Department: Biological Sciences (DBS)
Email: dassarmaj [at] iiserkol.ac.in
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My laboratory is involved in the study of neuropathogenesis of murine Coronavirus, mouse hepatitis virus (MHV) infection which causes central nervous system (CNS) demyelination and consecutive axonal loss and mimics certain pathology of human neurological disease Multiple Sclerosis (MS). Demyelination is the process by which axons lose their normal insulating myelin. Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Our laboratory is focused to understand the genomic control of disease phenotype of the MHV strains to empathize the cellular and molecular mechanism of viral induced demyelinaiton in experimental animal model of MS, where we are investigating; 1) how acute viral infection initiate innate immune activation in the CNS which in turn can lead to chronic demyelination with or without involving the adaptive immune system; 2) whether cleavage and fusion properties of the spike protein plays any role in viral spread and neuronal tropism from gray to white matter and preferential neuronal tropism in the white matter can cause demyelination; 4) whether cell-cell interactions in the CNS through gap junction plays any role in neuroinflammatory cascade of MHV induced demyelination. In order to conduct these investigations, we have the important tools of a well developed animal model system and reverse genetic systems of MHV with which to manipulate the viral genome. Our lab has extensive experience in making recombinant strains, phenotypic and pathological characterization of recombinant strains, including fusion, spread to neural tissues and differential neural cell tropism of isogenic recombinant strains in brain, spinal cord and optic nerve. We also have expertise in molecular, cellular, and in vitro neuronal cell and glial cell culture techniques required for our investigations. Our combined studies on the correlation between the genomic control of biologic phenotype of the MHV strains with demyelination and axonal pathology of mouse CNS in neuroinflammatory cascade will be able to establish a powerful approach to elucidate the cellular and molecular details regarding the pathogenesis of MHV induced neurological dystrophy. My long term goal is to extend these studies to search for similarities in mechanistic pathways of the inflammatory processes associated with autoimmune diseases such as multiple sclerosis, neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, and other infectious diseases. The insights from my studies will provide me proper knowledge and expertise to meet the challenge of future emerging neurotropic viruses and viral diseases.
