For nearly 50 years, the National Institute of General Medical Sciences (NIGMS) has been a powerful engine of discovery. As NIH's "basic research institute," NIGMS has built a strong foundation of knowledge about health and disease. The NIGMS mission is appropriately broad to enable discovery in many areas of study--ranging from the properties and behavior of molecules and cells to the spread of disease within entire communities. NIGMS is proud to have supported the research of numerous Nobel Prize winners in Physiology or Medicine. This past year was no different, with an NIGMS-supported scientist sharing a Nobel for his discovery of a groundbreaking chemistry method that is used routinely in the medical, electronic, and agricultural industries.
Tools for Faster Discovery
The Institute's investment in enabling technologies continues to be robust. One of NIGMS' signature efforts for the support of rapid, high-volume technology is its Protein Structure Initiative (PSI). In July 2010, the Institute launched PSI:Biology. This new program supports research partnerships between groups of biologists and high-throughput structure determination centers to solve medically important problems.
In 2010, NIGMS also enhanced its support of systems biology, by adding two new National Centers for Systems Biology. As with the 10 other currently funded centers, the new centers will integrate approaches from engineering, genomics, systems biology, and synthetic biology to identify mechanisms and structural features involved in common cellular behaviors, including the response to disease-causing microorganisms, poisons, and metabolic imbalances.
Basic Science for Better Health Care
The basis of sound health care is solid scientific evidence for making treatment-related decisions. A long-standing interest area within the NIGMS research portfolio is pharmacogenomics, which seeks to understand how medication response varies among individuals because of inherited differences. NIGMS leads the trans-NIH Pharmacogenomics Research Network (PGRN), a nationwide collaboration of scientists (see page 18 for Program Portrait). Over the next five years, this effort will expand our understanding of medication response through the use of cutting-edge DNA sequencing methods and statistical analyses, as well as pilot studies to learn about medication response from de-identified medical records in health care systems.
In a compelling advance from 2010, scientists at Stanford and Harvard teamed up to use a healthy person's complete genome sequence to generate a first-of-its-kind personalized risk report. The researchers accomplished this feat by comparing the individual's genetic signatures against several databases of disease-related gene variants, and then also factored in the patient's medical and family history and statistical disease risks. This tailored "risk report" is a potential model for truly personalized medicine.
Feeding the Therapeutic Pipeline
NIGMS-funded discoveries continue to pave the way toward new ways to treat illness and injury. This past year researchers discovered important new information about how wounds heal in the skin. They learned that skin cells that travel to a severe wound go into a cellular "holding pattern" called senescence and instead of dividing, the cells secrete substances that help remodel the surrounding skin, effectively preventing scar formation. This new knowledge may inform therapies to slow or prevent the formation of scar tissue in critical organs--such as the liver after hepatitis infection. Scar tissue in organs can impair their function.
Another 2010 example of NIGMS-funded basic research directly relevant to disease is a large, gene-scanning project that looked for potential, non-inherited interactions between the environment and our genes. In this research, an NIGMS-funded physician scientist (a combined pediatrician/computer modeler) examined hundreds of environmental factors for their potential role in causing type 2 diabetes. The search turned up 226 factors that appear to contribute to the onset of disease. These included known toxins like polychlorinated biphenyls and also new suspects such as a pesticide product and a common form of vitamin E. The results offer important new clues for diabetes researchers to follow.
The Wide Reach of Basic Research
Computational modeling is a powerful tool for understanding disease outbreaks and predicting the implications of specific public health measures. The NIGMS-funded Models of Infectious Disease Agent Study (MIDAS) program develops computational models for conducting virtual experiments to test how emerging pathogens might spread in the presence and absence of interventions. Using data from real populations and geographical locations, interdisciplinary MIDAS researcher teams have created computer simulations that help predict a range of public health outcomes for epidemics of flu and other diseases in the United States, Mexico, and India.
NIGMS-supported research related to HIV/AIDS also has significant global health relevance. In 2010, scientists solved the three-dimensional structure of a molecule involved in HIV infection and in many forms of cancer. The research shed light on CXCR4, a molecule that acts as a cellular gateway for HIV and harmful substances. While scientists have known about CXCR4 for 15 years, until now they have lacked detailed information about how it functions. Knowing the structure has helped scientists understand the molecular properties and features of this previously enigmatic molecule.
The Future of Discovery
NIGMS has a long-standing commitment to fostering a highly capable biomedical and behavioral research workforce. Science and the conduct of research continue to evolve, though, as do workforce needs. For this reason, this past year, NIGMS completed an intensive process to develop a strategic plan for future research training and career development. Through a series of regional meetings across the country, the Institute gathered information and data, as well as input from the scientific community. This enabled us to prioritize the steps necessary to create and sustain a healthy and productive research training environment that mirrors the composition of America. A key theme in the plan, released in early 2011, is the importance of putting the needs of trainees first--by focusing on mentoring, career guidance, and diversity.