WELCOME TO DUTTA LAB
Cryo-EM Structural Biology lab
My group is focusing on the structural studies of polyketide synthase, non-ribosomal peptide synthase, pore forming toxin, bacterial secretion system, 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).
1. Metabolic pathways of Mycobacterium tuberculosis
2. Pore-forming toxins
3. Bacterial secretion systems
4. Polyketide Synthases and nonribosomal peptide synthetases
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.
Research Publications in International Journals 2016-2020 (Assistant Professor)
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.
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.
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”
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 212 JAN 2:0)
Objectives and basic principles of different types of microscopes. Different types of electron microscopies and their applications. Basic introduction of electron microscopy physics and optics. Principles of image formation, Fourier analysis, Contrast Transfer Function and point spread function. Advanced sample preparation, imaging, data collection techniques of bio-molecules by negative staining and cryo-electron microscopy. Theoretical, computational and practical aspects of various advanced 3D image processing techniques. Cryo-EM map interpretation and data analysis, validation, molecular docking (use of Chimera, VMD) and application of Molecular Dynamics Flexible Fitting (MDFF).
CRYO-EM AND SINGLE PARTICLE ANALYSIS
Practical application and hands-on training of cryo-EM sample preparation, imaging and image processing.
TRANSMISSION ELECTRON MICROSCOPY
Practical application and hands-on training of TEM sample preparation, and imaging.
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
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.
I finished my M.Sc from the University of Calcutta in Microbiology. I joined DUTTA Lab (Cryo-EM Structural Biology lab) in 2016 with the vision and drive to learn single-particle cryo-EM and protein biochemistry. I am working on several projects of metabolic enzymes and SARS-CoV-2 spike protein. My future interest is the structural characterization of biomolecules by cryo-electron tomography.
M.Sc (Research) student
I am a final year undergraduate student at the Indian Institute of Science. I am working on Mycobacterial secretion system as a part of my final year project at the Dutta Lab. I am learning Cryo-EM, the cutting edge structural Biology tool and wish to pursue my future research career in the related field. Besides Science, I also take interest in writing poetry, playing ukulele and dancing Kathak.
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.
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.
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.
Post doctoral Fellow & DBT/Wellcome Trust India Alliance Early Career Fellow
DR. RUPAM BISWAS
I received my Bachelor's degree in Physics in 2008 and my Master's degree in Biophysics from Kalyani University in 2010. Soon after, I joined the Indian Institute of Technology (IIT) Kharagpur for a Ph.D. in Structural Biology program and received my Ph.D. in 2018. My doctoral research work at Dr. Amit Kumar Das’s laboratory entailed structural and biochemical insights into the enzymes involved in the type II pathway of bacterial fatty acid synthase. For my Postdoctoral research, I joined Dr. Dutta’s laboratory in 2018 to study the structural mechanisms of multidrug transporter complexes using cryo-electron microscopy
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.
ANIL KUMAR S
I completed my M.Sc in Biotechnology from Loyola college Chennai . Prior to this I completed my Bachelors in Biotechnology from Christ university. I am Maintaining cryo-EM facility at IISc, Bangalore.
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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.
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
EDUCATION & OUTREACH
PROF. RICHARD HENDERSON AND MY GROUP
1. Alakta Das (May - June 2017), UG student of IISc – Summer training
2. Navyashree V (July-Sep 2017), Bangalore University – Summer training
3. Anuradha Choudhary (Project Fellow) May 2016-May 2018. (Now Ph.D. student at International Institute of Molecular and Cell Biology,Warsaw, Poland)
4. Abirlal Mukherjee (Project Fellow) 2018-2019. (Now Ph.D. student at Indian Institute of Technology, Roorkee)
5. Manish Sarkar (Project Fellow) 2016-2017 (Now Ph.D. Student at Bose Institute, Kolkata)
6. Suresh Kumar (Project Fellow)
7. Akansha Patel (M.Tech Final Year Project Student) 2016-2017
8. Preeti (Postdoc May 2017-May 2018)
9. Ayushi Shukla (Project Fellow)
10. Puja – Summer training
11. Haaris Ahsan Safdari (MS student 2017-2019)
12. Gyana Prakash Mahapatra (Project Assistant)
CONTACT DUTTA LAB (CRYO-EM STRUCTURAL BIOLOGY LAB)
Indian Institute of Science, Molecular Biophysics Unit, Annex building, Bangalore