About Fellow

Weill Cornell Graduate School of Medical Science, New York, USA

Weill Cornell Medical College, New York, USA
University of Cambridge, UK

Institute of Genomics and Integrative Biology, New Delhi

My fascination with tuberculosis and its causative agent Mycobacterium tuberculosis began during my research training at the Department of Biochemistry, University of Delhi South Campus. Immunology and human physiology had been my favourite subjects as an undergraduate; and the entry of a pathogen into these worlds made my love for biology even deeper and defined for me the difference between “physiologic” vs “pathophysiologic”. Simple terms like inflammation gained a new perspective; was it beneficial for the immune system to mount an inflammatory response or was it eventually being used and subverted by the pathogen? This question largely remains unanswered while several specific examples in nature support this conundrum. Nitric oxide is one such “inflammatory mediator”, which also happens to be antimycobacterial. But the pathogen’s genome seems to encode mechanisms that counter this stress. In a genome wide screen to identify mycobacterial genes that confer resistance to nitric oxide, Carl Nathan’s group at Weill Cornell Graduate School of Medical Sciences identified genes in the proteasome locus that seemed to do so. As a young graduate student, inspired in many ways by Carl’s work, I jumped at the opportunity of studying the proteasome of the pathogen. What made it more interesting was that the genes were predicted to be essential so nobody had studied their biology thus far! My mentor Sabine Ehrt had been working on creating a tetracycline inducible gene expression system and this became a useful tool that enabled us to genetically deplete the genes encoding the proteasome. This also gave us the novel opportunity of depleting Mtb genes during infection in mice. Ironically, we found that the proteasome’s proteolytic function was not essential for growth in vitro, rather it is in vivo. In addition, it was not nitric oxide, but starvation against which the pathogen fought using the proteasome. This finding opened a new question for me: how is the pathogen “starved” if the host is rich in nutrients such as fatty acids which the pathogen can utilize. But it was time to move on, in my case to a new continent and conscientiously, to a new field. I needed to learn something new!

My interest in physiology made the choice easier. I chose to focus on studies on molecular mechanisms of insulin resistance and lipodystrophy to gain a broader perspective on human lipid metabolism. I joined the group of Professor Stephen O’Rahilly and Dr David Savage at University of Cambridge. As clinicians, they had been interested in solving the underlying mechanisms of severe insulin resistance and lipodystrophy; this complemented my interest in developing molecular and cell biology tools to understand lipid storage in mammalian cells. This marriage of disciplines resulted in the first ever report implicating a role for altered lipid droplet homeostasis in adipocytes with insulin resistance. This phase of my career introduced me to the power of fluorescence based imaging tools to study molecular phenomenon in situ. 

The prospect of starting my independent scientific career and my unending fascination with tuberculosis and the causative pathogen, brought me to Institute of Genomics and Integrative Biology in New Delhi. I’ve been here for a year now and have been focussing my studies on understanding the nutrient
cross-talk between eukaryotic cells and the intracellular pathogen Mycobacterium tuberculosis. My approach to addressing questions in this field will involve more than genetics and cell biology; the power of proteomics and lipidomics will be harnessed for understanding this nutrient cross-talk between the host and pathogen. Support through the Wellcome Trust-DBT India Alliance Intermediate Fellowship scheme will provide the means for me to expand my expertise and build a team that can answer these pertinent questions of infection biology.