Associate Research Professor, Biodesign Center for Bioenergetics
Larisa Dedkova came to the Biodesign Center for BioEnergetics at the Biodesign Institute in 2010 from Virginia, where she worked from 2003 until 2009 at Pinnacle Pharmaceuticals focusing on antibacterial drug discovery. As a team leader, Dr. Dedkova was responsible for developing high-throughput screening assays which allowed identifying new antibacterial agents with different mechanisms of action. She participated in identification of several novel compounds with in vitro and in vivo efficacy against MDR human bacterial pathogens. Before that, Dr. Dedkova participated in 4 different projects over 3 years dealing with incorporation of unnatural amino acids in proteins for deep study of structure-function relations of such proteins as topoisomerases and firefly luciferases. To increase variety of unnatural amino acids which can be incorporated in protein, a new approach based on re-engineering of bacterial ribosome was started and during her last seven years the experimental job was focused on this problem. Construction of the library of E.coli cells having plasmid-borne ribosome with random mutations in PTC and selection procedure using the analogue of puromycin gave interesting results. It was shown that specific mutations in ribosome allow to increase the incorporation of some unnatural amino acids (for example, D- and β-) about 5 to10 times. Also, successful selection of modified ribosome allowed us to incorporate different dipeptide cassettes that gave this method a new practical application (for example, construction of new fluorescent protein and peptides).
Synthesis of proteins with unnatural amino acids for study of their function. Applications of modified ribosome approach as in vitro and in vivo.