Research

RESEARCH AREAS | COLLABORATORS | FUNDING AGENCIES

RESEARCH AREAS

Mitochondrial structure-function alterations in human disease conditions

Compartmentalization of cellular contents into functional units called organelles is an essential feature of eukaryotic cells. One of the most critical organelles of a cell is the mitochondrion, which harbors TCA cycle and oxidative phosphorylation machinery for energy production. Biosynthesis of cellular building blocks such as nucleotides and amino acids along with Ca2+ ion buffering also requires active mitochondria. Interestingly, mitochondrial shape and dynamics have been reported to have a profound role on the abovementioned functions. Mitochondria are dynamic in nature whose morphology is maintained by a continuous process of division and fusion. An intricate relationship between mitochondrial function and dynamics has been reported and is an important aspect of investigation in several human diseases such as neurodegeneration. Using yeast as a model, we are trying to understand the effect of altered mitochondrial dynamics caused due to disease conditions in relation to the protein structure and function.

Age-associated neurodegeneration and the role of subcellular organelles

Neurodegenerative conditions are associated with ageing. Several age-associated alterations in cell organelles have also been reported. We aim to understand these two processes in connection to each other. For this, we are looking at Parkinson’s disease models and trying to understand if the disease condition is caused/exacerbated due to alterations in organelles. Alpha-synuclein expressing yeast cells are a good parkinson’s disease model as several pathways effected in the disease condition are conserved across eukaryotes. Studying yeast homologs of the disease-causing proteins will also enable us to understand the disease mechanism.

Peroxisome Biogenesis

Peroxisomes are unique organelles in a way that they can adapt their functions based on the cell type and organism. The last decade has seen major advancement in our understanding of various aspects related to the biogenesis of peroxisomes. Peroxisomes are formed by growth and division of pre-existing organelles. The role of ER in the formation of peroxisomes is also now accepted, though the exact contribution of this is yet to deciphered. Several peroxins have been identified and their role in protein import, membrane formation, division, degradation has been identified. Post translational modifications (PTM) of peroxins have been reported that regulate the function of these proteins. We are aiming at identifying PTMs in peroxins involved in peroxisome biogenesis and understand the effect of such modifications on the structure and function of the proteins.

Role of peroxisomes in yeast replicative and chronological lifespan

Ageing is an inevitable degenerative phenomenon characterized by a progressive decline in the optimum functioning of a cell which ultimately leads to irreversible cellular damage and cell death. A combination of genetic and environmental factors and various disease conditions act as the contributors of age-associated cellular changes. Yeast in general and Saccharomyces cerevisiae in particular has become an attractive eukaryotic model organism for studying the hallmarks of cellular ageing owing to its simplicity, the ease to perform genetic and molecular manipulations and its relative short lifespan. A role for several sub-cellular structures as vacuole, mitochondria in ageing has also been proposed. Peroxisomes in a cell are also a major contributor for the production and scavenging of ROS. ROS accumulation is an important phenotype associated with ageing. Using yeast as a model we are trying to understand the role of peroxisomes in both chronological and replicative life span of yeast.