NIGMS - National Institute of General Medical Sciences
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Director's overview

The fundamental biomedical and behavioral research supported by the National Institute of General Medical Sciences (NIGMS) canvasses a wide spectrum, ranging from experiments with organisms, cells, genes and molecules to studies of systems biology that examine the behavior of interconnected networks. Advances in each of these areas have propelled progress for the treatment, diagnosis and prevention of diseases like cancer, diabetes, infections and many others. This past year's Nobel prizes offer compelling proof that curiosity-driven basic research pays unexpected dividends.

The 2009 Nobel Prize in Physiology or Medicine went to three American scientists for their discoveries about telomeres—the "shoelace tips" that guard and protect the ends of each of our chromosomes. All long-time NIGMS grantees, these researchers were honored for their seminal work that has implications for cellular aging, cancer and other health issues. Cancer cells that divide endlessly, for example, appear to have an enhanced ability to renew their telomeres. Clinical trials are underway to test vaccines directed against cells with very active telomerase, the enzyme that makes and preserves telomeres and to test inhibitors of telomerase. Other studies are ongoing to understand the role of telomerase in certain forms of congenital aplastic anemia and other inherited diseases of the skin and the lungs that are caused by defective telomerase.

The 2009 Nobel Prize in Chemistry honored studies of a process that is vital for the health of every cell in the body: translating the DNA code into life. NIGMS funded all three of the awardees for decades as they painstakingly worked out the details of this difficult problem. Their experiments have explained—atom-by-atom—how cellular factories called ribosomes produce proteins. In recent work, these scientists have examined structures that illustrate how different antibiotics bind to ribosomes.

Solving the Structures of Life

NIGMS-funded research continues to clarify the still-not-understood language written in our genes, bringing our society ever closer to the time when personalized medicine will be routine. That means that we as individuals will know ahead of time how we are likely to react to a medicine.

A recent NIGMS-funded study found a gene variant (an altered DNA spelling) that predicts clinical outcome in women with breast cancer taking the drug tamoxifen. In addition to deepening knowledge about the natural course of disease, steady progress in the field of pharmacogenomics is leading to safer and more effective medicines. For example, this past year, researchers funded by the NIGMS-led NIH Pharmacogenetics Research Network discovered a new, gene-based method to help doctors determine a patient's optimal dose of the blood thinner warfarin. Another study reported that a gene variant carried by about a third of the population plays a major role in this group's response to a different anti-clotting medicine, clopidogrel (Plavix®). Despite its widespread use, up to a third of people do not respond to clopidogrel and as a result, experience serious cardiovascular events as a result of inadequate drug therapy.

Collectively, research results in this important area of biomedicine are prompting the Food and Drug Administration to consider changing the labeling requirements for important medicines taken by millions of Americans. Currently, genetic tests are required, recommended or mentioned for 14 drugs to treat a range of conditions including HIV/AIDS, cancer, seizures and cardiovascular disorders. Pharmacogenomics will undoubtedly become a very compelling aspect of medical practice, and along the way it will likely play a role in health care reform.

Dovetailing with this progress in genetics and genomics is an increased understanding of proteins. Researchers have made important gains in understanding how a protein's three-dimensional shape determines its function—or lack of function—in disease. Over the last two years, NIGMS grantees overcame monumental technical hurdles in solving the structures of human G protein-coupled receptors This group of proteins is quite challenging to study in detail but is extremely important from a medical standpoint since these proteins control critical bodily functions, several of our senses, and the action of about half of today's medicines.

The Many Faces of Science

A recent report1 issued by the National Research Council of the National Academy of Sciences calls for a broad acceptance of the necessity of recognizing and introducing a "new biology" in modern areas of science including biomedicine. The report details an approach to research in which physicists, chemists, computer scientists, engineers, mathematicians and other researchers are integrated into the field of biology to create the type of research community that can tackle society's big problems. I am pleased to say that NIGMS has been pursuing interdisciplinary solutions to biomedical problems for many years.

A cornerstone of the NIGMS mission is preparing for the future by supporting the research training of the next generation of biomedical and behavioral researchers who will form those teams. We are keenly attuned to challenges in this area, in particular to an imbalance in representation of women and minorities in science careers. As biomedicine continues to evolve, it is essential that we periodically go back to basics to define—clearly and functionally—the fundamental goals of research training. NIGMS has recently led an NIH-wide effort to support social science research addressing factors that help foster women's careers in science. Furthermore, the Institute is embarking on a strategic plan for research training that will garner evidence and input from the scientific community and prioritize the steps necessary to create and sustain a healthy and productive research training environment that mirrors the composition of the United States. We envision that the results of this process will be far-reaching and will help inform NIH-wide policy in this area.

1. A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution. Accessed September 21, 2009

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