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Infectious Diseases Development of live attenuated vaccines for intracellular parasitic diseases: Generation of live attenuated vaccine candidates, for the diseases due to intracellular parasites is a major focus of our group. Pathogens are attenuated by gene deletions in order to make defined and stable alterations in the genome. The gene targets for deletions would be specific to growth and or virulence of the pathogens. Initial focus is to develop vaccines for visceral leishmaniasis (VL). VL is endemic to India. The mutant parasites will be tested as vaccine candidates for its safety and efficacy in the appropriate animal models viz., mice, hamsters and langur monkeys. Protective immune responses against the vaccine candidates will also be analyzed.Principal Investigator: A. Selvapandiyan
Gene characterization via RNAi in Trypanosomatids: Characterization of genes could lead to the development of more sensitive and affordable drug targets and vaccines. Attempts to carryout RNAi based gene characterizations have failed in Leishmania donovani and L. major because of the lack of RNAi machinery in such parasites that cause Visceral and Cutaneous leishmaniases respectively. However, RNAi works in Trypanosoma brucei, that causes Sleeping sickness in Africa, an another Trypanosomatid member like Leishmania. This project uses T. brucei as tool to characterize genes of Leishmania. Principal Investigator: A. Selvapandiyan
Molecular mechanism of Mycobacterium tuberculosis pathogenesis: Focus is to understand the regulation of extracellular function sigma factors particularly the ones which are involved in regulating M. tuberculosis bacterial DNA replication and repair under stress. Focus also is to study the bacterial proteins that are involved in DNA replication and repair and are induced during macrophage infection. Understanding of these pathways will lead insights into the strategies the bacteria adopt to evade immune system and establishment of infection. Principal Investigator: Krishna Murari Sinha Molecular mechanism of membrane fusion: Cellular membrane fusion is one of the most common ways for molecules to enter or exit cells, in processes such as fertilization and viral infection. When two cells fuse together, their membranes come together at one location and create a connection between the cells that allows the exchange of material between them. Eventually, the two membranes form one single, continuous membrane surrounding the contents of both cells. Knowledge about membrane fusion could help develop systems in which a drug or gene of interest is enclosed in a membrane known to fuse with specific cells in our body, thus facilitating drug delivery or improving gene therapy. Understanding cell fusion may be key to preventing viral infection also. So we want to study the determinants or residues of fusion proteins involved in fusion process. Principal Investigator: Anuja Krishnan Mapping of serotype specific Dengue virus neutralizing epitope for the development of safe and efficient vaccine candidate: Major complication in Dengue virus infection is that many poorly neutralizing or non-neutralizing antibodies against one serotype are cross-reactive which results in enhancement of disease on infection with another serotype. Aim is to identify serotype specific epitopes involved in antibody mediated neutralization of Dengue virus infection which could lead to an understanding of disease processes and to vaccine development. Principal Investigator: Anuja Krishnan Conversion of non-virulent resident microbes into opportunistic pathogens in the absence of any genetic changes: Interest is using an in vitro locked-in mutant of commensal E.coli as control, deciphering molecular mechanisms and cellular signatures in bacteria undergoing commensal-pathogen transition. Principal Investigator: Sudeshna Kar
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