3/3/2003 8:00 AM
3/3/2003 8:00 PM
The mission of the National Institute of General Medical Sciences (NIGMS) is to support basic biomedical research that is not targeted to specific diseases. NIGMS funds studies on genes, proteins, and cells, as well as on fundamental processes like communication within and between cells, how our bodies use energy, and how we respond to medicines. The results of this research increase our understanding of life and lay the foundation for advances in disease diagnosis, treatment, and prevention. NIGMS attempts to ensure the vitality and continued productivity of basic biomedical research, while producing the next generation of scientific breakthroughs and training the next generation of scientists.
To support high-quality basic research that will lead to the medical and industrial advances of the future and that will provide the basis for further progress in understanding the fundamental behavior of biological systems. The primary approach is through the support of peer-reviewed, investigator-initiated, individual research grants.
To provide opportunities for long-term and/or high-risk research , when the possible impact of a successful outcome warrants the investment. This requires some measure of stability for the individual investigator, consistent with the need to maintain high quality. It also requires the stimulation and encouragement of emerging areas of science that do not yet have the broad recognition needed to ensure their acceptance.
To establish programs that will result in a cadre of highly qualified researchers. This requires developing flexible training mechanisms that reflect the rapidly changing needs of science, as well as providing cross-disciplinary training opportunities.
The vast majority of NIGMS support goes to investigator-initiated individual research grants. But NIGMS also produces a number of initiatives or policy statements that are intended to reflect aspects of science that require particular attention or stimulation. These are developed through the following procedures:
The National Advisory General Medical Sciences (NAGMS) Council generates recommendations for new initiatives.
In addition, NIGMS regularly evaluates the program areas it supports to determine whether any of these research fields are undergoing significant growth or shrinkage. Every few years, NIGMS holds an Institute-wide retreat to discuss issues of management and programmatic balance.
The special initiatives featured below reflect only a sampling of NIGMS' efforts to facilitate new directions in research. A complete listing of NIGMS programs, policies, and initiatives can be found on the NIGMS Web site (http://www.nigms.nih.gov).
Pharmacogenetics is the science of how variations in people's genes influence how they respond differently to medicines, including antidepressants, cancer chemotherapy, and cardiovascular and asthma drugs. NIGMS is leading a trans-NIH effort in which a network of investigators will store data in an electronic library called PharmGKB that is freely accessible to the scientific community. In April 2000, NIH made the first nine awards for the Pharmacogenetics Research Network. In September 2001, NIGMS extended the network by making four additional awards. The long-term goal of this research is to help doctors prescribe the type and dose of medicines based on each patient's unique genetic make-up. This will make medicines safer and more effective for everyone. The Pharmacogenetics Research Network is described at pharmacogenetics/.
Protein Structure Initiative
This initiative, often referred to as "structural genomics," is designed to reveal the three-dimensional structure of all proteins in nature and to advance the techniques required for solving protein structures.Knowing the shapes of proteins helps scientists to better understand how proteins function normally and how faulty protein structures can cause disease. Through its large-scale protein structure initiative (PSI), NIGMS is supporting groups of scientists to solve the detailed structures of selected proteins.These structures will then be used to predict the structures of other proteins based on their gene sequences.In September 2000, NIGMS provided the first year of funding for seven pilot research centers, each of which will be funded for 5 years. In September 2001, it awarded grants to two more centers.By around 2010, NIGMS hopes to have 10,000 structures in a database that will be freely available to the scientific community. The Institute also holds workshops to address needs and obstacles in structural genomics. The Protein Structure Initiative is described at
Collaborative Research ("Glue Grants")
Recognizing the increasing need for collaborative research, NIGMS created an initiative to "glue" together large groups of scientists pursuing some of the biggest unsolved problems in basic biomedical research today. The purpose is to support the formation of large research teams drawn from different institutions to tackle problems that are not likely to be solved by individual research laboratories. In September 2000, NIGMS made the first "glue grant" to the Alliance for Cellular Signaling (see
http://www.signaling-gateway.org ), a consortium of basic scientists that is studying communication in two different cell types:the cardiac myocyte (heart cell), and the B lymphocyte (immune cell). In September and October 2001, NIGMS funded three more glue grants.The Consortium for Functional Glycomics focuses on the role that carbohydrates (sugar molecules) play in cellular communication (see
http://web.mit.edu/glycomics/consortium/ ).The Cell Migration Consortium (see
http://www.cellmigration.org/ ) probes the molecular mechanisms of how cells move, which are essential for processes ranging from embryonic development and the body's response to infections, to the spread of cancer.Inflammation and the Host Response (see
http://www.gluegrant.org/ ) investigates how the human immune system reacts to serious burns and traumatic injuries.A better understanding of this process will lead to clear clinical benefits such as increasing survival rates and quality of life for patients and reducing the length of hospital stays and the cost of treating serious injuries.
Complex Biological Systems
NIGMS has created a set of initiatives to promote quantitative, interdisciplinary approaches to studying complex biological systems. For the past several decades, biomedical research has largely focused on identifying and characterizing individual molecules.Now, with an avalanche of biological data arising from gene sequencing projects and the availability of other new technologies, biologists are eager to explore the intertwined networks that underlie complex processes such as cell behavior, embryonic development, and the progression of multifaceted disorders like heart disease. Because such workrelies on computational modeling, this effort seeks to enlist the expertise of mathematicians, physicists, engineers, and computer scientists. Descriptions of efforts to recruit quantitative scientists, opportunities for training, and areas of special research interest in this area are available at http://www.nigms.nih.gov/funding/pages/complex_systems.aspx.
Two of these initiatives are described below.
Joint NSF/NIGMS Initiative to Support Research in Mathematical Biology (https://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5300) Together with the National Science Foundation's Division of Mathematical Sciences, NIGMS is sponsoring an effort to develop and apply mathematical techniques to a wide range of biomedical problems, including cell behavior, molecular structure and dynamics, the physiological effects of various drugs, and human responses to burns and other traumatic injury.
Centers of Excellence in Complex Biomedical Systems Research (http://grants1.nih.gov/grants/guide/rfa-files/RFA-GM-03-002.html) These centers will encourage interdisciplinary research, train undergraduates in quantitative biology, and recruit and train in biology investigators who have quantitative backgrounds.
Due to its strong emphasis on computational modeling of biological systems, NIGMS was chosen to oversee NIH's Biomedical Information Science and Technology Initiative (BISTI). The goal of this initiative is to make optimal use of computer science and technology to address problems in biology and medicine. The BISTI Consortium is composed of senior-level representatives from various components of NIH and from other Federal agencies concerned with computing in the life sciences. More information about BISTI, including research and training opportunities, can be found on the NIH Bioinformatics Web Site (http://www.bisti.nih.gov/).
Evolution of Infectious Diseases
Infectious diseases change over time as a result of intricate relationships between microorganisms and their hosts. Understanding the evolution and population dynamics of infectivity, host response, virulence, transmission, and drug resistance is an important step in the control of infectious diseases.In 1998, NIGMS began an initiative to encourage multidisciplinary groups of scientists to develop ways to predict events such as when and where new infectious diseases will emerge, under which conditions drug resistance will arise, and what will happen in response to therapeutic interventions. ?The effort takes advantage of the immense amount of information available on microbes and harnesses many exciting new computational and mathematical approaches.NIGMS has funded 27 grants on a variety of infectious disease systems. This NIGMS initiative is described at
In 2003, NIGMS issued a related initiative called Models of Infectious Disease Agent Study (MIDAS).MIDAS will consist of a centralized database and a network of multidisciplinary scientists using computational and mathematical models to improve the detection, control, and prevention of emerging infectious diseases, including those relevant to biodefense. More information about MIDAS is available at
Human embryonic stem cells offer a unique model system in which to ask basic questions about how cells divide and differentiate and to screen potential new drugs. Research on these cells promises to shed light on--and possibly yield new ways to treat--many diseases. Scientists hope that stem cells may one day provide a rich source of replacement cells and tissues to treat myriad conditions including Parkinson's disease, diabetes, spinal cord injury, heart disease, arthritis, and vision and hearing loss.Since federal funds for studying human embryonic stem cells have only been available since August 2001, this field is still in its infancy. NIGMS has two initiatives to encourage researchers to use these cells to explore fundamental biological processes. Information about these initiatives, along with other information about human embryonic stem cells, are available at
New and Enhanced Research Tools
NIGMS has always recognized the importance of providing its grantee researchers with tools necessary to conduct their work. Depending on whether the scientists focus on molecular and structural biology, genetics, computational biology, or bioinformatics, they require resources that can include high-resolution NMR or synchrotron facilities, mass spectrometers, high-speed computers, and DNA arrays. Examples of how NIGMS supports the development of new research tools are listed below.
The number of solved protein structures has increased dramatically in recent years, due in large part to the availability of powerful X rays from synchrotrons. ?The nation's synchrotron facilities are also critical to the NIGMS Protein Structure Initiative (see
above ). To advance the field of synchrotron-based X-ray crystallography and to reduce the waiting time for researchers seeking access to synchrotrons, NIGMS announced the initiatives below.
Support of Five U.S. Synchrotrons
NIGMS is supporting major instrumentation enhancements and the hiring of additional staff at four U.S. synchrotrons (Stanford Linear Accelerator Center in Menlo Park, CA; Lawrence Berkeley National Laboratory's Advanced Light Source in Berkeley, CA; Brookhaven National Laboratory's National Synchrotron Light Source in Upton, NY; and the Cornell High Energy Synchrotron Source in Ithaca, NY). Together with the National Science Foundation, it is also supporting development of a beamline at Louisiana State University's Center for Advanced Microstructures and Devices in Baton Rouge, LA.
Three New Beamlines at Argonne's Synchrotron
NIGMS, in partnership with the National Cancer Institute, is planning to develop and operate three new beamlines at the Advanced Photon Source, the newest and most advanced U.S. synchrotron, which is located at Argonne National Laboratory in Argonne, IL.The new beamlines should be available for use in 2005.
Another technique used to determine three-dimensional structures is nuclear magnetic resonance (NMR) spectroscopy. A breakthrough in technology has allowed the construction of a new generation of more powerful NMR spectrometers. These new instruments contain extremely strong magnets (900 MHz) and provide much clearer pictures of many different types of molecules than do current machines. Targets for the new spectrometers include large proteins, flexible proteins, and carbohydrates bound to lipids or proteins.All of these molecules are critical for many biological functions, but have been difficult to study until now. In July 2002, NIGMS committed to supporting the construction of four new 900 MHz NMR magnets.In 2003 the Institute expects to provide funds for up to two more.More information about this initiative is available at
High-Resolution Electron Microscopy
Many cellular structures are too large to be studied with X-ray crystallography or NMR spectroscopy and cannot be viewed in adequate detail by light microscopy. Such structures can be examined using high-resolution electron microscopy (EM), but current high-resolution EM techniques are not advanced enough to be used for routine, high-throughput studies. NIGMS supports the development of improved instrumentation (see
http://grants.nih.gov/grants/guide/pa-files/PA-00-083.html ) and, together with two other NIH components, supports technology development in this area (see
Single Molecule Studies
Scientists studying the behavior of biological molecules often rely on analyzing the average behavior of many of these molecules. To do this, they often isolate the molecules from their natural environment and may even freeze, crystallize, or otherwise preserve the molecules in a single position. Several new techniques allow researchers to examine and manipulate individual molecules and to examine the behavior of these molecules under natural conditions, in living cells and in real time. Once fully developed, these techniques should enable scientists to examine a variety of biological processes , such as the opening and closing of ion channels, the folding of protein and RNA molecules, the movement of molecular machines, variations in the efficiency of individual enzymes, and the expression of genes in specific tissues or at certain developmental stages. This initiative is described at
In recent years, chemists have learned to create collections of different molecules made from a few chemical building blocks. These collections are known as combinatorial chemistry libraries. Scientists can rapidly screen through these libraries to discover potential new drugs and molecules that can be used to study biological processes. ??The promise and utility of these libraries is limited by current methods. In October 2002, NIGMS funded two collaborative research "Centers of Excellence" in which scientists with diverse expertise work together to develop new ways to create high-quality combinatorial chemical libraries. The Institute expects to support up to four more centers over the next 2 years.
To conduct large-scale genetic research or other studies that would be difficult or impossible to conduct in humans, scientists often use simpler organisms that have many of the same (or similar) genes as humans. Each such "model organism" has its own strengths and scientific uses. NIGMS supports research and technology that makes these models more useful. Examples of such support are below.
These inexpensive, fast-growing fish are useful for studying basic biological processes, such as gene regulation, chromosome organization, cell growth and differentiation, behavior, and the genetics of complex traits and diseases/disorders. Zebrafish are capable of a number of genetic tricks, such as producing offspring that contain genes only from one parent, offering scientists a unique opportunity to use genetic strategies to understand basic biologicalproblems. In addition, zebrafish eggs are transparent, making them particularly valuable for studies of embryonic development. These initiatives are described at at
Generic Model Organism Database
Several major model organism databases are available to the scientific community.NIGMS and the National Human Genome Research Institute are co-sponsoring an initiative to develop database components, or modules, designed to facilitate data analysis of genetic and genomic information in these databases. The modules will process data in formats that are compatible with existing databases and will thus allow data sharing between these databases. In addition, the modules can be put together to form a "generic" model organism database, which will serve as a template for future model organism databases. The effort is described at
Programs for Underrepresented Minorities
NIGMS is committed to supporting research and research training programs that increase the number of underrepresented minority biomedical/behavioral scientists in the United States. The Institute has a Division of Minority Opportunities in Research (MORE) that contains two branches and several special initiatives designed to increase the number of underrepresented minority biomedical or behavioral scientists. The Minority Access to Research Careers Branch supports research training at the undergraduate, graduate, and faculty levels. The Minority Biomedical Research Support Branch funds faculty-initiated research projects and/or student development grants at educational institutions with significant underrepresented minority student enrollments. These grants help strengthen the institutions' biomedical research capabilities and develop the research competitiveness of the participating faculty. Descriptions of MORE initiatives are available.
Programs to Reduce Health Disparities
A number of diseases and health conditions disproportionately affect minority and medically underserved communities in the United States. NIGMS supports a companion program to the Pharmacogenetics Research Network (PGRN), which is designed to reduce health disparities.These Pharmacogenetics Research Network Supplements for Health Disparities (http://grants.nih.gov/grants/guide/notice-files/NOT-GM-01-004.html) were designed to extend ongoing PGRN research programs to include studies of identified population groups. The supplements support studies that link differences in responses to medicines with genes that are more common in certain populations. Such knowledge could contribute to a reduction in health disparities by improving doctors' abilities to identify and treat individuals who have these genes.
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