Dr. Indrajit Lahiri
Assistant Professor, Biological Sciences

Email:   ilahiri(AT)iisermohali.ac.in

Phone:  +91 172 2293145

Fax:      +91 172 2240266

Personal Page:  Lahiri Lab

 

Research Area
 Molecular Mechanism of DNA replication

Research Focus

DNA replication forms the basis of life. We are interested to understand how the macromolecular machinery  performing replication (i.e. the “replisome”) functions. While we know quite a bit about how the individual protein   components of the replisome work, how these proteins come together and catalyze replication as a whole is less   clear. On the other hand, these macromolecular interactions are essential for modulating different aspects of   replication such that genome duplication can occur in co-ordination with other cellular processes.   

We are currently focusing our efforts to understand the molecular mechanism of replication in the organelle called   “apicoplast”. Apicoplasts are non-photosynthetic plastidsessential for the viability of pathogenic eukaryotes such   as  Plasmodium and Toxoplasma,causative agents of infectious diseases like malaria and toxoplasmosis. The   apicoplast replicates and maintains its own organellar genome by recruiting and assembling a specialized   machinery for this sole purpose. The essential nature of this organelle in the context of a pathogen presents   apicoplast replication as a potential target for drug development that could help address growing concerns over   the emergence drug-resistant pathogenic strains worldwide. However, at present we know very little about how this    molecular machine works. Using transient state enzyme kinetics, next-generation DNA sequencing and single   particle cryo-electron microscopy we are trying to decipher the molecular mechanism of the apicoplast replisome   and its implications in the larger context of pathogenesis.   


Selected Publications

  • Lahiri I, Xu J, Han BG, Oh J, Wang D, DiMaio F, Leschziner AE. (2019) 3.1Å structure of yeast RNA polymerase II elongation complex stalled at a cyclobutane pyrimidine dimer lesion solved using streptavidin affinity grids. JSB. (in press; https://doi.org/10.1016/j.jsb.2019.06.004)
  • Cianfrocco MA, Lahiri I, DiMaio F, Leschziner AE. (2018) cryoem-cloud-tools: A software platform to deploy and manage cryo-EM jobs in the cloud. JSB. 203(3):230-35.
  • Xu J*, Lahiri I*, Wang W, Wier A, Cianfrocco MA, Chong J, Hare A, Dervan PB, DiMaio F, Leschziner AE, Wang D. (2017) Structural Basis for Eukaryotic Transcription-Coupled DNA Repair Initiation. Nature. 551(7682):653-57.
  • Mukherjee P*, Wilson RC*, Lahiri I, Pata JD. (2014) Three residues of the interdomain linker determine the conformation and single-base deletion fidelity of Y-family translesion polymerases. J Biol Chem. 289(10):6323-31.
  • Lahiri I*, Mukherjee P*, Pata JD. (2013) Kinetic Characterization of Exonuclease-Deficient Staphylococcus aureus PolC, a C-family Replicative DNA Polymerase. PLoS ONE. 8(5): e63489.
  • Mukherjee P*, Lahiri I*, Pata JD. (2013) Human polymerase kappa uses a template-slippage deletion mechanism, but can realign the slipped strands to favour base substitution mutations over deletions. Nucleic Acids Res. 41(9):5024-35.
  • Agrawal RK, Sharma MR, Yassin A, Lahiri I and Spremulli LL. (2011) Structure and function of organellar ribosomes as revealed by cryo-EM. In Ribosomes: Structure, Function, and Dynamics, Rodnina M, Wintermeyer W, and Green R eds. (SpringerWien, New York), pp. 83-96.

* Equal contribution author.