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Molecular and systems level understanding of regulatory networks in pathogenic microbes


 I. Understanding regulatory mechanisms pertaining to microbial pathogenesis



Part A:  Understanding the network of transcriptional and translational regulation

  • Global regulators contributing to M. tuberculosis pathogenesis
  • Exploring NME- pathway of M. tuberculosis and riboflavin biosynthesis pathway of Vibrio as anti-bacterial target
  • Cross-talk  of different M. tuberculosis hemoglobins with cellular components: implications on pathogenesis
  • Glycosylation of proteins as PTM and its relevance in M. tuberculosis pathogenesis

Part B: Phenotypic switching-assisted drug resistance

  • Genetic pathway of M. tuberculosis involved in  drug- resistant biofilm formation
  • Molecular basis of amphotericin B resistance in biofilm forming cells of C. albicans: genes that contribute to AmpB resistance
  • Protein kinase signaling cascade and its contribution to antimicrobial resistance, pathogen survival and virulence of multi-drug resistant  Acinetobacter baumannii
  • Exploring budding yeast as a model for functional exploration of virulence determinants from gut pathogenic bacteria



II. Dissecting host-pathogen interactions in the context of virulence


  • Host pathways that determine the availability of micronutrients

  • Influence of pathogenic factors on the innate immunity pathways such as authophagy and/or authophagic response

  • Modulation of cytokine profiles by secretory virulence factors

  • Role of endocrine factors in modulation of immune system in the infectious disease




III. Exploring unconventional methods to design and develop novel disease prevention strategies


The currently available BCG vaccine is one of the most widely used vaccine throughout the world. However, the efficacy of this vaccine is highly variable ranging from 0% in South India to 60% in the Western world. Recently, CSIR-IMTECH has demonstrated that supplementation of BCG with IL-7 and IL-15 substantially improved its protective efficacy by enhancing T-cell memory response. In this proposal, we wish to evaluate prophylactic and therapeutic efficacy of recombinant BCG strains secreting the cytokines IL-7 and IL-15 in animal models and human PBMCs





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