ABOUT

 

Bose Laboratory is focused on study of macromolecules involved in the apoptotic pathway and their implications in normal cellular functions and pathogenesis. The lab works on high temperature requirement family of serine proteases (HtrA); interaction between antiapoptotic c-FLIP and calmodulin; Bcl2 family proteins and their interacting partners. Moreover, the laboratory is entering into application-based translational research that includes enzymes involved in metabolic reprogramming and their role in altering cancer signaling pathway. Dr. Bose organized the Indo-US conference/workshop on 'Advances in Enzymology' in January 2017.

 

 

 

Dr Kakoli Bose

PI/Scientific Officer 'F'

  • Honors and Recognitions

    Recipient of National Women Bioscientist Award, Govt. of India, 2015 (Young Category) 

    Editorial Board Member, Biochem. J, Portland Press, UK.

  • Research Interests

    Biophysics, Biochemistry, Structural Biology, ChemicalBiology, Cell Biology, Enzymology and Computational Biology

    Research focused on macromolecules involved in alternate pathways of apoptosis and their associated diseases

     

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                                     RESEARCH

 

Highlights of the research findings at Bose Lab include elucidation of the structural basis of HtrA2 mutations that are implicated in diseased phenotypes. Crystallography data of one such mutants has been deposited in Protein Data Bank (PDB ID: 5WYN). The laboratory has made several important discoveries such as mode of interaction of HtrA2 with its natural substrate, identification of a novel binding partner as well as design of its promising inhibitors. These crucial pieces of information would provide means to manipulate HtrA2 with desired characteristics. The laboratory has developed a database comprising PDZ-domain containing proteins ‘PDZscape’, which is freely available to the users worldwide.

 

Ongoing Research Projects

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Identification and Characterization of Novel Binding Partner of Serine Protease HtrA2/Omi: A multidisciplinary Approach

The project involves understanding allosteric behavior of a proapoptotic serine protease HtrA2 so as to establish a unified model of its mechanism of action and develop ways of its modulation in different diseases it is associated with such as cancer.. 

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Investigating the molecular basis of CaM/c-FLIP interaction to design specific c-FLIP inhibitor for modulating its antiapoptotic function

With the information that Fas-mediated apoptosis and tumorigenesis are influenced by CaM/c-FLIP (oncoprotein) interaction, we aim at developing specific inhibitors that target the binding pocket of c-FLIP and thereby CaM/c-FLIP association. 

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Understanding the basis of Interaction between proapoptotic serine protease HtrA2/Omi and cell death regulatory protein GRIM-19

This project aims at elucidating GRIM-19-mediated allosteric activation of HtrA2 with an aim at designing peptide analogs that will promote HtrA2-mediated apoptosis. 

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Design and characterization of specific modulator for pro-apoptotic serine protease HtrA2/Omi

This project concerns design, synthesis and profiling of specific HtrA2/Omi inhibitor that might be useful for therapeutic intervention in diseases showcasing excessive caspase independent cell death.

 

PUBLICATIONS

Research Articles

 

  1. Doshi J, Kuppili R, Gurdasani S, Venkatakrishnan N, Saxena A, Bose K. (2018) PDZscape: a comprehensive PDZ-protein database. BMC Bioinformatics.Apr 25;19(1):160.

  2. Bhattacharya S, Reddy D, Jani V, Gadewal N, Shah S, Reddy R, Bose K, Sonavane U, Joshi R, Gupta S. (2017 ) Histone isoform H2A1H promotes attainment of distinct physiological states by altering chromatin dynamics. Epigenetics Chromatin. Oct 18;10(1):48

  3. Singh N, Senapati, S and Bose K. (2016) Insights into the mechanism of human papillomavirus E2-induced procaspase-8 activation and cell death. Sci. Rep., 016 Feb 24

  4. Bhattacharya S, Reddy D, Reddy R, Sharda A, Bose K, Gupta S.(2016). Incorporation of a tag helps to overcome expression variability in a recombinant host. iotechnol Rep (Amst). Jul 18;11:62-69

  5. Singh N, Hassan A, Bose K. (2015) Molecular basis of death effector domain chain assembly and its role in caspase-8 activation. FASEB J. Jan;30(1):186-200

  6. Singh N, Kanthaje S, Bose K. (2015) Equilibrium dissociation and unfolding of human papillomavirus E2 transactivation domain. Biochem Biophys Res Commun. 463(4):496-503

  7. Singh N, D’Souza A, Cholleti A, Sastry GM and Bose K. (2014) Dual regulatory switch confers tighter control on HtrA2 proteolytic activity. Febs J. 281, 2456-2470

  8. Chaganti LK, Kuppili RR, Bose K. (2013) Intricate structural coordination and domain plasticity regulate activity of serine protease HtrA2. FASEB J. 27(8):3054-3066. (Covered in IndianBioscience.org)

  9. Bejugam PR, Kuppili RR, Singh N, Gadewal N, Chaganti LK, Sastry GM, Bose K. (2013). Allosteric regulation of serine protease HtrA2 through novel non-canonical substrate binding pocket. PLoS One. 8(2):epub55416. Epub 2013 Feb 14

  10. Singh N, Kuppili RR, Bose K.(2011). The structural basis of mode of activation and functional diversity: a case study with HtrA family of serine proteases. Arch Biochem Biophys., Dec 15; 516(2):85-96

  11. Bose K, Meinke G, Bohm A and Baleja JD (2011). Design and characterization of an enhanced repressor of human papillomavirus E2 protein. FASEB J., Jul; 25(7), 2354-2361

  12. Wei J, Liu Y, Bose K, Henry GD and Baleja JD. (2009). Disorder and Structure in the Rab11 Binding Domain of Rab11 Family Interacting Protein 2. Biochemistry. Jan; 48(3), 549-557

  13. Bose K, Yoder NC, Kumar K and Baleja JD. (2007). The Role of Conserved Histidines in the Structure and Stability of Human Papillomavirus Type 16 E2 DNA Binding Domain. Biochemistry. 46:1402-1411

  14. Bose K and Clark AC. (2005). pH Effects on the Stability and Dimerization of Procaspase-3. Protein Sci.,  Jan; 14(1):24-36

  15. Bose K, Pop C, Feeney B, and Clark AC. (2003). An Uncleavable Procaspase-3 Mutant has a Lower Catalytic Efficiency but an Active Site Similar to That of Mature Caspase-3. Biochemistry. Oct 28; 42(42):12298-12310

  16. Bose K and Clark AC. (2001). Dimeric Procaspase-3 Unfolds via a Four-State Equilibrium Process. Biochemistry. Nov 27; 40(47):14236-14242. (Pioneer in the field)

  17. Pop C, Chen Y-R, Smith B, Bose K, Bobay B, Tripathy A, Franzen S and Clark AC. (2001). Removal of the Pro-domain Does Not Affect the Conformation of the Procaspase-3 Dimer. Biochemistry. 40(47):14224-14235

Book chapters

  1. Parui AL, Bose K (2017) Caspases: Regulatory Mechanisms and Their Implications in Pathogenesis and Therapeutics. Pathophysiological Aspects of Proteases. Nov 18; 423-488

  2. Wagh AR, Bose K (2017) Emerging Roles of Mitochondrial Serine Protease HtrA2 in Neurodegeneration. Proteases in Physiology and Pathology. Sep 12; 325-353

  3. Singh N, Bose K (2015) Apoptosis: pathways, molecules and beyond. Proteases in Apoptosis: Pathways, Protocols and Translational Advances. 1-30

  4. Acharya S, Kuppili RR, Chaganti LK, Bose K (2015) Proteases in Apoptosis: Protocols and Methods. Proteases in Apoptosis: Pathways, Protocols and Translational Advances. 143-202

  5. Kuppili RR, Bose K(2015) Calpains and Granzymes: Non-caspase Proteases in Cell Death. Proteases in Apoptosis: Pathways, Protocols and Translational Advances. 53-94

  6. Chaganti LK, Singh N, Bose K (2015) Cathepsins and HtrAs–Multitasking Proteases in Programmed Cell Death. Proteases in Apoptosis: Pathways, Protocols and Translational Advances. 95-141

LAB MEMBERS

 

Pandurang Padale

Technician 'F'

 

 

Snehal Pandav Mudrale

Scientific Assistant 'C'

 

 

Dr. Lalith Chaganti

Research Associate

 

 

Saujanya Acharya

PhD Research Scholar (SRF)

 

 

Ajay Wagh

PhD Research Scholar (SRF)

 

 

K Raghupati

PhD Research Scholar (SRF)

 

 

Aasna Parui

PhD Research Scholar (SRF)

 

 

Rashmi Puja

PhD Research Scholar (SRF)

 

 

Sucheta Chopra

PhD Research Scholar (JRF)

 

 

Rucha Kulkarni

PhD Research Scholar (JRF)

 

 

Shubhankar Dutta

Senior Research Fellow

 

 

Alumni

 

PhD Research Scholars

Dr. Nitu Singh

Dr. Raja Reddy Kuppili

 

 

 

Research and Post Doc Fellows

Dr. A K Senthil

Jitesh Doshi

Mriganka Mandal

 

 

 

 

Trainees

Navneet Venkatakrishnan

Amrutha Kale

 

 

SERVICES

 

Biophysics Facility

 

The ACTREC Biophysics facility houses an extensive array of sophisticated instruments for in vitro molecular-scale characterization of biological macromolecules with accuracy and precision. The facility provides services to different projects, enabling the characterization of the intrinsic properties of macromolecules and their assemblies (size, shape, folding and stability) and of the interactions in which they are involved (stoichiometry, thermodynamic and kinetic parameters). Biophysics facility is equipped with Jasco J-815 Circular Dichroism Spectropolarimeter, FluroLog -3 Modular Spectrofluorimeter, Dynamic Light Scattering (DLS) DynaPro Plate Reader II, BIAcore T200 for automated surface plasmon resonance (SPR), and MicroCal iTC200 isothermal titration calorimeter (ITC). Along with technically sound instrumentation, ACTREC biophysics facility also provides expertise to assist the users in experimental design and data interpretation, if required. Depending on individual requirements, either experiment can be performed for the users or help them to operate these instruments independently with minimal supervision. These services are also available for students, research scholars, and scientists from other academic institutions as well as industries on payment basis. During the year 2017, in addition to the in-house users, facility services were also used by the investigators and students from BARC, Bharathidasan University, Goa University, University of Mumbai, Bharath Serums Pvt Ltd, Premas Biotech Pvt Ltd etc.

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 Jasco J-815 Circular Dichroism Spectropolarimeter

 

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FluroLog Modular Spectrofluorimeter

CONTACT

Dr Kakoli Bose

 

Tata Memorial Centre - Advanced Centre for Treatment, Research and

Education in Cancer (TMC - ACTREC)

Sector 22, Kharghar, Navi Mumbai 410210

Contact

Phone: +91-22-2740-5109

E-mail: kbose@actrec.gov.in

 

 

 

 

 

Laboratory Contact

Phone: +91-22-2740-5330

bose.lab@actrec.gov.in