We genetically encode unnatural amino acids in live cells and organisms to investigate biological processes in their natural settings and to develop new biotherapeutics.
The Wang Lab 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. elegans, and embryonic mouse. A key development is the use of type-3 pol III promoters (e.g., H1 and U6) for expressing prokaryotic tRNA in eukaryotic cells, which has proven generally useful for code expansion in yeast, mammalian cells, and invertebrate and vertebrate animals. The lab team discovered that release factor one (RF1) is nonessential in E. coli and engineered autonomous bacteria capable of incorporating Uaas at multiple sites with high efficiency. By developing the concept of proximity-enabled bioreactivity, the Wang Lab designed and demonstrated that a new class of Uaas, the bioreactive Uaas, can be genetically encoded in live systems. These bioreactive Uaas enable novel covalent bonding abilities to be specifically introduced into proteins and biosystems, opening the door for new protein engineering, biological research, and therapeutic application in vivo.
Combining chemistry with molecular and cell biology, we are designing and genetically encoding new amino acids for in vivo investigation of protein signalling and for the development of new biotherapeutics.
Proteins are the major workhorse for biology and thus implicated in various diseases. Expanding the genetic code to incorporate novel amino acids into proteins enables us to manipulate proteins at the atomic scale in their native habitat with new properties overcoming natural limit. This unprecedented precision and barrier-breaking power thus opens enormous possibilities to transform both basic biological research and therapeutics.
The work of the Wang Lab is well integrated into and supported by the special academic environment at UCSF, which focuses on biomedical sciences and health. Our research into protein signalling can reveal underlying mechanisms for pathological conditions, and research into biotherapeutics can lead to innovative drugs for diseases.
Lei Wang, PhD, has been engineering the genetic code since 1997. His PhD research with Peter Schultz resulted in the first expansion of the genetic code (Science, 2001, 292:498-500), for which he was awarded the Young Scientist Award by Science (Science, 2003, 302:584-585). Wang is also a 2006 Beckman Young Investigator, a 2006 Searle Scholar, and a 2008 National Institutes of Health Director’s New Innovator Award recipient. The members of the Wang Lab have a wide breadth of expertise in organic chemistry, molecular biology, cell biology, and neuroscience. The Wang Lab encourages interdisciplinary collaboration, values innovative technology development, and pursues biological questions in depth.