Faculty Directory

Dr. Sharmistha Sinha

Associate Professor, Scientist-E, Dean Academics, Former Head CBU

Bacterial microcompartments (BMCs) are unique paradigms of prokaryotic organelles that encapsulate certain metabolic reactions under specific microbial physiology. The structural components of a BMC include a selectively permeable shell along with sequestered enzymes. The sequence and structure of the shell proteins are conserved across all genres of the BMCs, while the encapsulated enzymes determine the type and function of the BMCs.  The shell protein genes cluster along with the enzymes in an operon of the genome of the organism and are induced upon a specific physiological stimuli. The main purpose of the BMCs is to isolate a metabolic process and sequester any toxic intermediate involved in the pathway and to properly orchestrate them into specific downstream pathway.  Recent reports indicate that BMC genes are identified in more that 20 bacterial phyla including several bacterial species in the human microbiome. More importantly, BMCs are also associated with cancer in the gut. The existing knowledge on BMCs so far calls for further exploration. Biochemical or structural studies on the BMCs will aid their use in biotechnology or as biomarkers for certain human physiological conditions.

In our lab we use BMCs as models to explore the following:


BMCs as models to explore compartmentalization in biology and organelle biogenesis

Using a combination of biochemical, molecular biology, biolphysical tools, we have demonstrated the biogenesis of the 1,2-propanediol utilization microcompartments in Salmonella. We have also shown the protein components required for the initial nucleation of the catalytic organelle. Our studies for the first time indicate chaperone like activity of certain components of the shell. We also demonstrate that the physical compartmentalization by the shell is preceded by liquid-liquid phase separation of the shell-enzyme combination. The liquid-liquid phase separated shell enzyme co-localized combination  shows enhanced catalytic activity. Further, minimalistic compartments developed using single shell proteins demonstrated similar activity with encapsulated native enzyme but altered activities with not native encapsulants (Bari et, al, BBA, 2020a; Bari et, al, JMCB 2020b; Kumar et, al, Chem.Bio.Chem,2022;)

 BMCs as scaffolds for the development of smart nanobiomaterials

We have developed BMC based hybrid catalyst systems with tunable catalytic activity. The shell proteins of the BMCs are used as scaffolds to prepare the hybrid catalysts. One of our hybrid catalysts, where we have fabricated gold nanoparticles on the outer shell of the BMC, can simultaneous act as an enzyme catalyst and also perform inorganic reduction reaction by gold nanoparticles. (Bari et. al., 2018; Kaur et. al., 2021)

 

 

 

 

CONTACT INFORMATION :

Research Interest

  • Protein Self Assembly and Disease Progression.
  • Molecular Confinement and SAR in Prokaryotic Organelles.
  • Novel Functional Organic-Inorganic Hybrid Materials.

Research Highlights

  • Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties

    This work stems from an interesting observation that genetic mutations result in the switching of one amino acid to different variants at the same codon show different cancer pathogenesis. We are trying to comprehend the molecular mechanism for the variation in gain-of-function opted by these variants. Several complementary experiments aided with computational studies show that residue-specific mechanism of unfolding and self-assembly of the entire protein might be one of the crucial parameters for their different oncogenic traits. These studies thus call for the need for developing therapeutic strategies that consider the resultant mutant-variant as a target rather than a mutation position. This is an important lead towards the understanding of the molecular contribution of p53 mutant aggregation in cancer.

    (Biophys. J. Volume 118, Issue 3, 2020, Pages 720-728, https://doi.org/10.1016/j.bpj.2019.12.015 )


PhD Students

  • MR. S M ROSE

    Email: smrose.ph21234@inst.ac.in

    Reg. No.: PH21234

    Working Since Jan, 2022
  • MS. AARCHA RADHAKRISHNAN

    Email: aarcha.ph21202@inst.ac.in

    Reg. No.: PH21202

    Working Since Aug, 2021
  • MS. PREETI NEGI

    Email: preeti.ph20209@inst.ac.in

    Reg. No.: PH20209

    Working Since Aug, 2020
  • Ms. DIMPLE GOEL

    Email: dimple.ph20210@inst.ac.in

    Reg. No.: PH20210

    Working Since Aug, 2020
  • Ms.Simerpreet Kaur

    Email: simerpreet.ph17224@inst.ac.in

    Reg. No.: PH17224

    Working Since Jan, 2018
  • Ms. Harpreet Kaur

    Email: harpreet.ph19201@inst.ac.in

    Reg. No.: PH19201

    Working Since Aug, 2019
  • Mr. Gaurav Kumar

    Email: gaurav.phd17202@inst.ac.in

    Reg. No.: Ph17202

    Working Since Aug, 2017
  • Ms. Silky

    Email: silky.ph19202@inst.ac.in

    Reg. No.: PH19202

    Working Since Aug, 2019

PhD Students

  • Ms. Ankush Garg

    Email: ankush@inst.ac.in

    Reg. No.: PH15206

  • Mr. Naimat Kalim Bari

    Email: barinaimat@gmail.com

    Reg. No.: PH14210


  1. 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) Journal of Biomolecular Structure & Dynamics, just accepted: .

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

  3. 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) ChemBioChem, 23,: e2021006. DOI: https://doi.org/10.1002/cbic.202100694

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

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

  6. Factors deciding the assembly and thermostability of the DmrB cage: Ankush Garg,Sharmistha Sinha, (2021) International Journal of Biological Macromolecules 182, 959-967, 182: 959-967. DOI: 10.1016/j.ijbiomac.2021.04.040

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

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

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

  10. 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) Catalysis Science & Technology, 10 (20): 7027-7033. DOI: 10.1039/D0CY01090A

  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) BBA - General Subjects, 1864(10): 129680. DOI: 10.1016/j.bbagen.2020.129680

  12. 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) Biophysical Journal, 118 (3): 720-728. DOI: 10.1016/j.bpj.2019.12.015

  13. 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) Journal of Materials Chemistry B, 8: 523-533. DOI: https://doi.org/10.1039/C9TB02224D

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

  15. 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) ACS Catal., 8: 7742–7748. DOI: 10.1021/acscatal.8b02322

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

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

  18. 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) Proc Natl Acad Sci U S A., 112(10): 2990-5. DOI: 10.1073/pnas.1423672112

  19. 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) J. Mol. Biol., 26(12): 2328-45. DOI: 10.1016/j.jmb.2014.04.012

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

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

  22. 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) ACS Chemical Neuroscience, 3(6): 451-8. DOI: DOI: 10.1021/cn200133x

  23. 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) ACS Chem. Neurosci., 3 (6): 473–481. DOI: 10.1021/cn3000247

  24. 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) J. Am. Chem. Soc., 133 (42): 16958–16969. DOI: 10.1021/ja206279b

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

  2. Amyloids and Protein Aggregation—Analytical Methods: Li H, F Rahimi, K Murakami, P Maiti, G Bitan., (2009) Encyclopedia of Analytical Chemistry., .

  1. New compounds for the treatment of diseases related to protein misfolding: T Schrader, K Hochdorffer, J Marz-Berberich, L Nagel-Steger, G Bitan, (2010) .

  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. XVIII International Symposium on Glycoconjugates (GLYCO-18): Florence, Italy, (2005) .

  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) .

Fundings

  • Understanding the Forces Involved in the Packing of Enzymes Inside the Bacterial Microcompartments for the Development of Novel Encapsulated Bio-Systems 3y, DBT, GoI
    Funding Amount: 58 lakhs
    PI: Dr. Sharmistha Sinha
  • Exploring the shell proteins of BMCPs as potential substrate for fabrication of Organic-Inorganic Hybrid Nanomaterials 3y, DST Nano Mission
    Funding Amount: 47 lakhs
    PI: Dr. Sharmistha Sinha Co-PI: Prof. Ehesan Ali
  • Cellulose-protein binary conjugates for metal detoxification 3y, SERB-Women Excellence Award
    Funding Amount: 18 lakhs
    PI: Dr. Sharmistha Sinha
  • Cell-free bioreactors from the shell proteins of bacterial microcompartments 3y, SERB
    Funding Amount: 47 lakhs
    PI: Dr. Sharmistha Sinha
  • Biological treatment of engineered nanomaterials-contaminated wastewater-feasibility and implication Two Years, INST
    Funding Amount: 10 Lakhs (completed)
    Role PI: Dr. Sonalika Vaidya Role Co-PI: Dr. Sharmistha Sinha

  • 2006

    PhD (Biophysics)

    Molecular Biophysics Unit, Indian Institute of Science, Bangalore, INDIA.

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

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

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

Awards & Honours


Professional Recognitions