Thesis and Guide details:
Details of CSIR Fellowship/ Associateship held, if any or from other sources/ agencies.
Significant foreign assignments:
(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:
Names of the industries in which the technology (ies) has (have) been used :
The achievements already been recognised by Awards by any learned body:
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:
List of Awardee's 10 most significant publications.
List of Awardee's 5 most significant publications during the last 5 years
List of Awardee's 5 most significant publications from out of work done in India
during the last five years:
Complete list of publications in standard refereed journals:
Complete list of publications with foreign collaborators (indicating your status
as author):
List of papers published in Conferences /Symposia/ Seminars, etc:
List of the most outstanding Technical Reports/ Review Articles:
Statement regarding collaboration with scientists abroad:
Total number of patents granted in last five years.
Details of Books published: