Pamela Silver
The Silver Lab works at the interface between systems and synthetic biology to design and build biological systems in both mammalian and prokaryotic cells. Some current projects include analysis of cells that remember past events, cell-based computation and therapeutics, and metabolic engineering for bio-energy and sustainability.
Harvard Medical School, Department of Systems Biology
Alpert Building, Room 420
200 Longwood Ave.
Boston, MA 02115
Tel: 617-432-6401
Email: pam@hms.harvard.edu
Website:
http://silver.med.harvard.edu/ or http://openwetware.org/wiki/Silver_Lab
Lab Size: Over 20
Summary
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.
Publications
Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model. Hsu BB, Gibson TE, Yeliseyev V, Liu Q, Lyon L, Bry L, Silver PA, Gerber GK. 2019. Cell Host Microbe. Link
Prokaryotic nanocompartments form synthetic organelles in a eukaryote. Lau YH, Giessen TW, Altenburg WJ, Silver PA. Nat Commun. 2018 Apr 3;9(1):1311. doi: 10.1038/s41467-018-03768-x. PMID: 29615617. Link
Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Riglar DT, Giessen TW, Baym M, Kerns SJ, Niederhuber MJ, Bronson RT, Kotula JW, Gerber GK, Way JC, Silver PA. Nat Biotechnol. Link
A targeted erythropoietin that selectively stimulates red blood cell expansion in vivo. Burrill DR, Vernet A, Collins JJ, Silver PA, Way JC. Proceedings of the National Academy of Sciences USA. PMID: 27114509
Water splitting-biosynthetic system with CO₂ reduction efficiencies exceeding photosynthesis. Liu C, Colón BC, Ziesack M, Silver PA, Nocera DG. Science. PMID: 27257255