Molecular Immunology & Cellular Microbiology Laboratory
In context of the Indian sub-continent, Tuberculosis and Visceral Leishmaniasis are dreadful infectious diseases caused by Mycobacterium tuberculosis and Leishmania donovani respectively. The advent of extreme drug resistance has aggravated the situation. The search for newer molecular targets as well as alternative therapeutic strategies is clearly evident.
Using CRISPR/Cas9 mediated genome editing our lab tries to have a thorough understanding of the host factors governing parasite pathogenesis. We are looking into the roles of phosphatases and kinases in mediating parasite survival. Biochemical assays are being set-up for the functional characterization of macrophage factors phosphorylated by mycobacteria secreted virulence factors. Functional characterization and adaptive resistance mechanism studies are carried out for an essential Leishmania enzyme. Besides, the role of host factors that enable controlled phagosome maturation and hinder macrophage apoptosis in context of mycobacteria and those allowing efficient promastigote to amastigote differentiation as well as factors dampening macrophage proliferation but promoting amastigote proliferation in context of Leishmania are being studied.
We are also trying to envisage into host-directed immunomodulatory therapeutics against mycobacterial infection that would help overcome the pathogen-induced classical macrophage activation block and thereby re-enable them to kill the parasite. Drug repurposing approaches against Leishmania specific enzymes using tri-cyclic anti-depressants are also being carried out whose application through the creation of reticulo-endothelial blockade would be tried out.
We are also engaged in developing non-invasive, rapid, low-cost, point-of-care screening platform for latent TB and rapid, point of care diagnostics for drug resistant TB.
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Activation of the cAMP/protein kinase A signalling pathway by coronin 1 is regulated by cyclin-dependent kinase 5 activity. Liu X*, BoseDasgupta S*, Jayachandran R, Studer V, Rühl S, Stiess M, Pieters J.(*contributed equally) By FEBS Journal 590(2) 279-87 (2016)
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A novel ATP binding cassette transporter, ABCG6 is involved in chemoresistance of Leishmania 9. BoseDasgupta S., Ganguly A., Roy A., Mukherjee T and Majumder HK. By Molecular Biochemical Parasitology 158(2) 176-88 (2008)
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Cytokine-Induced Macropinocytosis in Macrophages is regulated by 14-3-3ζ through its Interaction with Serine-Phosphorylated Coronin. (Journal Cover and Editors Choice Article with Podcast) BoseDasgupta S and Pieters J By FEBS Journal 282(7) 1167-81 (2015)
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Coronin 1 regulates cognition and behavior through modulation of cAMP/protein kinase A signaling. Jayachandran R*, Liu X*, BoseDasgupta S*, Mueller P*, Zhang LC, Genoud JS, Fossoud C, Gambino F., Khelfaoui M, Steiss M, Luthi A., Humeau Y and Pieters J (*contributed equally)) By PLoS Biology 12(3) - (2014)
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Coronin 1 trimerization is essential to protect mycobacteria within macrophages from lysosomal delivery BoseDasgupta S and Pieters J. By FEBS Letters 588(21) 3898-905 (2014)
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Inflammatory stimuli reprogram Macrophage phagocytosis to macropinocytosis for the rapid elimination of pathogens. (Journal Cover Article)) BoseDasgupta S and Pieters J By PLoS Pathogens 10(4) - (2014)
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Striking the Right Balance Determines TB or Not TB. BoseDasgupta S, Pieters J. By Frontiers in Immunology 5 - (2014)
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The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFLAP1 and LdTatD BoseDasgupta S, Das BB, Sengupta S, Roy A, Ganguly A, Tripathi G and Majumder HK By Cell Death & Differentiation 15(10) 1629-40 (2008)
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The large subunit of Leishmania topoisomerase I functions as the molecular steer in type IB topoisomerase. BoseDasgupta S., Ganguly A., Das BB., Roy A., Khalkho NVM. and Majumder HK By Molecular Microbiology 67 31-46 (2008)
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Amino acids 39-456 of large subunit and 210-262 of small subunit constitute the minimal, functionally interacting fragments of the unusual heterodimeric topoisomerase IB of Leishmania BoseDasgupta S, Das BB, Sengupta S, Ganguly A, Roy A., Tripathi G and Majumder HK By Biochemical Journal 409 481-9 (2008)
Principal Investigator
- Delineating the mechanism of anti-leishmanial activity of Tricyclic antidepressant Norclomipramine for drug repurposing studies
- Elucidating the Mechanism of S-nitrosylation of Mycobacteria Secreted Protein Kinase G (PknG) and its Consequent Phosphorylation of Macrophage Suppressor of Death Domain (SODD) in Hindering Macrophage Apoptosis
- Elucidating the role of mycobacteria secreted Protein Kinase G (PknG) mediated phosphorylation of macrophage Proteasome Modulator 9 (PSMD9) and its implication in hindering macrophage apoptosis.
- Establishing a State-of the-Art Hybrid BSLIII Facility at IIT Kharagpur to Facilitate Fundamental Research and Development of Diagnostics and Therapeutics Against Class III Pathogen Caused Viral and Bacterial Diseases
- Host-directed Therapy against Tuberculosis using Vitamin D Constituted Surface Functionalized Nanocapsiles Loaded with Immunomodulatory Drug
Ph. D. Students
Arjun Sankhla
Area of Research: Host-Pathogen Interaction
Arnab Hazra
Area of Research: Mycobacterial pathogenesis
Debayan Das
Area of Research: Infectious Disease Biology
Payel Das
Area of Research: Infection Biology
Rishika Jana
Area of Research: Biochemistry of Leishmania parasite
Sadhana Roy
Area of Research: Molecular Immunology and Cellular Microbiology
Saradindu Saha
Area of Research: Host-parasite interaction and therapeutics
Sayantani Datta
Area of Research: Molecular Immunology and Cellular Microbiology