Abstract

Inaugural Talk- Targeting Topology Modulators to Counter Resurgent Tuberculosis

V Nagaraja, Professor, Indian Institute of Science

Tuberculosis continues to be a major global health concern with millions of deaths and new cases added annually. The emergence of multiple, extensive and total drug resistant strains of Mycobacterium tuberculosis has resulted in worldwide efforts to combat the disease using a variety of strategies. First I will describe some of the global multi-centric efforts to find novel therapeutics and vaccines. Then describe some of our own efforts to understand the pathogen and to exploit the knowledge to develop inhibitors targeted against the dreaded pathogen. The DNA within the cell is subjected to supercoiling and compaction. Topoisomerases, a dedicated bunch of enzymes, catalyse the supercoiling, required during the genome duplication and when genes are expressed. In addition, nucleoid associated proteins(NAPs) bind DNA to participate in topology modulation by organizing the genome into a more compact form. Understanding how the topoisomerases and NAPs function in mycobacteria to ensure topological homeostasis has been a major topic of our study in order to exploit them as drug targets. A combination of approaches- bioinformatics, genetics, molecular and cell biology as well as structural elucidation to study the function of these essential proteins in mycobacterial is undertaken. Some of these efforts will be described.