Abhishek Chatterjee

Building New Tools to Read and Write Eukaryotic Biology with Chemistry, Viruses, and Molecular Evolution

Our group combines elements of chemical biology, synthetic biology and virology to develop new strategies for understanding and manipulating biological processes in mammalian cells. One particular focus is the genetic code expansion technology, which allows site-specific incorporation of enabling noncanonical amino acids (ncAAs) into proteins in vivo. We are expanding the scope of this technology through: 1) the development of ‘universally orthogonal’ engineered aminoacyl-tRNA synthetase/tRNA pairs to genetically encode previously inaccessible ncAAs in both eukaryotes and bacteria, 2) generating viral vectors that efficiently deliver the ncAA-incorporation machinery into mammalian cells and tissues, 3) establishing technology for site-specific incorporation of multiple distinct ncAAs into one protein in mammalian cells, and 4) the development of a powerful mammalian cell-based directed evolution platform to improve the intrinsic performance of the ncAA-incorporation machinery. We are also interested in applying our technology to several biological systems that are refractory to traditional genetic toolbox such as: 1) understanding and engineering the molecular processes associated with the entry of adeno-associated virus into human cells, and 2) elucidating the roles of various post-translational modification of mammalian proteins.