Pamela A. Silver

Department of Systems Biology
Harvard Medical School
Warren Alpert Building, Room 420
200 Longwood Avenue
Boston, MA 02115

tel: (617) 432-6401; FAX: (617) 432-5012
email: pamela_silver@hms.harvard.edu
web: http://openwetware.org/wiki/Silver_Lab

Research Interests:

My group focuses on systems and synthetic biology. We are trying to understand how sets of molecules and cells function together to generate spatial and temporal organization. At the same time, we are developing design principles to create complex biological systems. Some of the current research areas are summarized below.

Designing Biological Systems
Our goal is to both enhance our understanding of natural biological design, and to develop tools and concepts for designing artificial organisms. In the long term, we hope to develop principles for building novel cells that act as sensors, memory devices, bio-computers, and energy producers, and to build novel subsystems such as proteins with designed properties. Current projects use mammalian cells, simple eukaryotes and prokaryotes to create artificial proteins with therapeutic value, a cellular oscillator that could lead to pulsatile drug or hormone delivery, sensors of spatial organization, and manipulation/creation of metabolic pathways to produce economical energy sources. These experiments use a combination of theoretical and experimental approaches that are well suited to students with a background in biology, engineering, physics or any allied field.

Pathways in Disease
Many signaling pathways employ spatial organization as a key part of their response to environmental stimuli. 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. Currently, we are building on these findings to gain a more quantitative picture of how tumor cells respond to certain drugs. We employ a combination of high-resolution microscopy, modeling and cell-based screens.

Genome Organization
Our studies of nuclear organization concern the spatial and temporal relationships between genes, RNAs and other nuclear components and their functional significance. It has become increasingly clear that the organization of genes within the nucleus plays an important role in cell identity and epigenetics. Current interests in the lab include studying the dynamic nature of genomes under different growth states, in different cell types and in response to drugs in development as anti-cancer therapeutics. We also study the dynamics of post-transcriptional regulation and its relationship to the organization of the genome in response to drugs and diseases. Results from these experiments provide a basis for some of the synthetic biological designs.

Selected Publications:

Savage, D.F., Way, J., and Silver, P.A. (2008). Defossilling fuel: how synthetic biology can transform biofuel production. ACS Chem. Biol. 3: 13-6.

Drubin, D., Way, J., and Silver, P.A. (2007). Designing Biological Systems. Genes & Devel. 21(3): 242-54.

Komili, S., Farny, N.G., Roth, F.P., and Silver, P.A. (2007). Functional specificity among ribosomal proteins regulates gene expression. Cell 131: 557-71.

Ajo-Franklin, CM, Drubin, DA, Eskin, J., Gee, E., Landgraf, D., Philips, I. and Silver, PA. (2007). Rational design of memory in eukaryotic cells. Genes & Devel. 21(18): 2271-6.

Page created and maintained by Xaq Pitkow