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Prof. Sharmistha Sinha

Professor, Scientist-F, Dean Academics, Former Head CBU

Bacterial microcompartments (BMCs) are unique paradigms of prokaryotic organelles that encapsulate certain metabolic reactions under specific microbial physiology. The Sinha lab is actively engaged in understanding the biogenesis pathogenesis in the bacterial microcompartments associalted with Salmonella enterica. The lab is partcularly interexted in the following concepts: BMCs as models to explore compartmentalization in biology and organelle biogenesis in Salmonella BMCs as targets to manage Salmonella BMCs as scaffolds for the development of smart nano-factories and nanomaterials The Sinha Lab is looking for highly motivated students eager to work in the interdisciplinary areas of disease biology and chemistry. Interested students may write to sinhas@inst.ac.in. Students with independent scholar recognition via CSIR/DBT/DST fellowships are welcome to apply.

Contact Information :

  • BMC in Salmonella Pathogenesis

  • Traditional methods of molecular confinement have physicochemical barriers that restrict the free passage of substrates/products. Here, we explored liquid–liquid phase separation as a method to restrain protein–metal nanocomposites within barrier-free condensates. Confinement within liquid droplets was independent of the protein's native conformation and amplified the catalytic efficiency of metal nanocatalysts by one order of magnitude.

  • A classic example of an all-protein natural nano-bioreactor, the bacterial microcompartment is a prokaryotic organelle that confines enzymes in a small volume enveloped by an outer protein shell. These protein compartments metabolize specific organic molecules, allowing bacteria to survive in restricted nutrient environments. In this work, 1,2-propanediol utilization microcompartment (PduMCP) was used as a model to study the effect of molecular confinement on the stability and catalytic activity of native enzymes in the microcompartment. A combination of enzyme assays, spectroscopic techniques, binding assays, and computational analysis were used to evaluate the impact of the major shell protein PduBB′ on the stability and activity of PduMCP′s signature enzyme, dioldehydratase PduCDE. While free PduCDE shows ∼45 % reduction in its optimum activity (activity at 37 °C) when exposed to a temperature of 45 °C, it retains similar activity up to 50 °C when encapsulated within PduMCP. PduBB′, a major component of the outer shell of PduMCP, preserves the catalytic efficiency of PduCDE under thermal stress and prevents temperature-induced unfolding and aggregation of PduCDE . We observed that while both PduB and PduB′ interact with the enzyme with micromolar affinity, only the PduBB′ combination influences its activity and stability, highlighting the importance of the unique PduBB′ combination in the functioning of PduMCP  ChemBioChem2022,23, e2021006.

Current Group Members

  • ISHANI SHARMA

    ISHANI SHARMA

    Email: ishani.ph23228@inst.ac.in

    Reg. No.: PH23228

  • MR. S M ROSE

    MR. S M ROSE

    Email: smrose.ph21234@inst.ac.in

    Reg. No.: PH21234

  • MS. AARCHA RADHAKRISHNAN

    MS. AARCHA RADHAKRISHNAN

    Email: aarcha.ph21202@inst.ac.in

    Reg. No.: PH21202

  • MS. PREETI NEGI

    MS. PREETI NEGI

    Email: preeti.ph20209@inst.ac.in

    Reg. No.: PH20209

  • MS. DIMPLE GOEL

    MS. DIMPLE GOEL

    Email: dimple.ph20210@inst.ac.in

    Reg. No.: PH20210

  • MS.SIMERPREET KAUR

    MS.SIMERPREET KAUR

    Email: simerpreet.ph17224@inst.ac.in

    Reg. No.: PH17224

  • MS. HARPREET KAUR

    MS. HARPREET KAUR

    Email: harpreet.ph19201@inst.ac.in

    Reg. No.: PH19201

  • MS. SILKY

    MS. SILKY

    Email: silky.ph19202@inst.ac.in

    Reg. No.: PH19202

Alumni

  • MR. GAURAV KUMAR

    MR. GAURAV KUMAR

    Reg. No.: Ph17202

    Designation: PhD Scholar

    Aug 2017 - Feb 2023

  • MS. ANKUSH GARG

    MS. ANKUSH GARG

    Reg. No.: PH15206

    Designation: PhD Scholar

    Aug 2015 - Dec 2021

  • MR. NAIMAT KALIM BARI

    MR. NAIMAT KALIM BARI

    Reg. No.: PH14210

    Designation: PhD Scholar

    Aug 2014 - Jul 2020

  • 1.

    Self-assembly of Shell Protein and Native Enzyme in a Crowded Environment Leads to Catalytically Active Phase Condensates: , Gaurav Kumar, Sharmistha Sinha , (2023) , just accepted: just accepted , Biochemical Journal , 10.1042/BCJ20220551

  • 2.

    Disordered regions endow structural flexibility to shell proteins and function towards shell-enzyme interactions in propane diol utilization microcompartment: , Gaurav kumar, Jagadish Prasad Hazra, Sharmistha Sinha , (2022) , just accepted: , Journal of Biomolecular Structure & Dynamics

  • 3.

    Barrier-free liquid condensates of nanocatalysts as effective concentrators of catalysis: , Silky Bedi, Gaurav Kumar, S. M. Rose, Sabyasachi Rakshit, and Sharmistha Sinha , (2022) , 58: 8634-8637 , Chemical Communications , DOI https://doi.org/10.1039/D2CC03111F

  • 4.

    A Major Shell Protein of 1, 2‐Propanediol Utilization Microcompartment Conserves the Activity of Its Signature Enzyme at Higher Temperatures: , Gaurav Kumar, Naimat K. Bari,Jagadish P. Hazra,Dr. Sharmistha Sinha , (2022) , 23,: e2021006. , ChemBioChem , https://doi.org/10.1002/cbic.202100694

  • 5.

    Varying protein architectures in 3-dimensions for scaffolding and modulating properties of catalytic gold nanoparticles: , Simerpreet Kaur,Naimat K Bari,Sharmistha Sinha , (2022) , Just accepted: Just accepted , Amino Acids , 10.1007/s00726-022-03127-7

  • 6.

    Doxorubicin induced aggregation of α-synuclein: Insights into the mechanism of drug induced Parkinsonism: , Ankush Garg,Sharmistha Sinha , (2022) , 212: 112371. , Colloids and Surfaces B: Biointerfaces , 10.1016/j.colsurfb.2022.112371

  • 7.

    Factors deciding the assembly and thermostability of the DmrB cage: , Ankush Garg,Sharmistha Sinha , (2021) , 959-967, 182: 959-967 , International Journal of Biological Macromolecules 182

  • 8.

    Naturally occurring protein nano compartments: basic structure, function, and genetic engineering: , Dimple Goel,Sharmistha Sinha , (2021) , 2 (4): 042001 , Nano Express , 10.1088/2632-959X/ac2c93/

  • 9.

    Biophysical approaches to understand and re-purpose bacterial microcompartments: , Gaurav Kumar,Sharmistha Sinha , (2021) , 63,: 43-51. , Current Opinion in Microbiology , 10.1016/j.mib.2021.05.008

  • 10.

    Protein morphology drives the structure and catalytic activity of bio-inorganic hybrids: , Harpreet Kaur,Naimat K Bari,Ankush Garg,Sharmistha Sinha , (2021) , Just Accepted: , International Journal of Biological Macromolecules , 10.1016/j.ijbiomac.2021.01.217

  • 11.

    Probe into a Multi-Protein Prokaryotic Organelle Using Thermal Scanning Assay Reveals Distinct Properties of the Core and the Shell: , Dr. Naimat K Bari ,Jagadish P Hazra ,Gaurav Kumar,Simerpreet Kaur,SHARMISTHA SINHA , (2020) , 1864(10): 129680 , BBA - General Subjects , 10.1016/j.bbagen.2020.129680

  • 12.

    Temporal control in tritylation reactions through light-driven variation in chloride ion binding catalysis–A proof of concept: , Surbhi Grewal Saonli Roy Himanshu Kumar Mayank Saraswat Naimat K Bari Sharmistha Sinha Sugumar Venkataramani , (2020) , 10 (20): 7027-7033. , Catalysis Science & Technology , 10.1039/D0CY01090A

  • 13.

    Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties: , Ankush Garg , Jagadish Prasad Hazra 2, Malay Kumar Sannigrahi 2, Sabyasachi Rakshit 3, Sharmistha Sinha , (2019) , 118 (3): 720-728 , Biophysical Journal , 10.1016/j.bpj.2019.12.015

  • 14.

    Functional protein shells fabricated from the self-assembling protein sheets of prokaryotic organelles: , Naimat K. Bari, Gaurav Kumar , Jagadish P. Hazra, Simerpreet Kaur ,Sharmistha Sinha , (2019) , 8: 523-533 , Journal of Materials Chemistry B , https://doi.org/10.1039/C9TB02224D

  • 15.

    Cellulose-metallothionein matrix for metal binding: , Naimat K.Bari ,Shaswat Barua ,Ankush Garg,Malay K Sannigrahi,Sharmistha Sinha , (2018) , 192: 126-134 , Carbohydrate polymers , 10.1016/j.carbpol.2018.03.043

  • 16.

    Nanoparticle Fabrication on Bacterial Microcompartment Surface for the Development of Hybrid Enzyme-Inorganic Catalyst.: , Naimat Kalim Bari , Gaurav Kumar, Aashish Bhatt, Jagadish Prasad Hazra, Ankush Garg, Md. Ehesan Ali , (2018) , 8: 7742–7748 , ACS Catal. , 10.1021/acscatal.8b02322

  • 17.

    The Wrappers of the 1,2-Propanediol Utilization Bacterial Microcompartments.: , Naimat K Bari, Gaurav Kumar, Sharmistha Sinha , (2018) , 1112: 333-344. , Adv Exp Med Biol , 10.1007/978-981-13-3065-0_23

  • 18.

    Enhanced bacterial cellulose production from Gluconobacter xylinus using super optimal broth: , Prathna T. Chandrasekaran, Naimat Kalim Bari , (2017) , 24(10): 4367–4381 , Cellulose

  • 19.

    Selective molecular transport through the protein shell of a bacterial microcompartment organelle: , Chowdhury C, Chun S, Pang A, Sawaya MR, Sinha S, Yeates TO, Bobik TA , (2015) , 112(10): 2990-5. , Proc Natl Acad Sci U S A. , 10.1073/pnas.1423672112

  • 20.

    Alanine scanning mutagenesis identifies an asparagine-arginine-lysine triad essential to assembly of the shell of the Pdu microcompartment: , Shouqiang Cheng, Yea Won Sung, Dan E. McNamara, Michael R. Sawaya, Todd O. Yeates, Thomas A. Bobik. J. , (2014) , 26(12): 2328-45. , J. Mol. Biol. , 10.1016/j.jmb.2014.04.012

  • 21.

    Diverse bacterial microcompartment organelles: , Chowdhury C, Sinha S, Chun S, Yeates TO, Bobik TA , (2014) , 78(3): 438-68 , Microbiol Mol Biol Rev , 10.1128/MMBR.00009-14

  • 22.

    A Key Role for Lysine Residues in Amyloid β-Protein Folding, Assembly, and Toxicity: , Sharmistha Sinha,Dahabada H. J. Lopes,Gal Bitan. ACS Chem. Neurosci. , (2012) , 3 (6): 473–481. , ACS Chem. Neurosci. , 10.1021/cn3000247

  • 23.

    Interactions between the termini of lumen enzymes and shell proteins mediate enzyme encapsulation into bacterial microcompartments: , Sharmistha Sinha , (2012) , 109(37): 14995-5000. , PNAS , 10.1073/pnas.1207516109

  • 24.

    Comparison of Three Amyloid Assembly Inhibitors: The Sugar Scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01: , Sharmistha Sinha 1, Zhenming Du, Panchanan Maiti, Frank-Gerrit Klärner, Thomas Schrader, Chunyu Wang, Gal Bitan , (2012) , 3(6): 451-8. , ACS Chemical Neuroscience , DOI: 10.1021/cn200133x

  • 25.

    Lysine-Specific Molecular Tweezers Are Broad-Spectrum Inhibitors of Assembly and Toxicity of Amyloid Proteins: , Sharmistha Sinha, Dahabada H. J. Lopes, Zhenming Du, Eric S. Pang, Akila Shanmugam, Aleksey Lomakin, Peter Talbiersky, Annette Tennstaedt, Kirsten McDaniel, Reena Bakshi, Pei-Yi Kuo, Michael Ehrmann, George B. Benedek, Joseph A. Loo, Frank-Gerrit Klärner, Thomas Schrader, Chunyu Wang, and Gal Bitan J. Am. Chem. Soc , (2011) , 133 (42): 16958–16969. , J. Am. Chem. Soc. , 10.1021/ja206279b

  • 1.

    Application of Photochemical Cross-linking to the Study of Oligomerization of Amyloidogenic Proteins: , Lopes DHJ, C Rosensweig, G Bitan , (2012) , 849: 11-21 , Methods Mol Biol.

  • 2.

    Amyloids and Protein Aggregation—Analytical Methods: , Li H, F Rahimi, K Murakami, P Maiti, G Bitan , (2009) , Encyclopedia of Analytical Chemistry
  • 1. Xviii International Symposium On Glycoconjugates (glyco-18): , Florence, Italy, (2005)
  • 2. Molecular Tweezers For The Treatment Of Amyloid-related Diseases: , P. Talbiersky, A. Lomakin, F.-G. Klärner, T. Schrader, S. Frautschy,G. Bitan , (2010)
  • 3. New Compounds For The Treatment Of Diseases Related To Protein Misfolding: , T Schrader, K Hochdorffer, J Marz-Berberich, L Nagel-Steger, G Bitan , (2010)

  • 1.

    The 56th Biophysical Society Meeting: , SanDiego, CA , (2012)

  • 2.

    The 23rd Symposium of the Protein Society, Boston: , MA , (2009)

  • 3.

    XVII International Symposium on Glycoconjugates (GLYCO-17): , Bangalore , (2002)

  • Research Associate:Indian Institute of Science, Bangalore,, India (April 2007 to April 2008 )

  • Postdoctoral Fellow:Dept. of Neurology, University of California, Los Angeles,, USA (March 2008 to March 2010 )

  • Postdoctoral Fellow:Dept. of Biochem. Biophys. and Mol. Biol., Iowa State University, Ames,, USA (April 2010 to April 2013 )

  • Title: Cell-free bioreactors from the shell proteins of bacterial microcompartments

    PI: Prof. Sharmistha Sinha

    Funding Amount: 47 lakhs

    Tenure: 3 years

    Funding Agency: SERB

  • Title: Cellulose-protein binary conjugates for metal detoxification

    PI: Prof. Sharmistha Sinha

    Funding Amount: 18 lakhs

    Tenure: 3 years

    Funding Agency: SERB-Women Excellence Award

  • Title: Exploring the shell proteins of BMCPs as potential substrate for fabrication of Organic-Inorganic Hybrid Nanomaterials

    PI: Prof. Sharmistha Sinha

    CO-PI: Prof. Ehesan Ali

    Funding Amount: 47 lakhs

    Tenure: 3 years

    Funding Agency: DST Nano Mission

  • Title: Understanding the Forces Involved in the Packing of Enzymes Inside the Bacterial Microcompartments for the Development of Novel Encapsulated Bio-Systems

    PI: Prof. Sharmistha Sinha

    Funding Amount: 58 lakhs

    Tenure: 3 years

    Funding Agency: DBT

  • Title: Biological treatment of engineered nanomaterials-contaminated wastewater-feasibility and implication

    PI: Dr. Sonalika Vaidya Role

    CO-PI: Prof. Sharmistha Sinha

    Funding Amount: 10 Lakhs (completed)

    Tenure: 2 years

    Funding Agency: INST