Ratnaparkhi Group

      Indian Institute of Science Education & Research (IISER)

Pune, INDIA

    Animals as different as humans, worms and flies use remarkably similar molecular mechanisms to control their development. Discoveries of developmental paradigms in one organism have provided insights into development processes of other organisms. We utilize Drosophila melanogaster as a model organism to study common molecular principles underlying animal development and disease.


      SUMO, the small ubiquitin like post-translational modifier has been found to modify 10-30% of all eukaryotic cellular proteins, withe the SUMO proteome varying with cell type, developmental stage and cellular milieu. We are studying roles for SUMO in regulating host defense mechanisms. With this in mind, as  a first step, we have used quantitative proteomics to measure changes in the SUMO proteome in response to an immune challenge. We find that proteins that change their SUMOylation status on infection include a wide range of proteins involved in immune signaling pathways as also proteins involved in protein synthesis, trafficking and metabolism. Our current focus is to demonstrate biological roles for  SUMOylation in proteins by exchanging target lysines to arginine. This is being done for a dozen targets in the laboratory by CRISPR/Cas9 based genome editing.


        Gene duplication, expansion and subsequent diversification are features of the evolutionary process. Duplicated genes can be lost, modified or altered to generate novel functions over evolutionary time scales. These features make gene duplication a powerful engine of evolutionary change. We are exploring these features in the sixteen member Drosophila MADF-BESS family of transcriptional regulators. The family is represented by proteins that contain a N-terminal DNA binding MADF domain and a C-terminal, protein interacting, BESS domain. Our findings indicate that the family has evolved from a common ancestral gene that has duplicated and expanded in Drosophila. The members of the family are transcriptional factors that have sub-functionalized and currently appear to have diversified roles in different developmental stages and varied transcriptional networks in in cell fate specification. Many subsets of the genes are expressed in the same cell and demonstrate partial redundancy in terms of biological function.


         Our laboratory is also trying to establish the mechanistic basis behind the onset of Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig’s Disease), a neurodegenerative disease that affects motor neurons. Our model for the disease is the 8th locus discovered for ALS, the VAPB locus. The VAPB(P56S) mutation causes ALS in humans and we are studying cellular perturbations caused by expression of this mutant variant in the nervous system of flies.  We have used Drosophila reverse genetic screens to identify interactors of VAP and have identified a 400 member Gene Regulatory Network (GRN) for VAPB. Our efforts are currently focused on trying to understand the dynamics of VAPB(P58S) protein aggregates in the cell, with a emphasis of TOR signaling, which we discover is a regulator of VAPB function in neurons.