Verma Lab @CSIR-CDRI
Welcome Visitor No.
Mitochondrial miRNA and Ageing
The biological basis of ageing remains one of the most sought after scientific questions. The past decades have witnessed major leaps and bounds in our understanding of the cellular and molecular mechanisms of ageing using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial functions, are amongst the key regulators of ageing. However, the intricate details linking mitochondrial dysfunction and ageing are yet to be fully elucidated. A plethora of miRNAs have been identified, which both positive and negatively modulate longevity in the invertebrates, Caenorhabditis elegans and Drosophila. As there exists a dynamic interaction between the miRNAs and mitochondria, mitochondria associated miRNAs (mitomiRs) can be considered as novel and significant players in regulating the ageing processes.
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We aim to understand the mitomiRs dynamics over the course of natural ageing using C. elegans model system. More specifically, our laboratory is interested in elucidating the possible effects of mitomiRs on ageing and age associated pathologies along with the cellular and molecular mechanisms; tissue specificity and evolutionary relevance. Age-associated novel mitomiRs and their targets will be discovered using Deep-Sequencing of small RNAs, high-throughput data analysis, target prediction, and microscopy. This information will further be utilized to develop genetic and pharmacological interventions to study the functional aspects of mitomiRs in regulating aging in C. elegans.
MitomiRs, microglia, and neuro-inflammation
Microglia, a specialized population of macrophage like cells in the central nervous system (CNS), accounts for 5-10% of cellular mass constituting the brain. These cells participate in immune responses within the CNS, and also aid to the sustenance of normal brain functions under healthy conditions. Chronic microglial activation has immense impact on the progression of neuro-inflammation and degeneration of brain cells. Few reports have emerged that suggests mitochondrial dysfunction in microglial cells as an inducer of neuro-inflammation in animal models of Alzheimer’s and Huntington’s disease. The exact mechanisms governing the activation of microglial cells and the resultant effects on the neuronal survival remains largely unexplored. Recent reports have hinted at the role of miRNAs affecting mitochondrial function in brain cells of animal models of Alzheimer’s disease and Parkinson’s disease. However, the precise relationship between mitomiRs and microglial function in neuro-degeneration still needs to be established.
Using rodent models of neurodegenerative diseases, our laboratory aims at identifying mitomiRs in brain derived microglial cells. Multi-omics will enable us to understand whether it is possible to modulate mitochondrial function in microglial cells in order to prevent neuronal death. Our approach combines flow cytometry, transcriptomics, proteomics, and bioinformatics tools to understand the mechanistic aspects of mitomiRs for regulating microglial functions in neurological and neurodegenerative disorders.