarded the JOHN J. CARTY AWARD FOR THE ADVANCEMENT OF SCIENCE. Felsenstein is being honored for revolutionizing population genetics, phylogenetic biology, and systematics by developing a sophisticated computational framework to deduce evolutionary relationships of genes and species from molecular data. The Carty Award -- a medal and a prize of $25,000 awarded annually for noteworthy and distinguished accomplishment in any field of science -- is being presented in the area of evolution in 2009.
ALFRED G. FISCHER, professor emeritus in the department of geological sciences at the University of Southern California, is the recipient of the MARY CLARK THOMPSON MEDAL. He is being honored for leadership and research in the discovery of the cyclical and period nature of the sedimentary record in the geologic past and its connections with earth-system change, including biodiversity. This medal, with a prize of $15,000, is awarded to recognize important contributions to geology and paleontology.
JOANNA S. FOWLER, senior chemist in the department of medicine at Brookhaven National Laboratory, is awarded the NAS AWARD IN CHEMICAL SCIENCES. Fowler is being honored for exceptional accomplishments in the synthesis of positron-emitting chemical probes, and for their implementation in biomedical imaging and studies of IN VIVO biochemistry, which have had a major impact on human health worldwide. The medal and prize of $15,000 are given for innovative research in the chemical sciences that contributes to the better understanding of the natural sciences and to the benefit of humanity, and is supported by the Merck Company Foundation.
NEIL GEHRELS is the recipient of the HENRY DRAPER MEDAL. Gehrels, chief of the Astroparticle Physics Laboratory at the NASA/Goddard Space Flight Center, is being honored for his pioneering contributions to gamma ray astronomy. His leadership of the Compton Gamma Ray Observatory and the Swift Mission has led to new insights into the extreme physics of active galactic nuclei and gamma ray bursts. The Henry Draper Medal and a prize of $15,000 are awarded for an original investigation in astronomical physics.
ARTHUR R. GROSSMAN of the Carnegie Institution for Science is the recipient of the GILBERT MORGAN SMITH MEDAL. Grossman is being honored for pioneering creative and comprehensive research on algae and cyanobacteria, elucidating molecular mechanisms by which they adapt to changes in light color and to nutrient stress. The Gilbert Morgan Smith Medal and prize of $20,000 are awarded for excellence in published research on marine or freshwater algae.
ROGER W. HENDRIX of the University of Pittsburgh is awarded the NAS AWARD FOR SCIENTIFIC REVIEWING. Hendrix's reviews, overviews, and minireviews have focused research in the areas of structure, assembly, and genomics of bacteriophages and include numerous original and provocative ideas. The prize of $10,000 -- given in 2009 in the field of genetics -- acknowledges excellence in scientific reviewing within the past 10 years. The award is supported by ANNUAL REVIEWS, the Institute for Scientific Information, and THE SCIENTIST in honor of J. Murray Luck.
ALI JAVEY, assistant professor of electrical engineering and computer sciences at the University of California, Berkeley, is the recipient of the NAS AWARD FOR INITIATIVES IN RESEARCH. Javey is being recognized for seminal advances in carbon nanoelectronics, utilizing and synthesizing concepts from chemistry, physics, and engineering. The prize of $15,000 is awarded to recognize innovative young scientists and to encourage research likely to lead toward new capabilities for human benefit. The award -- established by AT&T Bell Laboratories in honor of William O. Baker and supported by Alcatel-Lucent -- is being presented in 2009 in the field of nanoscience.
TIRIN MOORE, assistant professor in the department of neurobiology at Stanford University School of Medicine, and ANDREW J. OXENHAM, assistant professor in the department of psychology at the University of Minnesota, will each receive a TROLAND RESEARCH AWARD. Moore is being honored for fundamental and insightful contributions to our understanding of the neuronal mechanisms that control directed visual attention. Oxenham is being honored for profound and rigorous contributions to our understanding of the relationship between auditory perception and its underlying physiological mechanisms. The Troland Research Awards are two research awards of $50,000 given annually to young investigators to recognize unusual achievement and to further their research within the broad spectrum of experimental psychology.
JOHN D. ROBERTS, Institute Professor of Chemistry Emeritus at the California Institute of Technology, is awarded the NAS AWARD FOR CHEMISTRY IN SERVICE TO SOCIETY. Roberts is being honored for seminal contributions in physical organic chemistry, in particular the introduction of NMR spectroscopy to the chemistry community. The award, consisting of a prize of $20,000, was established by E.I. du Pont de Nemours & Co.
KEITH W. TANTLINGER of Tantlinger Engineering is awarded the GIBBS BROTHERS MEDAL. Tantlinger is being honored for his visionary and innovative design of the cellular container ship and supporting systems that transformed the world's shipping fleet and facilitated the rapid expansion of global trade. The medal and prize of $20,000 are given for outstanding contributions in the field of naval architecture and marine engineering.
Also to be honored at the April 26 awards ceremony, which will take place during the Academy's 146th annual meeting, is NEAL F. LANE, Malcolm Gillis University Professor and senior fellow of the James A. Baker III Institute for Public Policy at Rice University, who was chosen to receive the PUBLIC WELFARE MEDAL. Lane, who served as assistant to the president for science and technology and director of the Office of Science and Technology Policy from 1998 to 2001, and as director of the National Science Foundation from 1993 to 1998, is honored for serving the scientific community in many executive and leadership roles and for his continuing efforts to advance and promote science and technology in the United States. The medal was established to recognize distinguished contributions in the application of science to the public welfare and has been presented since 1914.
The National Academy of Sciences is a private, nonprofit honorific society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Since 1863, the National Academy of Sciences has served to "investigate, examine, experiment, and report upon any subject of science or art" whenever called upon to do so by any department of the government.
[ This news release is available at NATIONAL-ACADEMIES ]
Source: Maureen O'Leary
National Academy of Sciences
воскресенье, 2 октября 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 W??thrich
$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 W??thrich 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 W??thrich
$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 W??thrich 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
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