Center for Cellular and Molecular Biology, Hyderabad
Indian Institute of Technology, Kanpur
Having a biology major throughout my education introduced me to limitless curiosities, from the world of unicellular bacteria, self-sufficient to survive yet forming most intricate colonies, to the multicellular hydra with an extraordinary ability to regenerate; to bees and termites with highly evolved sense of social hierarchy; and ultimately to mouse and man each bearing a bit of the above. I had the benefit of an eclectic training in biology, as an undergraduate I studied microbiology, went on to do a masters in Life Sciences at Pondicherry University, where I was introduced to the cell’s molecular machineries on one hand and amazing balancing acts in ecology on the other. Further a year’s training in Bioinformatics at University of Pune made me familiar with the ever increasing digital data in Biology (it would prove most useful later on). All this led me to take up my doctoral training at Center for Cellular and Molecular Biology (CCMB) Hyderabad.
I was fortunate to work with Dr. Rachel, who was prodding into the shunned but enigmatic world of “junk DNA”, namely the repetitive content of the genome. It was most intriguing to see how by systematic probing and prodding we were able to decipher the almost cryptic functions of these repetitive elements. While others in her group were looking into the Y heterochromatin, I chose to study the Short Interspersed Nuclear Repeats (SINE), namely the Alu’s in human and the B1’s in mouse. Using my earlier training in bioinformatics, along with a generous ounce of imagination and some experimental rigor we postulated that these repetitive elements perhaps were conferring an asymmetry on to the two DNA strands in the form of methylation disparities on otherwise symmetrically methylated CpGs.
At CCMB not only was I a party to animated discussion within our own group but I was also witness to other fascinating investigations in myriad other fields, such as RIPs in Neurospora, boundary elements in Drosophila, apomeosis in Arabidopsis, TSD in Indian mugger, cold adaptation of Arctic bacteria, anthropologic studies on origin of modern man and many many more. A wide exposure as this infused in me a sense of awe, therefore now fortified with training in molecular biology I was eager to explore how cellular and molecular partnerships in a cell were played out at an organism level. This led me to take up the fruit fly, one of the most well characterized and genetically tractable organism as a model system for further studies.
Post PhD I took up a post-doctoral position with Prof. Pradip Sinha at Indian Institute of Technology, Kanpur. His lab was looking into the cellular and development basis of human disease such cancer, both at molecular and systemic levels. Initial years of my investigation into the neoplastic tumor suppressor lethal(2) giant larvae (Lgl) led us to appreciate the developmental basis of tumorigenesis in the developing epithelium of Drosophila. We observed that neoplastic transformation upon an oncogenic lesion entailed a switch in developmental fate from a differentiated to a more primitive cell state. Importantly inhibition of cell fate switch resulted in tumor arrest. This became part of our recent publication (Khan, Bajpai et. al., 2013).
I intuitively knew that what we had uncovered was only the proverbial tip of the iceberg. There were many interesting questions, for instance what triggers the breach in developmental fidelity upon oncogenic loss; how does restoration of development fate arrest tumor progression; does the genome carry many more such “genetic inhibitors” waiting to be explored? The Wellcome-DBT India Alliance Grant came at the most opportune time. I would now use wonderful opportunity provided by the IA Early Career Grant to satiate my curiosity about how a cell manipulates its own developmental history to attain immortality.