Welcome to DUTTA Cryo-EM Lab
Cryo-EM Structural Biology lab
My group is focusing on the structural studies of non-ribosomal peptide synthase, pore-forming toxins, bacterial secretion systems, bacterial ion channels, and GPCRs using cryo-electron microscopy. Single-particle cryo-electron microscopy (cryo-EM) techniques are developing rapidly for the structural characterization of complicated biological complexes. These methods generate snapshots of macromolecules in solution and under highly controlled biochemical environments, a crucial condition for probing physiological structures of distinct functional states. Recent high-impact publications suggest that cryo-EM has enough potential to resolve the high-resolution structure of biological samples and is an essential structural biology instrument, which allows us to determine the three-dimensional (3D) structures of large biological macromolecules, macromolecular complexes, and cell components We use different biochemical, biophysical techniques including negative staining electron microscopy and cryo-EM techniques to characterize the conformational dynamics of very small (100 kDa) protein complexes to very large biological macromolecules (2.6 MDa).
RESEARCH INTEREST
1. Metabolic pathways of Mycobacterium tuberculosis
2. Pore-forming toxins and host–pathogen interaction
3. Bacterial secretion systems to understand the secretion of virulence factors.
Structural and functional characterization of the metabolic pathways of Pathogenic bacteria
Mycobacterium tuberculosis (Mtb) is the causative agent of one of the deadliest infectious diseases known to man, tuberculosis. Mtb has a remarkable ability to persist inside the oxidatively hostile environment of human phagocytes encountering Reactive Oxygen Species, Reactive Nitrogen Species, low pH and nutrient starvation etc. This remarkable ability of Mtb made it a successful human pathogen. There are certain products generated from different metabolic pathways of Mtb helps it to combat hostile environment inside human. We are interested to know the mechanism as well as the structural details of proteins present in these kinds of the metabolic pathway.
PUBLICATIONS
Research Publications in International Journals 2016-2020 (Assistant Professor)
Cryo-EM reveals the membrane-binding phenomenon of EspB, a virulence factor of the Mycobacterial Type VII secretion system. Sengupta N, P S, Dutta S. J Biol Chem. 2023 Mar 6:104589. doi: 10.1016/j.jbc.2023.104589. Epub ahead of print. PMID: 36889587.
Cryo-EM-based structural insights into supramolecular assemblies of γ-hemolysin from S. aureus reveal the pore formation mechanism. Mishra S, Roy A, Dutta S. Structure. 2023 Mar 27:S0969-2126(23)00085-0. doi: 10.1016/j.str.2023.03.009.
Glu289 residue in the pore-forming motif of Vibrio cholerae cytolysin is important for efficient b-barrel pore formation. Mondal AK, Sengupta N, Singh M, Biswas R, Lata K, Lahiri I, Dutta S, Chattopadhyay K. J Biol Chem. 2022 Aug 30:102441. doi: 10.1016/j.jbc.2022.102441.
Structural insights into thermostable direct hemolysin of Vibrio parahaemolyticus using single-particle cryo-EM. Mishra S, Kundu N, Pramanick I, Kumar A, Chattopadhyay K, Dutta S. Proteins. 2023 Feb;91(2):137-146. doi: 10.1002/prot.26416. Epub 2022 Sep 8.
S-Adenosylmethionine-responsive cystathionine β-synthase modulates sulfur metabolism and redox balance in Mycobacterium tuberculosis. Bandyopadhyay P, Pramanick I, Biswas R, Ps S, Sreedharan S, Singh S, Rajmani RS, Laxman S, Dutta S, Singh A.Sci Adv. 2022 Jun 24;8(25):eabo0097. doi: 10.1126/sciadv.abo0097. Epub 2022 Jun 24.PMID: 35749503.
User-friendly, High-throughput, and Fully Automated Data Acquisition Software for Single-particle Cryo-electron Microscopy. Kumar A, P S, Gulati S, Dutta S.J Vis Exp. 2021 Jul 29;(173). doi: 10.3791/62832.PMID: 34398142
Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer. Sengupta N, Mondal AK, Mishra S, Chattopadhyay K, Dutta S. J Cell Biol. 2021 Dec 6;220(12):e202102035. doi: 10.1083/jcb.202102035. Epub 2021 Oct
Conformational flexibility and structural variability of SARS-CoV2 S protein. Pramanick I, Sengupta N, Mishra S, Pandey S, Girish N, Das A, Dutta S. Structure. 2021 Apr 26:S0969-2126(21)00122-2. doi: 10.1016/j.str.2021.04.006. Online ahead of print.PMID: 33932324.
A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein. Khatri B, Pramanick I, Malladi SK, Rajmani RS, Kumar S, Ghosh P, Sengupta N, Rahisuddin R, Kumar N, Kumaran S, Ringe RP, Varadarajan R, Dutta S, Chatterjee J. Nat Chem Biol. 2022 Jun 2. doi: 10.1038/s41589-022-01060-0. Epub ahead of print. PMID: 35654847.
Simplified Approach for Preparing Graphene Oxide TEM Grids for Stained and Vitrified Biomolecules. Kumar A, Sengupta N, Dutta S.Nanomaterials (Basel). 2021 Mar 5;11(3):643. doi: 10.3390/nano11030643.
Multiple nanocages of a cyanophage small heat shock protein with icosahedral and octahedral symmetries. Biswas S, Garg P, Dutta S, Suguna K.Sci Rep. 2021 Oct 25;11(1):21023. doi: 10.1038/s41598-021-00172-2.PMID: 34697325
Malladi SK, Singh R, Pandey S, Gayathri S, Kanjo K, Ahmed S, Khan MS, Kalita P, Girish N, Upadhyaya A, Reddy P, Pramanick I, Bhasin M, Mani S, Bhattacharyya S, Joseph J, Thankamani K, Raj VS, Dutta S, Singh R, Nadig G, Varadarajan R. Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment. J Biol Chem. 2020 Nov 5:jbc.RA120.016284. doi: 10.1074/jbc.RA120.016284.
Protective Efficacy of Recombinant Influenza Hemagglutinin Ectodomain Fusions. Mittal N, Sengupta N, Malladi SK, Reddy P, Bhat M, Rajmani RS, Sedeyn K, Saelens X, Dutta S, Varadarajan R.Viruses. 2021 Aug 27;13(9):1710. doi: 10.3390/v13091710.PMID: 34578291
N-Terminal Region of Vibrio parahemolyticus Thermostable Direct Hemolysin Regulates the Membrane-Damaging Action of the Toxin. Kundu N, Verma P, Kumar A, Dhar V, Dutta S, Chattopadhyay K.Biochemistry. 2020 Feb 4;59(4):605-614. doi: 10.1021/acs.biochem.9b00937. Epub 2019 Dec 20.
Tyrosine in the hinge region of the pore-forming motif regulates oligomeric β-barrel pore formation by Vibrio cholerae cytolysin. Mondal AK, Verma P, Sengupta N, Dutta S, Bhushan Pandit S, Chattopadhyay K.Mol Microbiol. 2020 Oct 21. doi: 10.1111/mmi.14631. Online ahead of print.
Malladia SK, Schreiberb D, Pramanicka I, Sridevia MA, Goldenzweigb A, Dutta S, Fleishman SJ, Varadarajan R. One-step sequence and structure-guided optimization of HIV-1 envelope gp140. Current Research in Structural Biology. 2020 Volume 2, Pages 45-55. https://doi.org/10.1016/j.crstbi.2020.04.001.
Kundu N ,Verma P ,Kumar A , Dhar V, Dutta S, Chattopadhyay K, N-Terminal Region of Vibrio parahemolyticus Thermostable Direct Hemolysin Regulates the Membrane-Damaging Action of the Toxin. Biochemistry. 2020 Feb 4;59(4):605-614. doi: 10.1021/acs.biochem.9b00937.
Ghosh E, Dwivedi H, Baidya M, Srivastava A, Kumari P, Stepniewski T, Kim HR, Lee MH, van Gastel J, Chaturvedi M, Roy D, Pandey S, Maharana J, Guixà-González R, Luttrell LM, Chung KY, Dutta S, Selent J, Shukla AK. Conformational Sensors and Domain Swapping Reveal Structural and Functional Differences between β-Arrestin Isoforms. Cell Rep. 2019 Sep 24;28(13):3287-3299.e6. doi: 10.1016/j.celrep.2019.08.053
Datta M, Aroli S, Karmakar K, Dutta S, Chakravortty D, Varshney U. Development of mCherry tagged UdgX as a highly sensitive molecular probe for specific detection of uracils in DNA. Biochem Biophys Res Commun. 2019 Oct 8;518(1):38-43. doi: 10.1016/j.bbrc.2019.08.005. Epub 2019 Aug 9.
Koehl A, Hu H, Feng D, Sun B, Zhang Y, Robertson MJ, Chu M, Kobilka TS, Laermans T, Steyaert J, Tarrasch J, Dutta S, Fonseca R, Weis WI, Mathiesen JM, Skiniotis G, Kobilka BK. Structural insights into the activation of metabotropic glutamate receptors. Nature. 2019 Feb;566(7742):79-84.
Bhandari S, Biswas S, Chaudhary A, Dutta S, Suguna K. Dodecameric structure of a small heat shock protein from Mycobacterium marinum M. Proteins. 2019 Jan 11. doi: 10.1002/prot.25657.
Kumar S, Panda H, Makhdoomi MA, Mishra N, Safdari HA, Chawla H, Aggarwal H, Reddy ES, Lodha R, Kumar Kabra S, Chandele A, Dutta S, Luthra K. An HIV-1 broadly neutralizing antibody from a clade C infected pediatric elite neutralizer potently neutralizes the contemporaneous and autologous evolving viruses. J Virol. 2018 Nov 14. pii: JVI.01495-18. doi: 10.1128/JVI.01495-18.
Safdari, HA, Pandey, S, Shukla, AK, Dutta, S. Illuminating GPCR Signaling by Cryo-EM. Trends Cell Biol, 2018, 28, 591-594. (Corresponding Author).
Kesavardhana S, Das R, Datta CM, Ecto R, Srilatha L, DiStefano NS, Swoyer RD, Joyce JG, Dutta S et al. Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies. J Biol Chem, 2017, 292, 278-291.
Research Publications in International Journals 2010-2016 (Ph.D. & Postdoctoral Fellow)
Yee A, Oleskie AN, Dosey AM, Kretz CA, Gildersleeve RD, Dutta S, Su M, Ginsburg D, Skiniotis G. Visualization of an N-terminal fragment of von Willebrand factor in complex with factor VIII. Blood. 2015, 126:939-42.
Xu K, Chan YP, Bradel-Tretheway B, Akyol-Ataman Z, Zhu Y, Dutta S, Yan L, Feng Y, Wang LF, Skiniotis G, Lee B, Zhou ZH, Broder CC, Aguilar HC, Nikolov DB. PLoS Pathog. Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly. 2015 8;11(12).
Dutta, S.*, Whicher, J. R.*, Hansen, D. A., Hale, W. A., Chemler, J. A., Congdon, G. R., Narayan, A. R., Håkansson, K., Sherman, D. H., Smith, J. L., and Skiniotis, G. Structure of a modular polyketide synthase. Nature. 2014, 510:512-17. [*Equal contribution].
Whicher, J. R.*, Dutta, S.*, Hansen, D. A., Hale, W. A., Chemler, J. A., Congdon, G. R., Narayan, A. R., Håkansson, K., Sherman, D. H., Smith, J. L., and Skiniotis, G. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature. 2014, 510:560-64. [*Equal contribution].
Akey DL, Brown WC, Dutta S, Konwerski J, Jose J, Jurkiw TJ, DelProposto J, Ogata CM, Skiniotis G, Kuhn RJ, Smith JL. Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. Science. 2014, 343 :881-85.
Dutta, S, Banerjee, KK, Ghosh AN. Cryo-electron microscopy reveals the membrane insertion mechanism of V. cholerae hemolysin. J Biomol Struct Dyn. 2013, 32:1434-42.
Lyon, A.M., Dutta, S., Skiniotis, G., and Tesmer, J.J.G. Characterization of phospholipase C-β3 complexes by X-ray crystallography and single particle cryo-electron microscopy. Transactions of the American Crystallographic Association (2013).
Lyon AM, Dutta S, Boguth CA, Skiniotis G, Tesmer JJ. Full-length Gα(q)-phospholipase C-β3 structure reveals interfaces of the C-terminal coiled-coil domain. Nat Struct Mol Biol. 2013, 20(3):355-62.
Chan YP, Lu M, Dutta S, Yan L, Barr J, Flora M, Feng YR, Xu K, Nikolov DB, Wang LF, Skiniotis G, Broder CC. Biochemical, conformational, and immunogenic analysis of soluble trimeric forms of henipavirus fusion glycoproteins. J Virol. 2012, 86(21):11457-71.
Westfield GH*, Rasmussen SG*, Su M*, Dutta S*, DeVree BT, Chung KY, Calinski D, Velez-Ruiz G, Oleskie AN, Pardon E, Chae PS, Liu T, Li S, Woods VL Jr, Steyaert J, Kobilka BK, Sunahara RK, Skiniotis G.Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc Natl Acad Sci. U S A. 2011, 108(38):16086-91. [* Equal contribution]
Gu L, Eisman EB, Dutta S, Franzmann TM, Walter S, Gerwick WH, Skiniotis G, Sherman DH. Tandem acyl carrier proteins in the curacin biosynthetic pathway promote consecutive multienzyme reactions with a synergistic effect. Angew Chem Int Ed Engl. 2011, 50(12):2795-98.
Dutta S, Mazumdar B, Banerjee KK, Ghosh AN. Three-dimensional structure of different functional forms of the Vibrio cholerae hemolysin oligomer: a cryo-electron microscopic study. J Bacteriol. 2010, 192(1):169-78.
“Kindness is the language which the deaf can hear and the blind can see”
Mark Twain
Quote
Course & Teaching
Electron microscopy and 3D image processing for Life sciences. (MB 212 JAN 2:0)
Electron microscopy and 3D image processing for Life sciences. (MB 222 JAN 3:0)
Advance course on Biological Cryo-EM sample preparation and 3D image reconstruction (2:1)
Transmission Electron Microscopy & Cryo-EM and single particle analysis
Previous Course-
Electron microscopy and 3D image processing for Life sciences. (MB 212 JAN 2:0). Academic year 2016-2022
Group Leader
Somnath Dutta
Associate Professor
Ph.D. from NICED, Kolkata, 2010
Post Doc. Skiniotis Lab, University of Michigan, Michigan, Ann Arbor, USA From 2010-2016
Assistant Profesor, MBU, IISc, Bangalore 2016-2022.
Associate Professor, MBU, IISc, Bangalore 2022-
Ph.D student
Surekha Padmanaban
I did my bachelor’s in biotechnology from Rajalakshmi Engineering College, Chennai, Tamil Nadu. Followed by master’s in medical biotechnology from Indian Institute of Technology, Hyderabad, Telangana. My interest in structural studies of macromolecular complexes has made me join Dr. Somnath’s lab in molecular biophysics department as a Ph.D student in August 2019.
surekhap@iisc.ac.in
Int. Ph.D. student
Bapan Mondal
Integrated Ph.D. student
Completed B.Sc. in Zoology (2019-22) from Ramakrishna Mission Vidyamandira, Howrah.
Int. PhD Student
Partho Pratim Das
Integrated PhD Student
Done Under graduation(2019-2022) from Ramakrishna Mission Vidyamandira, Belur
Ph.D. Student
Nayanika Sengupta
I am a PhD student since July 2018, in the lab of Dr Dutta. I pursued a BSc degree in Microbiology from St. Xavier’s College, Kolkata and went ahead to do an MSc in Biotechnology from the University of Calcutta. Currently, I am invested in deciphering high-resolution characteristics of Bacterial Secretion System proteins and Pore Forming Toxins.
nayanikas@iisc.ac.in
Ph.D. Student
Priyanka Garg
I did my B.E. and M.E. in Biotechnology from Panjab University Chandigarh. I joined MBU as a graduate student in July 2017.I am currently working on structural and functional characterisation of Non-ribosomal peptide synthetase of leinamycin biosynthetic pathway.
priyanka2@iisc.ac.in
Ph.D. student
Suman Mishra
I joined Dr. Somnath Dutta's lab in July 2019 as a Ph.D. student. Prior to this, I completed my Bachelor of Technology (B.Tech) degree in Biotechnology from D.Y. Patil University, School of Biotechnology and Bioinformatics, Navi Mumbai, and did my six-months dissertation at CSIR- Center for Cellular and Molecular Biology (CCMB, Hyderabad) under Dr. K. Thangaraj. In this lab, my interests primarily include structure elucidation of microbial proteins through cryo-EM.
sumanmishra@iisc.ac.in
Ph D Student MOLECULAR BIOPHYSICS UNIT
Dipanwita Mandal
I did my B.Tech in biotechnology from the National Institute of technology Durgapur. After that I joined MBU for my PhD degree. My research work is mainly focussed on Mycobacterium tuberculosis secretion system.
Postdoctoral Research fellow
Dr. Anupam Roy
I was a graduate student at the Structural Biology and Bioinformatics Division of CSIR-Indian Institute of Chemical Biology, Kolkata. I had received my Ph.D from University of Calcutta, where my research as a graduate student had focused primarily on the structural aspects of different amyloids aggregates.Currently I’m working as a Research Associate at the Advanced Center for Cryo-Electron Microscopy Facility in Dr. Somnath Dutta's Group, MBU-IISc and working in the field of Cryo-Electron Microscopy to understand structural overviews of bacterial pore-forming toxins and viral phage proteins using SPA Cryo-EM.
Ph.D. Student
Clayton Fernando R
I received my B. Tech and M.Tech degree in Biotechnology from Kalasalingam Academy of Research and Education and did my research projects in various premier research institutions such as CSIR-IICB, IISc, and Aravind Medical Research Foundation and published some research papers. Also, two times I'm selected as an INSA-NASI-IASc summer research fellow. Currently, I wish to explore macromolecular complexes involved in pathogenesis using the pioneering structural biology tool, Cryo-EM and will assist in the development of drugs and vaccines. In the same way, I'm maintaining the Cryo-EM facility.
Cryo-EM Manager
Prithiv kishore
He completed his Master of Science (M.Sc.) in Biomedical science (integrated M.Sc) in Bharathidasan university, Trichy (2017-2022). Currently he working as Cryo-Electron microscopy facility manager in ACCEM-IISc, helping research students and scientists from various institutes and industries to get high resolution images using state of the art Cryo-EM.
PhD Student
Sainath Polepalli
I completed my Bachelor of Technology (B.Tech) in Industrial Biotechnology from Alagappa College of Technology (ACTech), Anna University, Chennai (2016-2020). I am interested in learning the Protein Structure elucidation techniques. I joined Dr. Somanth Dutta’s lab in MBU as a Ph.D. student in 2020 to gain experience in Protein Structure determination using the Cryo-EM.
Ph.D. Student
Arnab Chatterjee A
Lab News
Arnab Chatterjee will present his recent work in ETOX 2023, EUROPEAN WORKSHOP ON BACTERIAL PROTEIN TOXINS organised by University of Dundee UK and University of Sheffield, UK.
Nayanika Sengupta will present her recent work in Mechanisms of Membrane Transport (GRS), Gordon Research Seminar in June 17 - 18, 2023 at Eurotel Victoria, Les Diablerets, VD, Switzerland.
https://www.msn.com/en-in/news/other/iisc-study-shows-forms-of-sars-cov2-s-protein/ar-AAKAq3N
https://www.iisc.ac.in/novel-insights-into-the-structure-of-sars-cov-2-spike-protein/
Recognizing the enormity of the challenges our society faces, DUTTA Lab (Cryo-EM Structural Biology lab) is dedicated to making a lasting impact through our programs. While our efforts are driven by our organization’s singular focus, we spread a wide net by investing in a variety of progressive strategies. Learn more about our initiatives and get involved yourself.
APMC Meeting Feb 2020
Past Fellows
1. ISHIKA PRAMANICK (July 2016-April 2022). Currently at Norwich BioScience Institutes, Colney, Norwich
2. Anil Kumar (July 2017-April 2021) Cryo-EM Manager. Currently at UW-Madison Cryo-EM Research Center.
3. Alakta Das (May 2017 - July 2021), UG student of IISc – BS & MS Thesis. Currently Darwin Trust Fellow PhD student, University of Edinburgh, Edinburgh, UK.
4. Anuradha Choudhary (Project Fellow) May 2016-May 2018. (Now a Ph.D. student at International Institute of Molecular and Cell Biology, Warsaw, Poland).
5. Haaris Ahsan Safdari (MS student 2017-2019).
6. Abirlal Mukherjee (Project Fellow) 2018-2019. (Now a Ph.D. student at the Indian Institute of Technology, Roorkee).
7. Manish Sarkar (Project Fellow) 2016-2017 (Now Ph.D. Student at Bose Institute, Kolkata).
8. Navyashree V (July-Sep 2017), Bangalore University – Summer training
9. Suresh Kumar (Project Fellow)
10. Akansha Patel (M.Tech Final Year Project Student) 2016-2017
11. Preeti (Postdoc May 2017-May 2018)
12. Ayushi Shukla (Project Fellow)
13. Puja – Summer training
14. Gyana Prakash Mahapatra (Project Assistant)
Contact DUTTA Lab (Cryo-EM Structural Biology lab)
Indian Institute of Science, Molecular Biophysics Unit, Annex building, 1st Floor, Bangalore 560012
080-2293 3453
