I have always been interested in understanding the fundamental cellular processes at the molecular level. Groups of interacting proteins form the basis for the molecular machines that carry out fundamental processes such as DNA replication, transcription, translation etc. An initial understanding of how most biological processes work, therefore, can be gained by knowing how the various proteins interact with each other. We take a combinatorial approach involving biochemical, biophysical and cell biology techniques to address these questions.
Ongoing projects in my group:
- Understanding the molecular architecture of the eukaryotic replisome using budding yeast as a model system
- Understanding the significance of Topoisomerase modulatory proteins in E. coli and Saccharomyces cerevisiae.
- Studying engineered nanomaterial toxicity and its impact on DNA replication process in Saccharomyces cerevisiae
Research Funding:
- DBT-BioCARE (2014-2017, BT/ BioCARE /01/10021/201314)
- FRPDF, Presidency University Kolkata
- DBT-BUILDER grant to the Department of Life Sciences, P.U.
B.Sc: Zoology (Hons.), Chemistry, Physiology (Presidency College, University of Calcutta, 1999)
M.Sc : Biophysics, Molecular Biology and Genetics (University of Calcutta, 2001)
Ph.D: Microbiology and Molecular Biology (Indian Institute of Science, Bangalore, 2008)
Post doctoral training at Paterson Institute for Cancer Research, University of Manchester (2008-2012)
PhD training (2001-2008)
My doctoral thesis work involved identification and characterization of three endogenous inhibitors of an essential bacterial enzyme, DNA gyrase. My studies revealed that all these endogenous inhibitors essentially influence the enzyme activity by sequestering the enzyme away from DNA. None of them cause any cytotoxicity, which usually arises as a result of DNA damage caused by accumulation of gyrase-DNA covalent intermediate. On the contrary they provide protection against such gyrase poisons. Based on these studies, it was proposed that these endogenous proteins exist to serve as cellular defense strategies against external abuse and also modulate the intracellular activity of DNA gyrase as and when required, for accurate division, functioning and survival of the cell.
Postdoctoral training (2008-2012)
After getting my PhD degree in 2008, I joined Paterson Institute for Cancer Research, University of Manchester, England, for my post-doctoral studies. During my tenure, I was trying to understand the molecular composition of the eukaryotic replisome, using budding yeast as a model system. My studies were directed towards understanding how the processivity is achieved in the eukaryotic replisome. I have specifically focused on illustrating the molecular link between the DNA polymerase epsilon and the replicative helicase. I have also investigated the importance of certain unique structural features of MCM helicase. My studies have shown several novel aspects of the eukaryotic replisome which makes it quite distinct and complex from its bacterial counterpart.
Administrative Experience:
- Convener, Departmental Exam Committee
- Convener, Departmental Syllabus Committee
- Departmental Routine Coordinator
- Member, Institutional Biosafety Commitee (IBSC)
- Member, University Committee for students' aid and merit-cum-means scholarship
- Member, University Central Routine Commitee
Research Experience:
The process of DNA replication is central to cell survival and the maintenance of genome integrity. The faithful duplication of the genetic information is an absolute requirement in proliferating cells and this process is known to be defective in many human cancers, explaining the efficacy of traditional cancer treatments that damage DNA or impede dNTP synthesis. Thus, a better understanding of this process is a key part of cancer research, as future cancer therapies could exploit better the inherent replication defects of cancer cells, without being as toxic as traditional treatments. Many important questions in this field still remain unanswered, as the eukaryotic chromosome replication machinery is still poorly characterized. My group focuses on understanding this complex machinery in greater detail. Replisome structure is poorly understood and my postdoctoral work has shown how the leading strand DNA polymerase is associated with the replicative DNA helicase at eukaryotic replication forks. I have identified a unique domain of DNA polymerase epsilon that associates with other replisome components including the ‘GINS’ component of the active DNA helicase. One of the ongoing projects is based on a detailed structure-function analysis of this interaction, using purified recombinant proteins corresponding to the yeast and human orthologues (the orthologues from other species will also be studied if necessary).
We also have had a long-standing interest in understanding the physiological relevance of endogenous proteins that interact and modulate DNA topoisomerases. We are particularly interested in the identification and characterization of novel protein partners of bacterial DNA gyrase and yeast Topoisomerase I. In all these experiments, Escherichia coli and Saccharomyces cerevisiae serve as model organisms.
My preferred areas of teaching include understanding of the fundamental cellular processes like DNA replication, transcription, translation, DNA repair mechanisms and DNA recombination. Based on my research experience, I am also interested in teaching the fundamental principles of cell cycle regulation with special focus on checkpoint controls that exist in order to ensure genome integrity.
Current Teaching Assignments:
- Molecular Biology (UG and PG)
- Recombinant DNA Technology (UG and PG)
- Genetics (UG and PG)
- Biochemistry of Nucleic Acids (UG and PG)
- Functional Proteogenomics (PG)
- PhD Coursework (Training in Molecular Biology techniques)
PhD Students under my guidance:
1. Miss Huma Shaz.(CSIR NET LS) Registered in 2018
Swami Vivekananda Merit-cum-Means Scholarship
Title of thesis: Understanding the importance of Dpb2 during replication in Saccharomyces cerevisiae.
2. Miss Priti Biswas (CSIR NET-SRF) Registered in 2021
Title of thesis: Evaluating the Importance of Endogenous Proteinaceous Interactors of DNA Gyrase in E. coli
3. Mr. Prakash Nandi (UGC NET-JRF) Registered in 2023
Title of thesis: Identification of novel interacting protein partners of Topoisomerase 1 (TOP1) from Saccharomyces cerevisiae.
M.Sc Dissertation Students (Present and Past)
- Amanita Biswas (Jan-July, 2023)
- Poulami Sheet (Jan-July, 2023)
- Sourav Misra (Jan-July 2022)
- Md Arsadullah Ansari (June 2020- May 2021)
- Pujaita Banerjee (July 2020- May 2021)
- Sristi Chakroborty (July 2020- May 2021)
- Somsree Roy (August 2019- May 2020)
- Aaishi Bhattacharya (August 2019- May 2020)
- Raneet Sen (August 2018 - May 2019)
- Shrena Chakraborty (August 2018- May 2019)
- Rahul Baroi (Jan-July, 2018)
- Somnath Ghosal (Jan-July, 2018)
- Nanda Singh (Jan-July, 2016)
- Sabina Khatun (Jan-July, 2015)
- Parej Nath (Jan-July, 2014)
- Chayan Bhattacharya (Jan-July 2013)
Short term Trainee/ Summer Interns (Internal- Present and Past)
- Abhilasha Ghosh (UG-3rd Sem, Since June, 2023-Present)
- Sreelekhsmi R (UG-5th Sem, August, 2023-Nov, 2023)
- Suravi Ghosh (UG-5th Sem, August, 2023-Nov, 2023)
- Arunima Sen (UG-5th Sem, August, 2022-Nov, 2022)
- Prayas Chakrabarty (UG-5th Sem, August, 2022-Nov, 2022)
- Srishti Goswami (UG 6th Sem, April, 2022-June,2022)
- Sarbari Dasgupta (UG 6th Sem, June 2019-August 2019)
- Gaurab Ghosh (UG 3rd year, Jan 2017 to July 2018)
- Najma Parveen (UG 3rd year, June 2017 to July 2018)
- Sukriti Pal (UG 6th Sem, May 2018-July 2018)
Summer Interns (External- Present and Past)
- Rukaiya Gheewala (June-July, 2023, B.Sc student from St. Xavier's College, Kolkata)
- Devhuty Chakrabarty (June-July, 2023, B.Sc student from St. Xavier's College, Kolkata)
- Aishik Sinha (July-August, 2022, B.Sc student from Ramakrishna Mission Vivekananda Centenary College, Rahara)
- Sanchali Ghosh (July-August, 2022, B.Sc student from Institute of Genetic Engineering, Badu)
- Sayantan Das (June-July, 2021, M.Sc student from Dept. of Biophysics and Molecular Biology, Calcutta University)
- Swagata Sen (June-July, 2020, M.Sc student from Dept. of Biophysics and Molecular Biology, Calcutta University)
- Subhashree Mal (May-July, 2018, BS-MS student from IISER, Tirupati)
- Arnadeep Sarkar (June-July, 2016, M.Sc student from Dept. of Biophysics and Molecular Biology, Calcutta University)
Life Member of Indian Association of Biomedical Scientists
- Chakrabarty P, Sen R. & Sengupta, S*. (2023) From parasites to partners: exploring the intricacies of host-transposon dynamics and coevolution. Funct Integr Genomics 23, 278. doi:10.1007/s10142-023-01206-w. Epub ahead of print. PMID: 37610667 [* corresponding author]
- Biswas P, Sengupta S*, Nagaraja V*. (2023) Evolution of YacG to safeguard DNA gyrase from external perturbation. Res Microbiol. Jun 19:104093. doi: 10.1016/j.resmic.2023.104093. Epub ahead of print. PMID: 37343614. [* co-corresponding author]
- Vos SM, Lyubimov AY, Hershey DM, Schoeffler AJ, Sengupta S, Nagaraja V, Berger JM. (2014) Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein. Genes Dev. 28:1485-1497. doi: 10.1101/gad.241984.114. PMID: 24990966
- Sengupta S, van Deursen F, De Piccoli G, Labib K.(2013) Dpb2 Integrates the Leading-Strand DNA Polymerase into the Eukaryotic Replisome. Curr. Biol 23: 543-552. doi: doi: 10.1016/j.cub.2013.02.011.PMID: 23499531
- van Deursen F, Sengupta S, De Piccoli G, Sanchez-Diaz A, Labib K.(2012) Mcm10 associates with the loaded DNA helicase at replication origin and defines a novel step in its activation EMBO J. 31: 2195-2206.doi: 10.1038/emboj.2012.69. PMID: 22433841
- Sengupta S, Ghosh S and Nagaraja V. (2008) Moonlighting function of glutamate racemase from Mycobacterium tuberculosis: racemization and DNA gyrase inhibition are two independent activities of the enzyme. Microbiology. 154: 2796-2803. doi: 10.1099/mic.0.2008/020933-0. PMID: 18757813.
- Sengupta S and Nagaraja V. (2008) YacG from Escherichia coli is a specific endogenous inhibitor of DNA gyrase. Nucleic Acids Res. 36: 4310-4316. doi: 10.1093/nar/gkn355. PMID: 18586829
- Sengupta S and Nagaraja V. (2008) Inhibition of DNA gyrase activity by Mycobacterium smegmatis MurI. FEMS Microbiol Lett. 279: 40-47.doi: 10.1111/j.1574-6968.2007.01005.x. PMID: 18177305.
- Sengupta S, Shah M and Nagaraja V. (2006) Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding. Nucleic Acids Res. 34: 5567-5576.doi: 10.1093/nar/gkl704. PMID: 17020913
- Chatterji M, Sengupta S and Nagaraja V. (2003) Chromosomally encoded gyrase inhibitor GyrI protects Escherichia coli against DNA-damaging agents. Arch. Microbiol. 180: 339-346. doi: 10.1007/s00203-003-0598-4. PMID: 13680098.
Presidency University Students Corner