Research Area
Structure-function studies on Pore-Forming Toxins and their implications for host-pathogen interaction and immunity.
Research Interests
Pore-forming protein toxins (PFTs) represent a special class of membrane damaging cytolytic proteins, and they are found in wide spectrum of organisms ranging from bacteria to humans. They exert their toxic effects by punching 'holes' into target cell membrane, thus destroying the natural permeability barrier function of the cell membrane. PFTs are, in general, synthesized as water-soluble monomeric molecules, and in contact with target cell membranes they form membrane-inserted oligomeric pores. However, in spite of sharing this overall general scheme, PFTs differ significantly from each other in the intricate details of their pore formation mechanisms. A major mechanistic challenge associated with the membrane pore formation process by PFTs is elucidating the folding pathways that ensure thermodynamic compatibility of the water-soluble monomeric and the membrane-inserted oligomeric form of the toxin with aqueous and lipid milieu, respectively. One of the major research interests of our group is focused on studying structure-function relationship of some of the prominent bacterial PFTs. The critical issues we address are:
1. Mechanistic details of oligomeric membrane pore formation by PFTs.
2. Mechanism(s) associated with cellular responses triggered by PFTs, particularly in the context of host-pathogen interaction processes and immunity.
2023 - 2025 : Editorial Board Member of the Journal of Bacteriology (American Society for Microbiology)
2003 - 2009 : Post-doctoral researcher, Albert Einstein College of Medicine, Bronx, New York, USA
1998 - 2003 : National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal (PhD degree awarded in 2004 by Calcutta University)
1996 - 1998 : MSc in Biochemistry, Calcutta University
2023: Elected as Fellow of Royal Society of Biology, UK.
2021: C. R. Krishna Murti Award Society of Biological Chemists (India) for contributions in the field of Biochemistry and Allied Sciences.
2019: Elected as Fellow of National Academy of Sciences India (NASI) in the year 2019.
2019: Elected as the member of the Guha Research Conference (meeting held in 2018), India.
2015: Recipient of the ‘DBT National BioScience Award for Career Development 2014’.
2015: Recipient of the 'Prof. B.K. Bachhawat International Travel Grant for Young Scientists for the Year 2015'.
2007: Outstanding Post-Doctoral Research Scholar Prize of the Albert Einstein College of Medicine for the year 2007.
2007: Keystone Symposia Travel Scholarship Award for the Lymphocyte Activation and Signaling meeting held on Feb 3 - Feb 8, 2008, in Snowbird, Utah, USA.
Deepinder Kaur, Pratima Verma, Mahendra Singh, Arpita Sharma, Kusum Lata, Arunika Mukhopadhaya and Kausik Chattopadhyay. Pore formation-independent cell death induced by a $\beta$-barrel pore-forming toxin. The FASEB Journal 36(10):e22557, 2022.
Anish Kumar Mondal, Nayanika Sengupta, Mahendra Singh, Rupam Biswas, Kusum Lata, Indrajit Lahiri, Somnath Dutta and Kausik Chattopadhyay. Glu289 residue in the pore-forming motif of Vibrio cholerae cytolysin is important for efficient $\beta$-barrel pore formation. Journal of Biological Chemistry 298(10), 2022.
Nayanika Sengupta, Anish Kumar Mondal, Suman Mishra, Kausik Chattopadhyay and Somnath Dutta. Single-particle cryo-EM reveals conformational variability of the oligomeric VCC $\beta$-barrel pore in a lipid bilayer. Journal of Cell Biology 220(12):e202102035, 2021.
Pratima Verma, Shraddha Gandhi, Kusum Lata and Kausik Chattopadhyay. Pore-forming toxins in infection and immunity. Biochemical Society Transactions 49(1):455–465, 2021.
Anish Kumar Mondal, Paras Verma, Nayanika Sengupta, Somnath Dutta, Shashi Bhushan Pandit and Kausik Chattopadhyay. Tyrosine in the hinge region of the pore-forming motif regulates oligomeric $\beta$-barrel pore formation by Vibrio cholerae cytolysin. Molecular Microbiology 115(4):508–525, 2021.
Reema Kathuria, Anish Kumar Mondal, Rohan Sharma, Samarjit Bhattacharyya and Kausik Chattopadhyay. Revisiting the role of cholesterol in regulating the pore-formation mechanism of Vibrio cholerae cytolysin, a membrane-damaging $\beta$-barrel pore-forming toxin. Biochemical Journal 475(19):3039–3055, 2018.
Nidhi Kundu, Swapnil Tichkule, Shashi Bhushan Pandit and Kausik Chattopadhyay. Disulphide bond restrains the C-terminal region of thermostable direct hemolysin during folding to promote oligomerization. Biochemical Journal 474(2):317–331, 2017.
Anand Kumar Rai and Kausik Chattopadhyay. Revisiting the membrane interaction mechanism of a membrane-damaging $\beta$-barrel pore-forming toxin V ibrio cholerae cytolysin. Molecular microbiology 97(6):1051–1062, 2015.
Anand Kumar Rai and Kausik Chattopadhyay. Trapping of Vibrio cholerae cytolysin in the membrane-bound monomeric state blocks membrane insertion and functional pore formation by the toxin. Journal of Biological Chemistry 289(24):16978–16987, 2014.
Anand Kumar Rai, Karan Paul and Kausik Chattopadhyay. Functional mapping of the lectin activity site on the $\beta$-prism domain of Vibrio cholerae cytolysin: implications for the membrane pore-formation mechanism of the toxin. Journal of Biological Chemistry 288(3):1665–1673, 2013.