Deepak T. Nair

Deepak T. Nair
Born (1973-10-25) October 25, 1973
Pune, India
Residence Delhi, India
Nationality Indian
Alma mater
Known for Studies on DNA polymerases and RNA polymerases
Awards
Scientific career
Fields
Institutions

Deepak Thankappan Nair (born October 25, 1973) is an Indian Structural Biologist and a scientist at 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 (2008-2013) 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.[1][note 1][2]

Biography

University of Pune

His parents are from the southern state of Kerala and he was born in Pune in the western state of Maharashtra on October 25, 1973,[3] Deepak Nair went to school at the Jai Hind High School (Pimpri) and then later to the St. Vincents Junior College (Pune). He graduated with B.Sc in Chemistry from Fergusson College (1994) and completed his Masters in Biotechnology from the Savitribai Phule Pune University (1996).[4] 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 M. Salunke. Later, he moved to the US to complete his post-doctoral work in the laboratory of Prof. Aneel K. Aggarwal 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 .[5] He worked in NCBS as Reader-F (2007-2013) and Associate Professor (2013-2014). In July, 2014, he joined the Regional Centre for Biotechnology as an Associate professor, a post he holds to date.[4]

Research

Dr. Nair has obtained new insight regarding the molecular mechanisms that determine the fidelity of the replication process in bacteria and flaviviruses. He has discovered the mechanism employed by DNA polymerase IV to rescue replication stalled at damaged nucleotides with unprecedented efficiency and accuracy (Structure, 2014, 23:56-67). Dr. Nair has provided insight into how specialized DNA polymerases that participate in adaptive mutagenesis ensure achieve function (Nucleic Acids Research, 2013, 41:5104-5014; Acta Crystallogr D Biol Crystallogr. 2012 68:960-7, J Nucleic Acids. 2012:285481). His laboratory has shown how GTP binding to the viral RNA-dependent-RNA polymerase ensures accurate initiation of replication of the viral genome (Nucleic Acids Research, 2014, 42:2758-2573). In addition, he has shown that reactive oxygen species do play an important role in the antimicrobial activity of bactericidal antibiotics (Angew Chem Int Ed Engl. 2016 55:2397-400). In collaboration with Prof. D. N. Rao (Department of Biochemistry, IISc), his laboratory has also contributed towards understanding how proteins involved in post-replicative repair of DNA mismatches function (Nucleic Acids Research, 2017, 46:256-266; PLoS One. 2010, 5:e13726)

As a post-doctoral fellow (Dec 2001- July 2007) 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 a variety of 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 are able to synthesize DNA across these lesions and thus prevent the replication fork from stalling. Deepak determined the crystal structure of the catalytic cores of two such polymerases, human DNA polymerase iota (hPolι) and yeast REV1 (yREV1) –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 (Nature, 2004, 430:377; Science, 2005, 309:2219; Structure, 2005, 13:1569; Structure, 2006, 14:749; Nat. Struct. Mol. Biol., 2006, 13:619; Structure, 2008, 16:239; Structure, 2009, 17:530). 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 the determination of the structure of a third Y-family polymerase human DNA Polymerase kappa in its functional state (Mol. Cell, 2007, 25:601). In addition, he also participated in projects aimed at understanding the nature of interactions between the translational regulator Pumilio and non-cognate RNA targets (Structure, 2008, 16:549) and discerning the preference of hPolι for incorporating dGTP when the base of the templating nucleotide is thymine (Structure, 2009, 17:974).

His doctoral thesis (July 1996- Dec 2001) describes the crystallographic analysis of a panel of three murine monoclonal antibodies raised against the same promiscuous peptide antigen PS1 (HQLDPAFGANSTNPD). (J Immunol, 2000, 165:6949; J. Immunol, 2002, 168:2371). 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 (J. Immunol, 2002, 168:2371). He also carried out a computational analysis of the conformational propensities of native and retro-inverso versions of B-cell and T-cell epitopes (J. Immunol, 2003, 170:1362). 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 (J. Biol. Chem., 2001, 276:41377). In addition, he modelled the complex of the ribonuclease restrictocin and its rRNA substrate (Biochemistry, 2001, 40:9115).

Awards and honors

Nair was selected for the Ramanujan Fellowship by the Department of Biotechnology in 2008, the tenure of the fellowship running until 2013,[5] and he became a member of the Guha Research Conference in 2013. He received the National Bioscience Award for Career Development (N-BIOS Prize) in 2014.[6] The Council of Scientific and Industrial Research awarded him the Shanti Swarup Bhatnagar Prize, one of the highest Indian science awards in 2017.[2]

Publications

  • Nirwal S, Kulkarni DS, Sharma A, Rao DN, Nair DT. Mechanism of formation of a toroid around DNA by the mismatch sensor protein. Nucleic Acids Res. 2018 Jan 9;46(1):256-266. doi: 10.1093/nar/gkx1149. PMID 29182773; PMC 5758902.
  • Salunke DM, Nair DT. Macromolecular structures: Quality assessment and biological interpretation. IUBMB Life. 2017 Aug;69(8):563-571. doi: 10.1002/iub.1640. Epub 2017 May 11. Review. PMID 28497559.
  • Kumar A, Gupta C, Nair DT, Salunke DM. MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism. J Biol Chem. 2016 May 20;291(21):11373-84. doi: 10.1074/jbc.M115.699173. Epub 2016 Mar 17. PMID 26987900; PMC 4900281
  • Kottur J, Nair DT. Reactive Oxygen Species Play an Important Role in the Bactericidal Activity of Quinolone Antibiotics. Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2397-400. doi: 10.1002/anie.201509340. Epub 2016 Jan 12. PMID 26757158.
  • Ghodke PP, Gore KR, Harikrishna S, Samanta B, Kottur J, Nair DT, Pradeepkumar PI. The N(2)-Furfuryl-deoxyguanosine Adduct Does Not Alter the Structure of B-DNA. J Org Chem. 2016 Jan 15;81(2):502-11. doi: 10.1021/acs.joc.5b02341. Epub 2016 Jan 4. PMID 26650891.
  • Nair DT, Kottur J, Sharma R. A rescue act: Translesion DNA synthesis past N(2) -deoxyguanosine adducts. IUBMB Life. 2015 Jul;67(7):564-74. doi: 10.1002/iub.1403. Epub 2015 Jul 14. Review. PMID 26173005.
  • Weinert T, Olieric V, Waltersperger S, Panepucci E, Chen L, Zhang H, Zhou D, Rose J, Ebihara A, Kuramitsu S, Li D, Howe N, Schnapp G, Pautsch A, Bargsten K, Prota AE, Surana P, Kottur J, Nair DT, Basilico F, Cecatiello V, Pasqualato S, Boland A, Weichenrieder O, Wang BC, Steinmetz MO, Caffrey M, Wang M. Fast native-SAD phasing for routine macromolecular structure determination. Nat Methods. 2015 Feb;12(2):131-3. doi: 10.1038/nmeth.3211. Epub 2014 Dec 15. Erratum in: Nat Methods. 2015 Jul;12(7):692. PMID 25506719.
  • Kottur J, Sharma A, Gore KR, Narayanan N, Samanta B, Pradeepkumar PI, Nair DT. Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic. Structure. 2015 Jan 6;23(1):56-67. doi: 10.1016/j.str.2014.10.019. Epub 2014 Dec 11. PMID 25497730.
  • Surana P, Satchidanandam V, Nair DT. RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state. Nucleic Acids Res. 2014 Feb;42(4):2758-73. doi: 10.1093/nar/gkt1106. Epub 2013 Nov 28. PMID 24293643; PMC 3936712.
  • Sharma A, Kottur J, Narayanan N, Nair DT. A strategically located serine residue is critical for the mutator activity of DNA polymerase IV from Escherichia coli. Nucleic Acids Res. 2013 May;41(9):5104-14. doi: 10.1093/nar/gkt146. Epub 2013 Mar 21. PMID 23525461; PMC 3643571.
  • Jain D, Nair DT. Spacing between core recognition motifs determines relative orientation of AraR monomers on bipartite operators. Nucleic Acids Res. 2013 Jan 7;41(1):639-47. doi: 10.1093/nar/gks962. Epub 2012 Oct 29. PMID 23109551; PMC 3592433.
  • Sharma A, Subramanian V, Nair DT. The PAD region in the mycobacterial DinB homologue MsPolIV exhibits positional heterogeneity. Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):960-7. doi: 10.1107/S0907444912017623. Epub 2012 Jul 17. PMID 22868761.
  • Sharma A, Nair DT. MsDpo4-a DinB Homolog from Mycobacterium smegmatis-Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches. J Nucleic Acids. 2012;2012:285481. doi: 10.1155/2012/285481. Epub 2012 Mar 15. PMID 22523658; PMC 3317225.
  • Sharma A, Nair DT. Cloning, expression, purification, crystallization and preliminary crystallographic analysis of MsDpo4: a Y-family DNA polymerase from Mycobacterium smegmatis. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Jul 1;67(Pt 7):812-6. doi: 10.1107/S1744309111019063. Epub 2011 Jun 30. PMID 21795801; PMC 3144803.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. DNA synthesis across an abasic lesion by yeast REV1 DNA polymerase. J Mol Biol. 2011 Feb 11;406(1):18-28. doi: 10.1016/j.jmb.2010.12.016. Epub 2010 Dec 15. PMID 21167175; PMC 3127253.
  • Namadurai S, Jain D, Kulkarni DS, Tabib CR, Friedhoff P, Rao DN, Nair DT. The C-terminal domain of the MutL homolog from Neisseria gonorrhoeae forms an inverted homodimer. PLoS One. 2010 Oct 28;5(10):e13726. doi: 10.1371/journal.pone.0013726. PMID 21060849; PMC 2965676.
  • Jain R, Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Replication across template T/U by human DNA polymerase-iota. Structure. 2009 Jul 15;17(7):974-80. doi: 10.1016/j.str.2009.04.011. PMID 19604477; PMC 3030472.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. DNA synthesis across an abasic lesion by human DNA polymerase iota. Structure. 2009 Apr 15;17(4):530-7. doi: 10.1016/j.str.2009.02.015. PMID 19368886; PMC 2703454.
  • Gupta YK, Nair DT, Wharton RP, Aggarwal AK. Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for binding promiscuity. Structure. 2008 Apr;16(4):549-57. doi: 10.1016/j.str.2008.01.006. Epub 2008 Mar 6. PMID 18328718.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Protein-template-directed synthesis across an acrolein-derived DNA adduct by yeast Rev1 DNA polymerase. Structure. 2008 Feb;16(2):239-45. doi: 10.1016/j.str.2007.12.009. PMID 18275815.
  • Lone S, Townson SA, Uljon SN, Johnson RE, Brahma A, Nair DT, Prakash S, Prakash L, Aggarwal AK. Human DNA polymerase kappa encircles DNA: implications for mismatch extension and lesion bypass. Mol Cell. 2007 Feb 23;25(4):601-14. PMID 17317631.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota. Nat Struct Mol Biol. 2006 Jul;13(7):619-25. Epub 2006 Jul 2. PMID 16819516.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. An incoming nucleotide imposes an anti to syn conformational change on the templating purine in the human DNA polymerase-iota active site. Structure. 2006 Apr;14(4):749-55. PMID 16615915.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair. Structure. 2005 Oct;13(10):1569-77. PMID 16216587.
  • Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Rev1 employs a novel mechanism of DNA synthesis using a protein template. Science. 2005 Sep 30;309(5744):2219-22. PMID 16195463.
  • Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004 Jul 15;430(6997):377-80. PMID 15254543.
  • Nair DT, Kaur KJ, Singh K, Mukherjee P, Rajagopal D, George A, Bal V, Rath S, Rao KV, Salunke DM. Mimicry of native peptide antigens by the corresponding retro-inverso analogs is dependent on their intrinsic structure and interaction propensities. J Immunol. 2003 Feb 1;170(3):1362-73. PMID 12538696.
  • Nair DT, Singh K, Siddiqui Z, Nayak BP, Rao KV, Salunke DM. Epitope recognition by diverse antibodies suggests conformational convergence in an antibody response. J Immunol. 2002 Mar 1;168(5):2371-82. PMID 11859128.
  • Jain D, Nair DT, Swaminathan GJ, Abraham EG, Nagaraju J, Salunke DM. Structure of the induced antibacterial protein from tasar silkworm, Antheraea mylitta. Implications to molecular evolution. J Biol Chem. 2001 Nov 2;276(44):41377-82. Epub 2001 Aug 24. PMID 11522783.
  • Nayak SK, Bagga S, Gaur D, Nair DT, Salunke DM, Batra JK. Mechanism of specific target recognition and RNA hydrolysis by ribonucleolytic toxin restrictocin. Biochemistry. 2001 Aug 7;40(31):9115-24. PMID 11478878.
  • Nair DT, Singh K, Sahu N, Rao KV, Salunke DM. Crystal structure of an antibody bound to an immunodominant peptide epitope: novel features in peptide-antibody recognition. J Immunol. 2000 Dec 15;165(12):6949-55. PMID 11120821.

See also

Notes

  1. ↑ Long link - please select award year to see details

References

  1. ↑ "View Bhatnagar Awardees". Shanti Swarup Bhatnagar Prize. 2017. Retrieved November 11, 2017.
  2. 1 2 "10 scientists receive Shanti Swarup Bhatnagar Prize". The Hindu. September 26, 2017. Retrieved 2017-11-11.
  3. ↑ "Brief Profile of the Awardee". Shanti Swarup Bhatnagar Prize. 2017-10-21. Retrieved 2017-10-21.
  4. 1 2 "Biographical Information - Deepak Nair". Regional Centre for Biotechnology. 2017-11-09. Retrieved 2017-11-09.
  5. 1 2 "Profile on SERB" (PDF). Science and Engineering Research Board. 2017-11-14. Retrieved 2017-11-14.
  6. ↑ "N-BIOS Prize 2014" (PDF). Department of Biotechnology. 2014. Retrieved 2017-11-14.
  • "Eureka with Dr Deepak T Nair" (YouTube video). Rajya Sabha TV. November 6, 2017. Retrieved 2017-11-15.
  • "Deepak T Nair on NCBS". National Centre for Biological Sciences. 2017-11-15. Retrieved 2017-11-15.
  • "Deepak T Nair at RCB" http://www.rcb.res.in/deepak
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