History and Philosophy

The Silver group has followed many different scientific paths over the years so I thought I would provide a little history and perspective here. Most of our success can be attributed to the numerous students and fellows who have travelled through the lab over the years.

The group began around my original discovery of one of the first nuclear localization signals – short peptides that target proteins to the nucleus. Following on this, the focus was on the organization of the nucleus and movement of molecules between the cytoplasm and the nucleus. In the course of this work, we developed and confirmed some of the models of nuclear transport, developed a systems-wide approach to the problem and people extended this work as they departed to establish their own groups. The lab was continuously funded by the NIH including with a MERIT award and was located for many years in the Dana Farber Cancer Institute and the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. We made a number of contributions to development of anti-cancer therapies – including a small molecule screen, which resulted in a novel cancer therapeutic now FDA approved by Karyopharm Therapeutics as well as pioneering some of the first uses of GFP to track molecules within cells.

Some years ago, I had the good fortune to meet a group of computer scientists and bio-engineers who formed the Synthetic Biology Working Group at MIT. My group became increasingly engaged in developing the fields of Systems and Synthetic Biology and we are now recognized as leaders in efforts to engineer biological systems to perform useful tasks. As a result of these efforts, I became one of the founding members of the Department of Systems Biology at Harvard Medical School. This was a good fit because Synthetic Biology seeks to provide a computational framework to make the engineering of biological systems faster and more predictable. I participated in formulating the first definitive report on Synthetic Biology for the US government, which helped set the international agenda for the field.

We have enjoyed a number of successes including the rational engineering of genetic circuits in both eukaryotes and prokaryotes, metabolic engineering to re-route carbon metabolism and the application of modularity in cell engineering and the design of organisms to report on states within animals. The development of the Bionic Leaf and natural gut bacteria that sense prior drug exposure to animals illustrate many of our approaches.

Our group has a very informal atmosphere. We encourage people to work on interesting, unsolved problems that might have broad implications. We also encourage collaborations and forays into completely new areas. For example, we are working with Neri Oxman at MIT on photosynthetic wearables and Dan Nocera on the Bionic Leaf. I also believe in the empowerment of young researchers as they are the future of science. The engineering of biology is the technology of this century. To paraphrase a certain rock band of the last century – ‘it’s going to be a long strange trip.’

Conflicts of Interest (COI) for Pamela Silver

Founder:

KulaBio

64X

Petri

General Biologics

Circe

SAB and other:

MITRE

Conagen

Replay