Indian Institute of Science, Bengaluru, India
Indiana University, Bloomington, Indiana, USA
Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad
My research has predominantly focused on post-transcriptional mechanisms of gene expression involving pre-mRNA splicing factors, alternative splicing factors and microRNAs. As a PhD candidate working under the guidance of Prof. Usha Vijayraghavan in Indian Institute of Science, Bangalore, I made use of the single celled Saccharomyces cerevisiae to understand the functioning of a pre-mRNA processing factor(Prp17) in splicing and cell division cycle. My interest in understanding the functional role of splicing regulators in the mammalian model prompted me to join Prof. Douglas L. Black’s laboratory at UCLA/HHMI where I examined the role of alternative splicing factors such as Sam68 and PTB/nPTB in neurogenesis utilizing mammalian cell lines and primary neuronal cultures. Through, these studies I identified novel mRNA targets of a KH domain protein, Sam68 and established a role for this RNA binding protein in neuronal differentiation. Participation in a collaborative project that examined the role of miRNAs in regulating the expression of nPTB in differentiating muscle cells, sparked my interest in miRNA Biology which was further enhanced in Dr. Sokol’s laboratory in Indiana University where I examined the regulation and functioning of a conserved cluster of three co-transcribed microRNAs in Drosophila. These studies primarily investigated the transcriptional and post-transcriptional regulation of let-7-Complex(let-7-C) microRNAs and the role of these miRNAs during development.
More recently, I shifted my focus towards understanding post-developmental roles of let-7-Complex miRNAs in modulating lifespan and long-term neuronal integrity. In this study, I have identified phase specific roles of let-7 and miR-125 in maintenance of the nervous system during aging. This work has identified the physiological relevance of the targeting of a single mRNA by multiple miRNAs in a scenario where each miRNA exerts a distinct and non-overlapping outcome. More importantly, this study has also identified critical roles for two highly conserved miRNAs in the aging processes that occur in the nervous system. This work formed the basis of my India Alliance fellowship application and moving forward as a Wellcome-DBT intermediate fellow in Regional Centre for Biotechnology, I would like to apply my expertise in RNA biology and model organism genetics towards exploring noncoding RNA mediated mechanisms in dietary restriction and aging. Studies in several model systems have shown that powerful and reproducible interventions like dietary/caloric restriction prolong lifespan predominantly through protein coding mRNAs. Since, non-coding RNAs form greater than 70% of the human genome, my future direction will focus on identifying and evaluating non-coding RNA network components that can be targeted for development of health promoting therapeutic strategies to prolong lifespan and reduce risk factors associated with late onset diseases.