Welcome to Neuroscience Group, IISER-Kolkata

Jayasri Das Sarma

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:: Research ::

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:: Research ::

Molecular and Cellular Virology: Neurological dysfunction is a manifestation of several neurodegenerative and autoimmune diseases of the nervous system, such as Alzheimer's disease, Parkinsons disease, HIV-1 associated encephalopathy and in Multiple Sclerosis (MS). Of these, MS is one of the most common demyelinating diseases of the human central nervous system (CNS) afflicting about 400,000 people in the United States, primarily in the age group of 20 to 45. The pathophysiological mechanisms underlying the changes in neurological function are as yet unresolved, but may include neuroinflammatory responses to infectious and/or environmental, as well as endogenous factors. My laboratory is interested in identifying and characterizing the molecular and cellular pathways involved in the neuroinflammatory mechanisms of MS, which can provide insights for therapeutic inventions.

Long standing hypotheses on the etiology of MS suggest that an infectious agent encountered during adolescence primes a disease process that later appears in the adult after a variable period of quiescence, when the viral particle may or may not be present. It is not known what can be the intervening stages between early age viral infection and later induction of demyelination. A better insight into the molecular and cellular mechanisms of these processes leading to MS lies in the systematic study of animal models. Towards this goal several experimental animal models have been developed to study the mechanisms of virus-induced demyelination, including the coronaviral mouse hepatitis virus (MHV) infection. Infection of mice with neurotropic strains of MHV induces a biphasic neurological disease with acute meningoencephalitis, followed by chronic inflammatory demyelination which mimics the pathology of MS. In MHV induced neuroinflammatory model, demyelination develops when virus is cleared and encephalitis is resolved. My research interest is focused on identifying the factors and the pathways used by the MHV to establish the acute stage encephalitis and the later stage disease process on two levels. First, what are the genomic controls of the early stage disease process? Here, using targeted RNA recombination we are generating recombinant strains of MHV with different encephalitic and demyelinating properties to study mouse CNS pathophysiology. Second, for mechanistic studies we use different phenotypic strains to understand how the variation in the genomic control (viral factors) can influence the later events of CNS cellular destruction processes. Understanding the correlation between the early stage of encephalitis and chronic stage demyelinating disease and the viral factors which may contribute to the disease progression is helping us to define pathway(s) underlying the pathological mechanism of MHV induced neuroinflammation.

The studies are being extended to human viruses that show high seropositivity during MS infection. Specific viral genes that interact with human locus are being targeted for virology and cell biology studies based on leads from bioinformatic analysis. By building parallels between mechanism of infection in human and mouse our goal is to build testable hypothesis that can help us gain better insight into MS and possibilities of better therapeutic intervention.