Pamela Silver

Pamela Silver an American cell and systems biologist and a bioengineer. She holds the Elliot T. and Onie H. Adams Professorship of Biochemistry and Systems Biology at Harvard Medical School in the Department of Systems Biology. Silver is one of the founding Core Faculty Members of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

She is one of the founders of the emerging field of Synthetic Biology. She has made contributions to other disciplines including cell and nuclear biology, systems biology, RNA biology, cancer therapeutics, international policy research, and graduate education. Silver was the first Director of the Harvard University Graduate Program in Systems Biology.

Education and Research

Silver grew up in Atherton, CA where she attended Laurel and Encinal Elementary Schools. During this time, she was a winner of the IBM Math Competition and received special recognition for her early aptitude in science. She attended Menlo Atherton High School and graduated from Castilleja School in Palo Alto. She received her B.A. in Chemistry from the University of California, Santa Cruz and her PhD in Biological Chemistry from the University of California, Los Angeles, where she worked on membrane protein assembly with William Wickner. She did her postdoctoral training with Mark Ptashne at Harvard University where she discovered one of the first nuclear localization sequences.

While in the Ptashne lab, Silver discovered the first nuclear localization sequence (NLS) in the yeast GAL4 protein. She continued to study the mechanism of nuclear localization in her own lab as an Assistant Professor at Princeton University. During this time, she characterized the receptor for NLSs and discovered the first eukaryotic DnaJ chaperone.

Silver continued in the area of Cell Biology upon moving to the Dana Farber Cancer Institute to hold the Claudia Adams Barr Investigatorship and to become Associate Professor of Biological Chemistry and Molecular Pharmacology eat Harvard Medical School and Dana-Farber. During this time, she was among the first to follow GFP-tagged proteins in living cells. In addition, she initiated early studies in systems biology to examine interactions within the nucleus on a whole genome scale. Together with Bill Sellers, she discovered molecules that block nuclear export and formed the basis for a publicly traded company Karyopharm Therapeutics. She was promoted in 1997 to Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Dana-Farber.

In 2004, Silver moved to the newly formed Department of Systems Biology at Harvard Medical School as a Professor. Around this time, she engaged with the Synthetic Biology Working Group at MIT and made the decision to move her research group into Synthetic Biology. Since then, she has developed numerous genetic circuits in all types of cells, engineered carbon fixation, and developed new therapeutic proteins and biofuel precursors. She was the first to observe the motion of the carbon fixing organelles in photosynthetic bacteria. During this time, she has also been the Director of an ARPA-E (DOE) project on electrofuels.

Contributions to Science

Synthetic Biology

Silver seeks to re-program both eukaryotic and prokaryotic cells. Applying synthetic biology to mammalian cells is a new frontier in the field and has a vast number of potential implications for human, animal and plant health as well as environmental sustainability. Some of Silver’s work in this area includes the engineering of: mammalian cells to remember and report past exposures to drugs and radiation, robust computational circuits in embryonic stem cells and bacteria, and synthetic switches to moderate gene silencing with the integration of novel therapeutic proteins.

Re-programming the gut microbiota

Silver has engineered natural gut bacteria that can pass through an animal’s digestive tract and report whether an animal has been exposed to a drug. Given that gut microbiota plays a key role in maintaining the health of all mammals and is a potential site for diagnostic and therapeutic intervention, Silver’s work sets the stage for the development of novel therapies for use in both humans and in the livestock industry.

Living foundries

Silver has developed ways to enhance the production of important molecules from metabolically-engineered bacteria, reflecting a change in biomanufacturing approaches towards a cleaner commodity industry and less reliance on petroleum-based products.

Carbon fixation and cell consortia

Silver has characterized the carboxysome – the major carbon-fixing structure in cyanobacteria – to enhance photosynthetic efficiency and carbon fixation. She has also engineered cyanobacteria to more efficiently cycle carbon into high-value commodities and has shown that these bacteria can form sustainable consortia.

“Bionic Leaf”

File:Bionic leaf.png

The bionic leaf is a system for converting solar energy into liquid fuel developed by the labs of Daniel Nocera and Pamela Silver at Harvard.

Silver collaborated with Daniel Nocera at Harvard University to develop a device that converts solar energy into fuel through a hybrid water-splitting catalyst system that leverages metabolically-engineered bacteria. Called the “Bionic Leaf”, the device is as efficient at producing hydrogen as natural plants and can be easily modified to reach higher efficiency of conversion and storage of solar energy.

Gene regulation

Silver discovered a strong correlation between nuclear transport and gene regulation – she identified the first arginine methyltransferase, which plays a role in chromatin function and is important to the movement of RNA binding proteins between the nucleus and cytoplasm of cells. She also discovered previously unknown variations among ribosomes that led her to propose a unique specificity for the matching between ribosomes and the subsequent translation of mRNAs. Silver’s finding has several implications towards our understanding of how gene regulation impacts disease development, such as cancer.

RNA processing and transport

Silver has used a novel genetic screen in yeast to study nuclear transport, which led to her discovery of several key factors including RNA binding proteins that also control other aspects of mRNA processing. She was among one of the first to show the kinetics of these RNA transport factors moving between the nucleus and cytoplasm of cells, using green fluorescent protein (GFP) imaging. This led Silver to propose a close interplay between RNA transport factors that has impact on mRNA splicing and transport and the subsequent development of some genetic diseases.

Awards

Silver has been the recipient of an NSF Presidential Young Investigator Award, a Basil O’Connor Research Scholar of the March of Dimes, an Established Investigator of the American Heart Association, the NIH Directors Lecture, and NIH MERIT award, Innovation award at BIO, a Fellow of the Radcliffe Institute for Advanced Study, the Elliot T. and Onie H. Adams Professorship at Harvard Medical School and named the Top 20 Global Synthetic Biology Influencers. She sits on numerous advisory boards and has presented to members of the US Congress.

Roles in Education

Silver was awarded the BBS Mentoring Award for Graduate Education at Harvard Medical School. She is also one of the founders of the International Genetically Engineered Machines competition (iGEM) and currently sits of the Board of iGEM.org. Silver founded and was the first Director of the Harvard University Graduate Program in Systems Biology. Silver is a strong advocate for women in science.

Other Activities

Silver has completed three Boston Marathons. She is an avid sailor and co-owns a Viper 640 that she races in Marblehead, MA.

External links

• The Silver Lab
• Silver profile page, Wyss Institute
• Department of Systems Biology at Harvard
• Systems Biology PhD Program
• iGEM