Deepak T. Nair
Deepak Thankappan Nair is an Indian Structural Biologist and a scientist at the Regional Centre for Biotechnology. He is known for his studies on DNA and RNA polymerases. Deepak was a Ramanujan fellow of the Science and Engineering Research Board and a recipient of the National BioScience Award for Career Development (Dept of Biotechnology). The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards, for his contributions to biological sciences in 2017. He was inducted as a fellow of the Indian National Science Academy in December 2022. The Haryana government awarded him the Haryana Vigyan Ratna Award for the year 2024.
Biography
His parents are from the southern state of Kerala, and he was born in Pune in the western state of Maharashtra on 25 October 1973. Deepak Nair attended the Jai Hind High School and later went to the St. Vincent's Junior College. He graduated with a BSc in chemistry from Fergusson College and completed his master's in biotechnology from the Savitribai Phule Pune University. Subsequently, he enrolled for his doctoral studies at the National Institute of Immunology, India, to secure a PhD in structural immunology in 2001. For his PhD, he worked under the supervision of Dr. Dinakar Mashnu Salunke. Later, he moved to the US to complete his post-doctoral work in Prof. Aneel K. Aggarwal's laboratory at the Mount Sinai Medical Center. He returned to India in 2007 to take up the position of an independent investigator at the National Centre for Biological Sciences. He worked in NCBS as Reader-F and associate professor. In July 2014, he joined the Regional Centre for Biotechnology as an associate professor and was promoted to professor in July 2019.Research
Deepak Nair has obtained new insight regarding the molecular mechanisms that determine the fidelity of the replication process in bacteria and flaviviruses. Recently, his laboratory contributed towards our understanding of DNA mismatch Repair in prokaryotes. His laboratory has shed new light on the strategy utilized by DNA polymerases to prevent ribonucleotide incorporation. In 2018, his laboratory showed that pyrophosphate hydrolysis is an intrinsic and critical step in the DNA synthesis reaction catalyzed by DNA polymerases, and this discovery was accorded breakthrough status by the journal Nucleic Acids Chemistry. Regarding the piggyBac transposase, his laboratory has shown that the dimerization through the Ring Finger Domain present at the C-terminus attenuates the excision activity of this enzyme. He has discovered the mechanism employed by DNA polymerase IV to rescue replication stalled at damaged nucleotides with unprecedented efficiency and accuracy. Nair has provided insight into how specialized DNA polymerases that participate in adaptive mutagenesis ensure the achievement of function. His laboratory has shown how GTP binding to the viral RNA-dependent-RNA polymerase ensures accurate initiation of replication of the viral genome. In addition, he has shown that reactive oxygen species play an important role in the antimicrobial activity of bactericidal antibiotics. In collaboration with D. N. Rao, his laboratory has also contributed towards understanding how proteins involved in the post-replicative repair of DNA mismatches function. His laboratory has shown that the proofreading domain of the Pfprex DNA polymerase from Plasmodium falciparum is capable of removing misincorporated oxidized nucleotides from the primer and translesion DNA synthesis past common oxidized template nucleotides. Recently, his laboratory has helped characterize a monoclonal antibody that can neutralize different Variants-of-Concern of the SARS-CoV-2 virus. Using computational tools, his laboratory has also identified possible inhibitors of the RNA-dependent-RNA polymerase and proofreading exoribonuclease from SARS-CoV-2. His laboratory also provided the structure of P4A2, a broadly neutralizing anti-SARS-CoV-2 mAb, in complex with the Receptor-Binding-Domain of the Spike protein. So far, he has been centrally involved in the deposition of 76 entries in the protein data bank, a repository of three-dimensional structures of biological macromolecules.As a post-doctoral fellow, he focused on understanding the structural basis of DNA lesion bypass by eukaryotic Y-family DNA polymerases using X-ray crystallography. Due to the action of various agents, lesions are formed on DNA, which interfere with normal replication and may also prove carcinogenic. Eukaryotes possess up to four specialized DNA polymerases that can synthesize DNA across these lesions and thus prevent the replication fork from stalling. Nair determined the crystal structure of the catalytic cores of two such polymerases, human DNA polymerase iota and yeast REV1 –in complex with DNA and incoming nucleotide. The structures of hPolι and yRev1 in complex with undamaged and damaged DNA has shown that these two polymerases prefer altered modes of base-pairing in the active site to facilitate lesion bypass;. Both hPolι and yREV1 have unique active sites that facilitate the formation of non-Watson-Crick base pairs to achieve lesion bypass and rescue stalled replication. He also played a role in determining the structure of a third Y-family polymerase, human DNA Polymerase kappa, in its functional state. In addition, he also participated in projects aimed at understanding the nature of interactions between the translational regulator Pumilio and non-cognate RNA targets and discerning the preference of hPolι for incorporating dGTP when the base of the templating nucleotide is thymine.
His doctoral thesis describes the crystallographic analysis of a panel of three murine monoclonal antibodies raised against the same promiscuous peptide antigen PS1. The comparison of the structure of the antibodies in their bound and unbound state suggests there could be a convergence of both epitope and paratope conformations in an antibody response against a flexible immunodominant epitope. He also carried out a computational analysis of the conformational propensities of native and retro-inverso versions of B-cell and T-cell epitopes. This study showed that conformational and functional mimicry can be achieved through retro-inversion only if the native peptide is present in a linear extended conformation in its functional state. He was also involved in the structure determination of an antibacterial protein from tasar silkworm Antheraea mylitta. In addition, he modeled the complex of the ribonuclease restriction and its rRNA substrate.