Oct 2019 – present, Assistant Professor | SRM University-AP
Nov 2017 - Sep 2019, Postdoctoral researcher | University of California San Francisco (UCSF), USA
Our laboratory is interested in understanding the fascinating biology of bacteria, bacteriophages and their interaction. We are an experimental biology lab and we use a range of approaches including fluorescence microscopy, classical genetics, CRISPR-Cas tools and biochemistry to address our questions. Some of the research areas we are currently focussing are given below.
Uncovering the molecular mechanisms of Bacterial Cell Organization
If we open a bacterial cell and look inside, would we see any organized structures? For a long time, scientists thought that bacterial cells lack internal organization and are mere “bags of free-floating enzymes”. This view, which stemmed from the scarcity of membrane-bounded organelles, has completely changed in recent years. We now know that bacterial cells have an intricate intracellular organization with proteins, mRNAs, and lipids distributed in organized patterns. Thus, bacteria are the inventors of “organization without organelles”. The biological basis for the cellular organization in bacteria is only beginning to be understood. We have previously explored the organization of bacterial cell poles by studying the mechanism of polar targeting of the phosphotransferase system (PTS) in E. coli (Govindarajan S., et al. 2013, Govindarajan S., et al. 2018). We also uncovered the mechanism by which the SecA-dependent secretion system mediates membrane targeting of the bacterial actin homolog, MreB (Govindarajan S., et al. 2017). Currently, we are investigating novel filament-forming proteins in bacteria and uncovering their functions in cell organization.
Understanding the biology of ‘Jumbo-bacteriophages’
Jumbophages are a class of bacterial viruses with exceptionally large (>200 kb) genomes. These phages exhibit a lifestyle that is very distinct from other phages. Two lines of evidence support this view: (a) Jumbophages encode a tubulin-like cytoskeletal protein (PhuZ) which is involved in centring of phage DNA and mediates cargo transport; (b) Jumbophages construct a proteinaceous shell structure, which we have recently shown to be necessary for protecting phage DNA from immune systems like the CRISPR-Cas (Mendoza SD., et al. 2020). Strangely, the jumbophage shell behaves like a eukaryotic nucleus i.e., replication and transcription of phage DNA occur within the shell; phage mRNAs are exported out of the shell for translation; phage proteins, translated by the cytoplasmic ribosomes, are then selectively imported into the shell. How these processes, which are typical of eukaryotes, evolved in a virus is a complete mystery. We are interested in solving some of the mysteries of jumbophages by strategically identifying and studying novel genes that are important for jumbophages life cycle. We foresee that understanding of the life cycle of jumbophages will shed light on how living cells are organized and will improve our ability to use these phages for biotechnological applications (phage therapy, gene delivery, synthetic biology).
Discovery of novel mechanisms of phage-mediated host take-over
Bacteriophages proliferate strictly by exploiting the resources of the host bacterial cell. Several phages encode proteins that inhibit or reprogram host cellular processes in order to take-over. Examples of such processes include modulation or inhibition of host transcription and blockage of the CRISPR-Cas adaptive immune system. We have previously studied the mechanism by jumbo-bacteriophages take-over its host by protecting its genome within a proteinaceous nucleus-like compartment (Mendoza SD., et al. 2020) and the mechanism by which IsrK sRNA of Gifsy-1 prophage of Salmonella interferes with bacterial transcription termination (Hershko-Shalev T., et al. 2016). Currently, we do not know all the host processes that are controlled by phages during lytic or lysogeny infection. Towards this goal, we are interested in discovering new strategies that are employed by phages to take-over bacteria. To start with, we are focussing on E. coli and P. aeruginosa phages that alter the central processes of their respective hosts. Genes responsible for these processes are being identified and characterized. Knowledge gained from these studies will be used for development of novel antibacterial strategies.
Awards & Fellowships
Recipient of ‘Excellence in Ph.D. award’ from the Hebrew University of Jerusalem, Israel, for outstanding PhD thesis
Borges, Adair L., Bardo Castro, Sutharsan Govindarajan, Tina Solvik, Veronica Escalante, and Joseph Bondy-Denomy. Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity. (2020) (Accepted in Nature Microbiology) (Link to preprint) IF-14.3
Mendoza, Senén D., Eliza S. Nieweglowska*, Sutharsan Govindarajan*, Lina M. Leon, Joel D. Berry, Anika Tiwari, Vorrapon Chaikeeratisak, Joe Pogliano, David A. Agard, and Joseph Bondy-Denomy. A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases. Nature 577, no. 7789 (2020): 244-248. (* equal author) (Link) IF-43
Shir Barshishat, Maya Elgrably-Weiss, Jonathan Edelstein, Jens Georg, Sutharsan Govindarajan, Meytal Haviv, Patrick R Wright, Wolfgang R Hess, Shoshy Altuvia*. OxyS small RNA induces cell cycle arrest to allow DNA damage repair. EMBO J. 2017: e201797651. (Link) IF-11.2
Sutharsan Govindarajan*, Nitsan Albocher*, Tamar Szoke, Anat Nussbaum-Shochat, Orna Amster-Choder. Phenotypic heterogeneity in sugar utilization by E. coli is generated by stochastic dispersal of the general PTS protein EI from polar clusters. Frontiers in Microbiology. 2017: p2695. (* equal author) (Link) IF-4.2
Sutharsan Govindarajan# and Orna Amster-Choder#. The bacterial Sec system is required for the organization and function of the MreB cytoskeleton. Plos Genetics. 2017: 13(9): e1007017. (# corresponding author) (Link) IF-5.5
Tal Hershko-Shalev, Ahuva Odenheimer-Bergman, Maya Elgrably-Weiss, Tamar Ben-Zvi, Sutharsan Govindarajan, Hemda Seri, Kai Papenfort, Jörg Vogel and Shoshy Altuvia. Gifsy-1 prophage dual function small and messenger IsrK RNA modulates vital bacterial machineries. Plos Genetics. 2016: 12(4): e1005975. (Link) IF-5.5
Sutharsan Govindarajan*, Yair Elisha*, Keren Nevo-Dinur, Orna Amster-Choder. The general phosphotransferase system proteins localize to sites of strong negative curvature in bacterial cells. mBio. 2013: 4(5) e00443-13. (* equal author) (Link) IF-6.7
Sutharsan Govindarajan and Orna Amster-Choder. Where are things inside a bacterial cell? Current Opinion in Microbiology. 2016. 33(83-90). (Link) IF-6.9
Sutharsan Govindarajan, Keren Nevo-Dinur, Orna Amster-Choder. Compartmentalization and Spatio-Temporal Organization of Macromolecules in Bacteria. FEMS Reviews Microbiology. 2012: 36(5):1005–1022. (Link) IF-11.5
Keren Nevo-Dinur, Sutharsan Govindarajan, Orna Amster-Choder. Subcellular localization of RNA and proteins in prokaryotes. Trends in Genetics. 2012: 28(7):314-22. (Link) IF-10.6
Sutharsan Govindarajan and Orna Amster-Choder. Transcription regulation in bacteria. Reference Module in Biomedical Research. 2014. doi:10.1016/b978-0-12-801238-3.02462-4 (Link)
Evasion tactics manifested by bacteriophages against bacterial immunity. Jenny Y. Zhang*, Sutharsan Govindarajan*, Joseph Bondy-Denomy. (Accepted in ASM book on CRISPR-Cas) (* equal author)
Oral presentation at the ‘ASM Microbe Meeting’, San Francisco, USA (2019)
Oral presentation at the EMBO conference on 'Bacterial morphogenesis, survival and virulence', Kerala, India (2016)
Invited talk at the Department of Molecular Biology and Microbiology, Tufts University, Boston, USA (2015)
Poster presentation at the 5th ASM Conference on Prokaryotic Cell Biology and Development, Washington DC, USA.
Poster presentation at the Boston Bacterial Meeting, Harvard University, MA, USA.
Poster presentation at the 7th ILANIT meeting organized by the Federation of all the Israel Societies for Experimental Biology (FISEB), Eilat, Israel.