Contact
Biography
I completed my PhD from University of Cambridge in Biophysical Chemistry and continued as a Sir Henry Wellcome Postdoctoral Fellow between University of Cambridge, UK; University of Bonn, Germany and Yale University, USA. During this appointment, I have been independently leading my international research programme with leading experts in RNA-protein biochemistry and structural biology. As an Anne McLaren Fellow at University of Nottingham, I will be pioneering the study of structure and dynamics of RNP complexes at the Vet School and will be contributing towards development of new Research Ecosystems focussed on structural investigations of functionally important RNA-protein systems in health and diseases.
Expertise Summary
My research interests lie in understanding the role of non-coding, regulatory RNAs and their complexes in cellular health and disease progression, particularly during HIV infection. Towards this, I have developed a niche in combining experimental biochemical techniques and theoretical biophysics to characterise the structure, dynamics and function of RNA-protein complexes at atomic resolution. The techniques I use include heterologous protein expressions, cell culture, protein and RNA biochemistry, electron microscopy, NMR spectroscopy, X-ray crystallography and molecular dynamics simulations.
Research Summary
As a Anne McLaren Fellow, I am keen on understanding the impact of host-pathogen ncRNP complexes on HIV pathogenesis and have a long-term vision to construct a high-resolution, dynamic… read more
Recent Publications
BORKAR, ADITI N, VALLURUPALLI, PRAMODH, CAMILLONI, CARLO, KAY, LEWIS E and VENDRUSCOLO, MICHELE, 2017. Simultaneous NMR characterisation of multiple minima in the free energy landscape of an RNA UUCG tetraloop: Physical Chemistry Chemical Physics Physical Chemistry Chemical Physics. 4, 1-8 BORKAR, ADITI N, BARDARO, MICHAEL F, CAMILLONI, CARLO, APRILE, FRANCESCO A, VARANI, GABRIELE and VENDRUSCOLO, MICHELE, 2016. Structure of a low-population binding intermediate in protein-RNA recognition.: Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America. 113(26), 7171-7176
Current Research
As a Anne McLaren Fellow, I am keen on understanding the impact of host-pathogen ncRNP complexes on HIV pathogenesis and have a long-term vision to construct a high-resolution, dynamic structure-function interactome of regulatory RNAs to aid global health challenges. Specifically, I will use an integrated structural biology approach to investigate the role of the biochemically well characterised HIV TAR RNA element and Tat protein in transcription activation and translation initiation of HIV mRNA by determining high-resolution structures of the Transactivation Complex, the 7SK RNP Complex and the Pre-Initiation Complex.
Past Research
My research interests lie in understanding the role of non-coding, regulatory RNAs and their complexes in cellular health and disease progression, particularly during HIV infection. Towards this, I have developed a niche in combining experimental biochemical techniques and theoretical biophysics to characterise the structure, dynamics and function of RNA-protein complexes at atomic resolution.During my doctoral work with Professor Michele Vendruscolo and Professor Chris Dobson at University of Camrbridge, UK, I combined NMR spectroscopy with Molecular Dynamics simulations to determine the first high-resolution structure of an intermediate state populated during HIV TAR:Tat RNP recognition. Next, as a Sir Henry Wellcome Postdoctoral Fellow with Professors Matthais Geyer (University of Bonn, Germany) and Tom Steitz (Yale University USA; 2009 Nobel Prize in Chemistry for discovery of the structure of the ribosome), I investigated the interactions of this RNP complex with human proteins using a combination of experimental biochemistry and theoretical biophysics techniques. I also developed a novel technique called 'RHyTEM' for solid phase enrichment of native RNP complexes directly suited for transmission electron microscopy to allow structure determination of such challenging systems.
Future Research
Recently, many cellular ncRNAs have been identified that contribute significantly to the HIV virus-host interplay in humans. For example, NRON targets Tat for proteasomal degradation and thus regulates HIV latency. However, such native complexes are typically large, multi-subunit, dynamic and short-lived systems and thus are not directly amenable for conventional structure determination methods. To address this challenge, I recently developed the 'RHyTEM' technique (currently exploring Intellectual Property Rights protection and commercialization) that allows solid phase enrichment of native RNP complexes from cell lysates directly suited for single particle EM. Thus, my first goal after the NRF would be to use RHyTEM for both well-characterised and novel players in HIV pathogenesis and build their interactome to gain new structure-function insights. This study will be the first step towards constructing a comprehensive, high-resolution structural interactome of RNP complexes involved in HIV pathogenesis. Next, I am also keen on extending this approach towards other (re-)emerging infectious diseases, such as Zika and Ebola, to identify common links underlying viral pathogenesis and further towards diseases with high global burden, such as neurodegeneration and cancer, to understand their molecular physiology and open novel avenues for development of diagnostic, therapeutic and preventive strategies. Towards this, during the course of the fellowship, I also plan to initiate collaborations with local, national and international experts on transcriptomics and cell biology of infection and cell malfunction