A key focus of the group is on the protein degradation machinery that helps to maintain proper level of proteins (protein homeostasis) in Mycobacterium tuberculosis, the causative agent of TB, the world's single largest infectious killer that is annually responsible for 1.5 million deaths. The questions we aim to answer are:
1) What is the assembly mechanism of the M. tuberculosis proteasome core particle and its regulatory particles?
2) What is the role of allostery and long-range interactions in the machinery that tags substrates for proteasomal degradation?
3) How are substrates selected for tagging and degradation?
4) What is the molecular basis of antibiotics that operate by disrupting proteasomal protein degradation?