Translational Health

MEDICAL BIOTECHNOLOGY / Recombinant Diagnostics and Vaccines

Research Interests

Tuberculosis, Immunology, Proteomics, Metabolomics, Metallomics, Therapeutics

Description of Research

Anemia of inflammation in Tuberculosis: Iron is a critical component for the basic survival of both host and pathogen. The host has evolved a complex mechanism involving major proteins (hepcidin, ferroportin, transferrin, DMT1, Nramp1, ferritin and others) to limit access of iron for pathogen survival. In parallel, the pathogen has also developed a strategy to alternately acquire or retain iron in anaemic conditions. The group’s preliminary data suggest that existing approved metal chelators could be useful for further limiting iron access to Mycobacteria for its survival in infected mice model systems and exploring their mechanism of action at molecular levels.

Contribution of immuno-senescence (in ageing) and chronic inflammation (in diabetes) to tuberculosis susceptibility: Ageing leads to profound changes in the body’s immune milieu, causing immune-senescence, and significantly increases a person’s susceptibility to reactivation of latent disease, or rapid progression to active tuberculosis (TB) disease. Reports showed decreased neutrophil count and monocyte functions, altered function in peripheral T lymphocytes and loss of naive T cells in aged mice models and humans. The group aims to understand and correlate the age-associated decline in immunological parameters and its contribution to TB susceptibility in human and in murine models of TB representing varied age groups. While type 2 diabetes mellitus (T2DM) has long been associated with a higher risk for TB infection and adverse disease outcomes, the underlying mechanisms of this susceptibility are poorly understood. In this project, using patients and animal models, we will try to understand the core mechanisms ruling the immune insufficiency in TB-DM at the cellular and molecular levels. Understanding the altered host immunity in aged and T2DM subjects might be useful to develop age or TB-DM appropriate therapeutic solutions for these co-morbid TB patients.

Alveolar type-II epithelial cells as niche for Mycobacterium survival:  Like immune cells, type-II epithelial cells also represent a niche for Mycobacterial infection. The group uses optimised methods for infecting alveolar epithelial cell lines (A549) with different laboratory and clinical Mycobacterial strains to monitor the intermediates of central carbon metabolism and to probe the mitochondrial functional dynamics. The group employs carbon labelling (13C) and flux balance analysis (FBA) to monitor the glycolysis, TCA cycle and OXPHOs metabolism in control and infected A549 cells. Using inhibitors, the group aims to identify the critical host metabolic pathways to eliminate pathogens by modulating the energy kinetics.

Gut microbiota and their byproducts as nutrient supplements in tuberculosis: Employing metagenomics and metabolomics tools, the group observed microbial dysbiosis and deregulated fecal metabolites in tuberculosis patients and in in vivo model systems which partially resolve during therapeutic interventions. The group is confident to demonstrate the importance of gut microbiota and its by-products in resolving infectious disease conditions like tuberculosis.

Developing eNOSE for tuberculosis screening: Using exhaled breath volatile organic compounds as markers, the group is collaborating with a start-up company and an established player in this field with expertise in sensor, electronics designing and decision-making tools. The group is in the process of developing an eNOSE for further refinement and testing with clinical collaborators in India.

The Group has recently demonstrated diverse pharmacogenomic patterns existing in tuberculosis patients and control subjects from Indian North Eastern states (Tripura, Nagaland and Manipur).

Recent Publications