The genetics of the mitochondrion: uncovering its role in neurodegeneration and aging

Faculty: Debnath Pal (CDS) & Shweta Ramdas (CBR)

The mitochondrion is the energy-producing part of the cell, and plays a crucial role in cellular processes. Dysfunction of the mitochondrion has been strongly linked to aging, and age-related disorders. The mitochondrion carries its own copy of the genetic material that is inherited maternally. Though small, this genome has an outsized effect on cellular and organismal function.

In this project, we propose to study the impact of genetic variation in the mitochondrion on the risk of age-related disorders (in particular neurodegeneration) and other traits. We will work with genomic data from thousands of individuals that have been tested for physiological and cognitive traits to understand the role of mitochondrial DNA—its genetic variation, its predisposition to mutations, and the number of copies in an individual–, and the cross-talk between the nuclear and the mitochondrial genomes in aging.

This project is at the interface of biology and data science. It is primarily computational, and involves using creative statistical and bioinformatic approaches to process, analyse, and interpret multi-modal complex datasets from human genetics. These approaches will point us to unique genetic risk factors for aging in the Indian population, and point us to mechanisms of genome evolution.

A helpful reference:

Mitochondrial DNA variation across 56,434 individuals in gnomAD: 10.1101/gr.276013.121