In collaboration with Systems Immunology Laboratory, National Institute of Immunology, New Delhi, we are interested in making and analysing mathematical models of NFkB signalling pathways in the context of inflammatory and developmental cues in different cell-types. Our aim is to look at different mechanistic aspects and possible implications of NFkB pathway crosstalk or absence of it, in cellular physiology and pathology with the help of systems level dynamical models.
Neurodegenerative disease network modelling: Neurodegenerative diseases are hereditary and sporadic conditions that are characterised by progressive neuronal cell death caused by the aggregation of abnormal proteins. In a cell, there is complex interaction of large numbers of protein molecules present to persuade cellular functions. Cellular functions are controlled by genetic networks. Mutation in genes, expressing proteins cause aberrations in cellular functions and cause diseases. Hence, disease network modelling helps in carrying out systemic analysis of how alteration in genetic networks cause diseases.
Amyotrophic Lateral Sclerosis, a motor neuron disease, is one of the most sought after problems in biology. Even after decades of research, a definite mechanism to elucidate the pathogenesis of the disease is not available. Although advances in research has thrown some light upon and it is now clear that it is a disease with multiple metabolic dysfunction in motor neurons. We are trying to look into the relationship between the autophagy and apoptosis. How does the cell balance both process and how does environmental perturbations affect them. We are also keen to know the effect of such conditions on the neuromuscular junction as it is the point where the manifestation of the ALS starts. Using computational modelling of the involved pathways and experimental observation in the motor neurons, we are trying to understand which components of molecular machinery are major players in the pathogenesis.
Significant knowledge gap exists about the genetic information of Indian ALS patients Indian ALS patients exhibit certain distinctive characteristics, which include early disease onset and progression, and show prolonged survival, thereby implicating a relatively slow disease course. Therefore, it would be interesting to study the genetic causes of ALS onset and progression in Indian patients. Our study provides a unique opportunity to understand the disease from a diverse genetic, ethnic and demographic perspective.