Dr. Liu received his Ph.D. in chemical biology from University of Pittsburgh, Pennsylvania, in 2017. Prior to that, he received his B.S. in bioinformatics from Huazhong University of Science and Technology, China, in 2011. His current research interest is to apply genetic and genomics techniques to study mechanisms of brain tumor evolution.
2007 – 2011 B.S.
Huazhong University of Science and Technology
2017 - present
The Jackson Laboratory for Genomic Medicine
We report the genetic incorporation of caged cysteine and caged homocysteine into proteins in bacterial and mammalian cells. The genetic code of these cells was expanded with an engineered pyrrolysine tRNA/tRNA synthetase pair that accepts both light-activatable amino acids as substrates. Incorporation was validated by reporter assays, western blots, and mass spectrometry, and differences in incorporation efficiency were explained by molecular modeling of synthetase-amino acid interactions. As a proof-of-principle application, the genetic replacement of an active-site cysteine residue with a caged cysteine residue in Renilla luciferase led to a complete loss of enzyme activity; however, upon brief exposure to UV light, a >150-fold increase in enzymatic activity was observed, thus showcasing the applicability of the caged cysteine in live human cells. A simultaneously conducted genetic replacement with homocysteine yielded an enzyme with greatly reduced activity, thereby demonstrating the precise probing of a protein active site. These discoveries provide a new tool for the optochemical control of protein function in mammalian cells and expand the set of genetically encoded unnatural amino acids.