2010 Stetten Lecture -- Measuring and Modeling Life-Death Decisions in Single Cells

Masur Auditorium
Clinical Center (Building 10)
National Institutes of Health
Bethesda, Maryland

Start Date: 10/20/2010 3:00 PM

End Date: 10/20/2010 4:00 PM

2010 Stetten Lecture poster - Measuring and Modeling Life-Death Decisions in Single Cells

Videocast - Peter SorgerStetten Lecture videocast

Speaker: Peter Sorger, Ph.D.
Professor of Systems Biology
Harvard Medical School

Biographical Sketch

One of the fundamental mysteries of biology is how cells with the same genetic blueprint can end up behaving so differently. This theme underlies the development of a fertilized egg into the many cell types of a multicellular organism. It also applies in fully formed organisms, where cells that appear the same can vary enormously in how they respond to their environment. In cancer, for example, subtle shifts in signaling proteins cause dramatic changes in cell fate, and genetically identical cancer cells may react very differently to drug treatments.

Peter Sorger uses a systems approach to address the apparent paradox of how cells can respond so variably when life seems to depend on the precise control of biochemical processes. Since randomness plays a role, he argues that the traditional way biologists describe molecular interactions, with simple pictorial models, should yield to more nuanced mathematical representations that assign probabilities to biochemical events. In addition, he points out, as the complexity and number of interactions grow, it becomes less and less possible to intuit the phenotypic consequences of changes in protein abundance or activity.

Sorger’s research combines experimental and computational methods to study complex dynamics in living systems and variability in signal transduction among cells. As a model system, he and his research group have studied cell responses to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an investigational cancer drug. When human cells are treated with TRAIL, some die within 40 minutes, others die after 12 hours, and still others survive indefinitely. Sorger’s group has explored the interaction of genetic or epigenetic variations, stochastic fluctuations in biochemical processes and transient differences in cell states. He has found that stochastic fluctuation plays a major role in determining variability among otherwise identical cells. In these and other studies, Sorger’s aim is to model and measure the pathways that promote either survival or death in mammalian cells and to better understand the factors that tilt the life-death balance.

Sorger has been a professor of systems biology at Harvard Medical School since 2006. He has a joint appointment at the Massachusetts Institute of Technology, where he is a professor of biological engineering and has been a faculty member since 1994. In addition, Sorger is the director of the Center for Cell Decision Processes at MIT, an NIH Center of Excellence in Systems Biology. He received an A.B. in biochemistry from Harvard University in 1984 and a Ph.D. in biochemistry from Trinity College in Cambridge, England, in 1987. Sorger conducted postdoctoral research in cell and molecular biology with Harold Varmus and Andrew Murray at the University of California, San Francisco.

Sorger is a great believer in collaboration. He received one of the first NIH dual-principal investigator R01 grants. He helped found MIT’s Computational and Systems Biology Initiative (CSBi) and the Council for Systems Biology in Boston (CSB2). Both organizations foster links among researchers from varied backgrounds to promote studies in systems and computational biology.

NIGMS has supported Sorger’s research since 1994.