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-parasite interactions, the role of certain host factors as well as parasite virulence factors. We are trying to develop a host-directed immunomodulatory therapy using drug loaded, surface functionalized mesoporous particles in an aerosolic formulation that would overcome the mycobacteria-induced macrophage activation block and thereby kill the parasite. In parallel we are also engaged in developing a low-cost, point-of-care diagnostic kit for extreme drug resistant TB, which would give results in hours rather than a month.
In context of Leishmaniasis we have characterized DNA Topoisomerase IA from Leishmania (LdTOPIA), which is a prokaryotic TopA homolog, is absent in higher eukaryotes and is an essential enzyme to resolve polycistronic transcription generated R-loops in the near-intron less Leishmania genome. Through inhibitor screening we have identified tricyclic anti-depressants (TCA?s) as potent inhibitors of LdTOPIA. Through drug repurposing we are generating TCA derivatives with increased efficiency which we plan to encapsulate in surface functionalized physiological agents and deliver through reticuloendothelial blockade. Apart from this we are studying the role of host factors that enable controlled phagosome maturation allowing efficient promastigote to amastigote differentiation as well as factors that dampen macrophage proliferation but promotes amastigote proliferation.
Activation of the cAMP/protein kinase A signalling pathway by coronin 1 is regulated by cyclin-dependent kinase 5 activity. by Liu X*, BoseDasgupta S*, Jayachandran R, Studer V, Rühl S, Stiess M, Pieters J.(*contributed equally) FEBS Journal 590(2) 279-87 (2016)
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) by BoseDasgupta S and Pieters J FEBS Journal 282(7) 1167-81 (2015)
Coronin 1 regulates cognition and behavior through modulation of cAMP/protein kinase A signaling. by 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)) PLoS Biology 12(3) - (2014)
Coronin 1 trimerization is essential to protect mycobacteria within macrophages from lysosomal delivery by BoseDasgupta S and Pieters J. FEBS Letters 588(21) 3898-905 (2014)
Inflammatory stimuli reprogram Macrophage phagocytosis to macropinocytosis for the rapid elimination of pathogens. (Journal Cover Article)) by BoseDasgupta S and Pieters J PLoS Pathogens 10(4) - (2014)
Striking the Right Balance Determines TB or Not TB. by BoseDasgupta S, Pieters J. Frontiers in Immunology 5 - (2014)
The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFLAP1 and LdTatD by BoseDasgupta S, Das BB, Sengupta S, Roy A, Ganguly A, Tripathi G and Majumder HK Cell Death & Differentiation 15(10) 1629-40 (2008)
The large subunit of Leishmania topoisomerase I functions as the molecular steer in type IB topoisomerase. by BoseDasgupta S., Ganguly A., Das BB., Roy A., Khalkho NVM. and Majumder HK Molecular Microbiology 67 31-46 (2008)
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 by BoseDasgupta S, Das BB, Sengupta S, Ganguly A, Roy A., Tripathi G and Majumder HK Biochemical Journal 409 481-9 (2008)
A novel ATP binding cassette transporter, ABCG6 is involved in chemoresistance of Leishmania by 9. BoseDasgupta S., Ganguly A., Roy A., Mukherjee T and Majumder HK. Molecular Biochemical Parasitology 158(2) 176-88 (2008)
Delineating the Molecular Intercome of Calcineurin, Post Phagosome Formation in Mycobacterial Pathogenesis Science and Engineering Research Board (SERB)
Elucidating SOCS1 and CISH Mediated Dampening of IFNg Signalling During Mycobacterial Pathogenesis using Genome Editing Technologies ISIRD, SRIC
Identifying the Host Substrates for the Mycobacterial Virulence Factor Protein Kinase G, its Functional Characterization in Context of Mycobacterial Survival DEPARTMENT OF BIOTECHNOLOGY, MINISTRY OF SC. & TECH
Understanding the Metabolic Adoptation Leading to Chemoresistance in Leishmania Against Novel Drugs that Target Unique Prokaryotic TopA Homolog Indian National Science Academy
Area of Research: Infection Biology
Area of Research: Host-parasite interaction and therapeutics