My group focuses on unique aspects of the translational apparatus of mycobacteria.
GatCAB dependent tRNA synthesis: Unlike all eukaryotic cytosols, and some model bacteria such as E.coli, mycobacteria lack two specific tRNA synthetases – enzymes that attach amino acids to their cognate tRNA molecule – for glutamine and asparagine. A two-step synthesis, first a physiological misacylation by a non-discriminatory synthetase, followed by transamidation by the GatCAB enzyme complex ensures fidelity of the genetic code. We are investigating possible ways to exploit this difference in mycobacterial physiology to model antibiotic action.
Adaptive mistranslation: Despite the best efforts of the cell to ensure that newly synthesized proteins accurately reflect their coding genes, errors occur, resulting in mistranslated proteins. We have shown that mycobacteria are remarkably resilient to these translational errors, and that the newly expanded ‘protein repertoire’ of the cell can result in certain adaptive phenotypes. We are actively exploring these phenomena to better understand the role that mistranslation may play in mycobacterial adaptation to hostile environments.