Genetically Encoding New Bioreactivity

Friday, November 21, 2014 - 2:00pm
Fung Auditorium, Powell-Focht Bioengineering Hall
Lei Wang Ph.D.

Associate Professor of Pharmaceutical Chemistry,
University of California, San Francisco


Genetically Encoding New Bioreactivity


The genetic code can be expanded to include unnatural amino acids (Uaas) by engineering orthogonal components involved in protein translation. To be compatible with live cells, side chains of Uaas have been limited to either chemically inert or bio-orthogonal (i.e., nonreactive toward biomolecules) functionalities. To introduce bioreactivity into live systems, we engineered the genetic code to encode a new class of Uaas, the bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled bioreactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems. These diverse bioreactivities, inaccessible to natural proteins, open doors to novel protein engineering and biological research.


Lei Wang received his PhD from UC Berkeley under the guidance of Peter G. Schultz. His graduate research resulted in the first expansion of the genetic code to include unnatural amino acids (Uaas) in 2001, for which he was awarded the Young Scientist Award by the journal Science. After postdoctoral training with Roger Y. Tsien, Wang started his group at the Salk Institute in 2005, and moved to UCSF in 2014. His group has developed new methods for the expansion of the genetic code in a variety of cells and model organisms, including mammalian cells, stem cells, C. elelgans, and recently embryonic mouse. Wang discovered that release factor one is nonessential in E. coli, and engineered autonomous bacteria capable of incorporating Uaas at multiple sites with high efficiency. By proposing the concept of proximity-enabled bioreactivity, Wang designed and demonstrated that a new class of Uaas, the bioreactive Uaas, can be genetically encoded in live systems. These bioreactive Uaas enable bioreactivities, inaccessible to proteins before, to be specifically introduced into biosystems, opening the door for new protein engineering and biological research in vivo. Wang is a Beckman Young Investigator, a Searle Scholar, and an NIH Director’s New Innovator Awardee.