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.

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 number 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.

We are particularly interested in answering the following questions:

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:

  • Is it possible to halt and/or reverse this aggregation?

  • If yes, how does this influence aging or healthy lifespan?

  • How proteotoxicity in one tissue is recognized by distant tissues?

  • 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 model system.

A tiny worm as model organism

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The Caenorhabditis elegans is an ideal model organism to study aging, stress response and protein quality control because of its short lifespan (3 weeks), limited number of cells, transparent body, easy genetic manipulation and most importantly, conservation of genes and pathways implicated 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.

A Brief Introduction to C. elegans (by OpenWorm)

About Dr. Prasad KASTURI

Before joining IIT-Mandi as a faculty, Dr. Prasad worked with Prof. Ulrich HARTL at Max-Planck Institute for Biochemistry, Germany, where he got trained in the filed of protein homeostasis. He also involved in establishing and leading C.elegans facility.

 

He received his PhD from University of Fribourg, Switzerland (where he was introduced to C.elegans work).

He obtained his MSc from School of Biotechnology, Madurai Kamaraj University. [more]

CONTACT

Bio-X center, School of Basic Sciences

Indian Institute of Technology-Mandi

South campus, Kamand

175005, Himachal Pradesh

INDIA

E-mail: prasadkasturi (at) iitmandi.ac.in

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© 2020 by Prasad Kasturi