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Brief Profile of the Awardee

awardee

Dr Deepak Thankappan Nair

  • 2017
  • Biological Sciences
  • 25/10/1973
  • Structural Biology & Molecular Biology
Award Citation:

Dr Nair has outstanding contributions in providing deep mechanistic insights into the activities of specialized DNA polymerases and accurate initiation of genome replication by viral RNA polymerases.

Academic Qualifications:
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Thesis and Guide details:
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Details of CSIR Fellowship/ Associateship held, if any or from other sources/ agencies.
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Significant foreign assignments:
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(a) Significant contributions to science and/ or technology development by the nominee based on the work done in India during most part of last 5 years:
In response to stress, error-prone DNA polymerases (dPols) are upregulated in bacteria and serve to relieve selection pressure imposed by the maladapted environment. Stress-induced-mutagenesis by these dPols is implicated in the onset of drug resistance in pathogenic bacteria. Using DNA polymerase IV (PolIV) from Escherichia coli and its Mycobacterial homolog (MsDpo4) as model enzymes, Dr. Nair has discovered the unique attributes in these enzymes that allow them to participate in stress-inducedmutagenesis [Nuc. Acids Res. (2013) PMID:23525461; Acta Cryst. D (2012) PMID:22868761; J. Nucleic Acids (2012) PMID:22523658]. He has shown that presence of a polar residue in the active site of PolIV located towards the minor groove of nascent DNA allows controlled mutagenesis to ensure adaptive capability without compromising genetic viability. Also, he has elucidated the mechanism utilized by PolIV to accurately rescue replication stalled at the nitrofurazone (NFZ) derived minor groove DNA adducts and thus neutralize the antimicrobial activity of the NFZ antibiotic [Structure (2014) PMID:25497730; J. Org Chem (2016) PMID:26650891]. These studies show that PolIV can synthesize DNA accurately past damaged nucleotides and in an error-prone manner on undamaged DNA. His laboratory also studies multi-enzyme complexes associated with the replication of the genome of the Japanese Encephalitis Virus and DNA mismatch repair (MMR). He has shown that GTP binding ensures that RNA and nucleotides bind in the right order to guarantee accurate initiation of replication of the flaviviral genome [Nuc. Acids Res. (2014) PMID:24293643]. His laboratory has shed light on the correct assembly of an important enzyme in MMR to ensure calibrated and not adventitious endonuclease activity [PLoS One (2010) PMID:21060849]. He has also shown that minor changes in target DNA sequence of transcription factors have no impact on affinity but lead to drastic changes in the shape of the nucleoprotein complex [Nuc. Acids Res. (2013) PMID:23109551; J. Biol. Chem (2016) PMID:26511320]. Also, he contributed to the development of a new protocol for structure determination using anomalous signal from sulphur atoms [Nat. Methods (2014) PMID:25506719]. Recently, he has unearthed the structural mechanism utilized by PolIV to incorporate oxidized nucleotides in the genome. Based on this mechanism, he has designed and conducted elegant in vivo experiments that ultimately showed that reactive oxygen species do contribute substantially to the antimicrobial activity of bactericidal antibiotics and thus resolved a raging controversy [Angewandte Chemie (2015) PMID:26757158]. Overall, Dr. Nair has utilized structural and biochemical tools coupled with functional in vivo assays to shed new light on bacterial and viral replication. Together, his studies on PolIV show that, to ensure survival of bacteria, this enzyme links increase in stress-induced DNA damage with enhancement in the mutation rate. Additionally, in the presence of ROS, PolIV upregulation results in cell lethality and this caps the contribution of PolIV towards survival of bacteria. Dr. Nair’s contributions allow for development of novel antimicrobials that perturb and accentuate the contributions of PolIV and related orthologs towards survival and lethality, respectively and thus add to the worldwide effort to combat the escalating global problem of antimicrobial resistance.
(b) Impact of the contributions in the field concerned:
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 a novel mechanism to rescue replication stalled at damaged nucleotides, with unprecedented efficiency and accuracy. Dr. Nair has provided insight into how specialized DNA polymerases that participate in adaptive mutagenesis ensure that the mutation frequency is calibrated in the correct range. 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 do play an important role in the antimicrobial activity of bactericidal antibiotics and this contribution has resolved a major controversy regarding antibiotic action. The results obtained in his laboratory provide a platform for the development of novel therapeutic agents against pathogenic bacteria and viral infections. Dr. Nair’s contributions are particularly important because there are no therapeutic drugs available against flaviviral infections and the scourge of antimicrobial resistance represents a global health problem of escalating intensity.
Places where work of last 5 years has been referred/ cited in Books, Reviews:
(i). Paper Cited
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(ii). Book Cited
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Names of the industries in which the technology (ies) has (have) been used :
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The achievements already been recognised by Awards by any learned body:
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The Awardee a fellow of the Indian National Science Academy/Indian Academy of Sciences/National Academy of Sciences/Others:
The Awardee delivered invited lecture(s) in India/abroad and/or chaired any scientific Internatiional Conference Symposium:
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List of Awardee's 10 most significant publications.
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List of Awardee's 5 most significant publications during the last 5 years
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List of Awardee's 5 most significant publications from out of work done in India during the last five years:
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Complete list of publications in standard refereed journals:
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Complete list of publications with foreign collaborators (indicating your status as author):
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List of papers published in Conferences /Symposia/ Seminars, etc:
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List of the most outstanding Technical Reports/ Review Articles:
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Statement regarding collaboration with scientists abroad:
List of Patents taken
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Total number of patents granted in last five years.
Details of Books published:
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Contact Details



  • Regional Centre for Biotechnology
    3rd Milestone Faridabad-Gurgaon Expressway
    Faridabad - 121001
    Haryana INDIA
  • 0129 2848844
  • deepak[at]rcb[dot]res[dot]in
23 Oct 2017, http://ssbprize.gov.in/Content/Detail.aspx?AID=526