Department of
Chemistry

S.G. Srivatsan obtained his M. Sc. degree in chemistry from Indian Institute of Technology, Madras in 1995 and PhD in bioorganic chemistry from Indian Institute of Technology, Kanpur in 2003. He was an Alexander von Humboldt postdoctoral fellow at University of Bonn, Germany and a postdoctoral fellow at University of California, San Diego before joining IISER Pune in November 2008.

Research 

Chemical Biology: Nucleic Acid Chemistry and Biophysics

My group is developing tools to assess structure, dynamics and function of nucleic acids in cell-free and cellular environments. We have initiated a research program to develop structurally non-perturbing and conformation-sensitive multifunctional nucleoside probes for studying nucleic acids in real time by fluorescence, in 3D by X-ray crystallography and in cells by NMR. Some of these nucleoside analogs have been utilized in developing assays to (i) detect nucleic acid damage (depurinated site) in DNA and RNA, (ii) monitor nucleic acid-drug binding and (iii) study the structure and recognition properties of non-canonical nucleic acid structures such as G-quadruplexes and i-motifs. We are also developing new chemo-enzymatic methods to functionalize nucleic acids by using bioorthogonal chemistry. We have developed practical chemical labeling and imaging techniques for cellular RNAs by using novel toolbox made of azide- and alkyne-modified UTP analogues. These analogues are readily incorporated into transcribing RNA by endogenous RNA polymerases, which can be posttranscriptionally labeled with a variety of probes by bioorthogonal reactions such as click and Staudinger ligation reactions. Taking forward this methodology we have recently remodeled CRISPR guide RNA by using a terminal nucleotide transferase to display small molecules on specific gene targets.

Selected Publications

George, J.T., and Srivatsan, S. G.* 2020. Responsive fluorescent nucleotides serve as efficient substrates to probe terminal uridylyl transferase. Chem. Commun. 56: 12319−12322.

George, J.T., Mohd. Azhar, Aich, M., Sinha, D., Ambi, U. B., Maiti, S.,* Chakraborty, D.,* and Srivatsan, S. G.* 2020. Terminal uridylyl transferase mediated site-directed access to clickable chromatin employing CRISPR-dCas9. J. Am. Chem. Soc. 142: 13954−13965.

Ashok, N., Ishtiyaq, A., Saddam, Y.K., Kayarat, S.,* and Srivatsan, S. G.* 2019. Probing G-quadruplex topologies and recognition concurrently in real time and 3D using a dual-app nucleoside probe. Nucl. Acid. Res. 47: 6059–6072.

Manna, S., Sarkar, D., and Srivatsan, S. G.* 2018. A Dual-app nucleoside probe provides structural insights into the human telomeric overhang in live cells. J. Am. Chem. Soc. 140: 12622–12633.

Nuthanakanti, A., Boerneke, M.A., Hermann, T. and Srivatsan S. G. 2017. Structure of the ribosomal decoding site RNA containing a Se-modified responsive fluorescent ribonucleoside probe. Angewandte Chemie International Edition 56: 2640–2644.

Sawant, A.A., Tanpure, A.A., Mukherjee, P.P., Athavale, S., Kelkar, A., Galande, S. and Srivatsan, S.G. 2016. A versatile toolbox for posttranscriptional chemical labeling and imaging of RNA. Nucleic Acids Research 44: e16.

Tanpure, A.A. and Srivatsan, S.G. 2015. Conformation-sensitive nucleoside analogues as topology-specific fluorescence turn-on probes for DNA and RNA G-quadruplexes. Nucleic Acids Research 43: e149.

Rao, H., Tanpure, A.A., Sawant, A.A. and Srivatsan, S.G. 2012. Enzymatic incorporation of an azide-modified UTP analog into oligoribonucleotides for post-transcriptional chemical functionalization. Nature Protocols 7: 1097–1112.