Professor of Systems Biology
Harvard Medical School, Department of Systems Biology
Alpert Building, Room 420
200 Longwood Ave.
Boston, MA 02115
We seek to both enhance our understanding of natural biological design, and to develop tools and concepts for designing cells, tissues and organisms. In the long term, we hope to develop principles for building novel cells that act as sensors, memory devices, bio-computers, producers of high value commodities and energy from the sun, and to build novel subsystems such as proteins with designed properties for therapeutic use. Current projects use mammalian cells, simple eukaryotes and prokaryotes. Understanding how to program cells in a rational way will have value, for example, in stem cell design, drug therapy and the environment. These experiments use a combination of theoretical and experimental approaches that are well suited to students with a background in biology, engineering, or any allied field.
We also take advantage of the spatial organization of cells to further understand key disease pathways. For example, the movement of key proteins in and out of the nucleus is often one of the downstream steps in signal response. We have taken advantage of this spatial organization to screen for small molecules and genes that affect signaling pathways and therapeutic targets. We employ a combination of high-resolution microscopy, modeling and cell-based screens. We also study the dynamics of post-transcriptional regulation in response to drugs and diseases. Results from these experiments provide a basis for some of the synthetic biological designs.
Burrill DR, Inniss MC, Boyle PM, Silver PA. (2012) Synthetic memory circuits for tracking cell fate. Genes & Dev. 26(13):1486-97. PMCID: PMC3403016.
Burrill DR, Boyle PM, Silver P. (2011) A new approach to an old problem: Synthetic biology tools for human disease & metabolism. Cold Spring Harbor 76th Symposium on Quantitative Biology. Dec 14 76:145-54.
Delebecque CJ, Lindner AB, Silver PA, Aldaye FA. (2011) Organization of Intracellular Reactions with Rationally Designed RNA Assemblies. Science. 333(6041):470-4. PMID: 21700839.
Smolke, C.D., and Silver, P.A. (2011). Informing biological design by integration of systems and synthetic biology. Cell. 255(6). 855-9. PMID: 21414477.
Savage DF, Afonso B, Chen AH, Silver PA. (2010). Spatially ordered dynamics of the bacterial carbon fixation machinery. Science. 327(5970):1258-61. PMID: 20203050.