VIT University, Vellore, Tamilnadu, India
Department of Microbiology and Cell Biology, IISc, Bangalore
Centre for Infectious Disease Research (CIDR), IISc Bangalore
My interest in biology was seeded early right from high school and my interest in the basic unit of life, pathology and disease, led me to opt for a more specialized subject (biotechnology) for my graduation. As a part of B.Tech final year dissertation, I enjoyed studying the impact of somatic mutations in PIK3CA and XRCC1 genes in breast tumors among Indian women. These studies determined the underlying relationship between the genetic mutations and its phenotypic effects1.
My dissertation work fueled my desire for higher studies and a career in biological research. With this idea in mind, I joined Dr. Pravir Kumar’s group for my integrated PhD at VIT University. Here the laboratory was focused on studying role of chaperons in hypoxia and neurodegenerative disorder. Since hypoxia and angiogenesis are one of the hallmarks of cancer progression, my work was aimed to screen and characterize the mechanisms of anti-angiogenic compounds. In this regard, I successfully generated mice models of experimental tumors and exploring the mechanisms of action upon treatment with various diet-derived compound in vitro and in vivo. Here we identified three commercially available flavonoids having anti-angiogenic effect alone/or in combination. These biomolecules regulate various proteins responsible for angiogenesis, hypoxia, proliferation and apoptosis, including heat shock protein2,3. Our findings put forward a plausible clinical application of these diet-derived compounds, as both angio-inhibitory and anti-tumor. I was instrumental in several other ongoing projects in the lab which expanded my knowledge further in other fields of research such as neurodegenerative disease and the functional role of various protective molecules4,5,6. Importantly, I established productive collaborations with scientists working in the area of angiogenesis and cancer to enrich my understanding of cancer pathogenesis.
Because of my training in cancer pathogenesis, I developed a proposal on understanding the mechanism of BCL6 translocation in Diffuse Large B-cell Lymphoma (DLBL) and received the prestigious DS-Kothari-postdoctoral fellowship under the supervision of Dr. S.C. Raghavan (Biochemistry department, IISc Bangalore).
During my brief stint in the laboratory of Dr. Raghavan, I was involved in studying the mechanism of BCL6 translocation in DLBL and DNA repair mechanism in heart. In this project, based on available sequencing data from DLBL patients, we observed that most of the breakpoints were located at the 5’UTR of BCL6 gene. Our in- silico, biochemical and biophysical results indicated for the first time, formation of non-B-DNA (G- quadruplex) structure in 5’UTR of BCL6 breakpoint region. Altogether, this position helps me to expand my knowledge in field of DNA secondary structure and gain expertise in various biophysical and biochemical assays. During this time, I was always intrigued about the fact that although much is known about the role of G-quadruplex in the field of cancer, there was very little information available about their roles in other disease conditions. In this regard, I was always interested to study the role of these structures in those organisms, which have high GC content. This led me to explore the role of these structures in Mycobacterium tuberculosis (Mtb) whose average GC content (~ 67%) is higher than other bacteria. Also, similar to tumors, tuberculosis granulomas are also hypoxic, and bacteria within the granulomas remain tolerant to drugs and eventually acquire drug resistance. Interestingly, the role of G-quadruplex in these processes remains unexplored. To acquire knowledge about TB pathogen, I joined Microbiology and Cell Biology Department, IISc under the DBT-IISc partnership program. Here, I gained new knowledge about Mtb biology and learnt several new techniques (creation of gene knock-outs, macrophage infections, and animal models of TB). I was trained to work inside the biosafety level III (BSL-III) environment. Overall my PhD and post-doctoral experience provided me with diverse opportunities to present and exchange my ideas at various national and international platforms. I applied to Wellcome/DBT India Alliance Early career fellowship to explore the association between Mtb biology and G- quadruplex.
In my opinion, Early Career Fellowship funded by Welcome Trust/DBT India Alliance provide an excellent opportunity for any young scientist to develop their scientific career and spruce themself to work independently. The basis of an independent scientific career is formed by knowledge, training and experience to troubleshoot problems and plan ahead with the challenging problems in mind. This fellowship will provide them an opportunity to expand their current skill set, broaden their horizon and offers a stage for transiting into cross- disciplinary areas. From the initial stage of the application to final selection, this fellowship grooms the applicant to meet the international standards in term of identifying relevant cutting age research problems in life science, supervisor, mentor and collaborator. In addition, this fellowship will allow the guidance of supervisor and mentor right from the beginning which would be essential for them to focus on given problem and build the required skill to grow as an independent researcher. Further, this fellowship will grant them the opportunity to explore the research environment in different labs within and outside the country, where they can take up work to address their research problems with a clear idea of the availability of facilities and infrastructure for the same. Moreover, the extensive support in term of flexible funding, and personal support provided by Wellcome Trust/DBT India Alliance, allows researchers to procure consumables and reagents with great ease.
The national and international research collaborations with eminent scientists will be crucial to gain new insight in addressing the proposed research. A prestigious fellowship such as this one would give them access to work with specialists from different fields and help them to improve their knowledge in diverse fields. I trust this fellowship (Wellcome Trust/DBT India Alliance Fellowship) will help young scientist to broaden their scientific maturity and research experience by gaining exposure to diverse research environments.