Research

The complexity of life is far greater than what was expected. This complexity arises through extensive regulation at post-transcription level. My lab studies the mechanism of translation regulation of some key transcripts that are important in diseases like diabetes and malaria. The goal of our lab is to understand gene regulation with specific focus on RNA-protein interactions.

Area of Research

Gene regulation: RNA protein interactions

The broad area of my research lab is to understand how specific RNA-protein interactions regulate gene expression. We have elucidated a role for PDI, PABP and HuD in insulin gene expression. We have also recently reported a novel role for PIP4K2A in regulating gene expression in malaria parasite. We have shown that the RNA binding activity of PIP4K is conserved and have also identified specific sequence motif in the RNA that is essential for this interaction.

Translation regulation of insulin

Insulin plays a central role in glucose metabolism in vertebrates and its biosynthesis is regulated by glucose. Major regulation of insulin occurs at the secretion and the protein synthesis level in β-islet cells. These cells contain a large pool of insulin mRNA (10-15% total mRNA), which is translationally quiescent at hypo-glycaemic (<3 mM glucose) conditions. Recruitment to polysomes and activated translation of this mRNA occur in response to higher glucose levels, leading to about 50-fold increase in insulin biosynthesis within an hour. We have delineated the molecular mechanism underlying the glucose stimulated insulin biosynthesis, and have identified specific RNA binding proteins (PDI, PABP, HuD) that associate with insulin mRNA and regulate its biosynthesis. We have previously shown that prolonged exposure of CHO-Glut4 cells (insulin sensitive cells) to insulin results in them becoming insulin resistant. We have delineated the molecular mechanism of this insulin resistance and our results suggest that insulin exposure results in a altered epigenetic regulation leading impaired PI3K/AKT signalling pathways. We have extended these observations to mice and have developed a model of insulin resistance which could be further used for understanding the molecular basis of diabetes and also screen for drugs that alter insulin sensitivity.

Identifying the RNA binding proteins in Plasmodium falciparum

Plasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. During its life cycle, the malarial parasite Plasmodium goes through different asexual stages in human blood, and asexual and sexual stage in mosquito. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that post-transcriptional regulation plays an important role in stage-specific gene expression. We have previously shown that human PIP4K2A from RBC is imported into the parasite and is associated with parasite transcripts. We have shown that the RNA binding activity of PIP4K is conserved as PIP4k from Drosophila, C. elegans and Zebra fish show RNA binding activity. The RNA Binding and kinase function of PIP4K2A may be independent as kinase mutants still show RNA binding activity. Our results suggest that the stem loop structure and the multiple UUGU motif present in the RNA is necessary for the RNA-protein interactions.  to be recognized by PIP4K2A. In order to understand the other targets of PIP4K2A we have performed RNA-Clip experiments followed by sequencing using mammalian cells as we believe that the RNA binding activity of PIP4K2A plays and important role in mammalian gene regulation.

Publications

2021

2020

2019

2018

2017

2016

Before 2016

Current/Past Lab Members

Graduate Students

Naina Gaikwad
Shyam More
Gaurav Agarwal
Sourav Halder

Lab Alumni

Bhavana Muralidharan (2010), Scientist, Instem, Bengaluru, India
Baskar Baktavachalu (2010), Assistant Professor, IIT Mandi, India
Amaresh K. Panda, (2011), Scientist, ILS, Bhubhaneshwar, India
Shardul Kulkarni, (2012), Assistant Research Professor, Pennsylvania, USA
Arya Vindu, (2015), Postdoctoral Fellow, NIH, USA
Abdul Khalique, (2016), Postdoctoral Fellow, NIH, USA
Poonam Pandey, (2016), Associate Scientist, Columbia University, USA
Vishal Dandewad (2018), Postdoctoral Fellow, NIH, USA
Rucha Sarwade, (2019), Postdoctoral Fellow, Monash University, Australia
Shehnaz Bano, (2021), Postdoctoral Fellow, University of Pittsburgh, USA
Jatin Behari, (2021), Postdoctoral Fellow, NUS, Singapore
Pranita Borkar (2022), Postdoctoral Fellow, Texas A&M University