School of Biosciences and Bioengineering
Indian Institute of Technology, Mandi
Protein Quality Control during Aging
The main focus of our lab is to explore the molecular mechanisms of proteome protection that help in extending healthy lifespan using C. elegans model
Proper functional balance of the cellular proteome (protein homeostasis or proteostasis) is vital for all living cells. Protein quality control (PQC) systems coordinately monitor and protect the proteome. However, maintaining a functionally balanced proteome is a challenging task, especially in the face of various external and endogenous stress that accumulate during aging.
Aging is a major risk factor for a number of diseases such as cancer, diabetes and neurodegenerative diseases. The major pathological hallmark of these disorders is the protein misfolding and aggregation (proteotoxicity) due to the compromised protein quality control or proteostasis. The signaling pathways that regulate stress responses and aging, are also found to modulate proteostasis. A better understanding and connection of the molecular mechanisms that protect the proteome and modulate aging would help promoting healthy long lifespan.
THE QUESTIONS OF INTEREST IN OUR FIELD
Proteome-wide aggregation occurs during stress and aging. Typically stress-induced protein aggregation can be resolved once the stress has abated. However, the fate of protein aggregation that occurs during aging is difficult to anticipate, which raises a few important questions:
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Is it possible to halt and/or reverse this aggregation?
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If yes, how does this influence aging or a healthy lifespan?
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How proteotoxicity in one tissue is recognized by distant tissues?
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What are the molecular mechanisms that are involved in communicating the stress and priming a stress response?
We would like to answer these questions using C.elegans as a model system.
A TINY WORM AS A MODEL ORGANISM
The Caenorhabditis elegans is an ideal model organism to study aging, stress response, and protein quality control because of its short lifespan (3 weeks), a limited number of cells, transparent body, easy genetic manipulation and most importantly, conservation of genes and pathways implicated in human aging and diseases. [more]
We use C.elgans models and apply various genetic, molecular biology, and biochemical methods such as RNAi, gene editing by CRISPR, proteomics as well as microscopy.