Ravishankar Ramachandran, Ph. D.

Chife Scientist,Molecular and Structural Biology,Sophisticated Analytical
Instrument Facility

Understanding Molecular Mechanisms Using
Structural Biology Approaches

My laboratory elucidates molecular mechanisms underlying key pathways from human pathogens like Mycobacterium tuberculosis using X-ray crystallography, biochemical/biophysical studies, NMR, and rational structure-based computational analyses. The results are subsequently translated using rational structure-based computational approaches to develop inhibitors with therapeutic potential and new mode(s) of action.

Development of new anti-TB therapeutics presents a huge challenge primarily because of the pathogen's ability to evade and persist in the human host for years/decades in a latent/persistent state. Long treatment durations of 6-18 months involving a cocktail of drugs are administered to the patient. Non-compliance has primarily led to the development of Multi- drug resistant (MDR), Extremely drug-resistant (XDR), and even Totally drug resistant (TDR) TB strains. Some of the lab's ongoing work is centered around DNA Base Excision Repair (BER), EsX/TypeVII secretion systems, Feast/Famine regulation, Factors implicated in TB persistence, etc. Since the current crop of anti-TB drugs are not known to primarily act on these pathways, development of new compounds that interfere with these factors represents a strategy to overcome present drug-resistance issues.

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