Utpal S. Tatu

Department of Biochemistry
Research Areas: 
Biology of molecular chaperones, Malaria, Proteomics
Research Highlights: 

My research aims to decipher the functions of molecular chaperones in a cellular context. We have several lines of research ongoing in the lab under these broad categories: (1) Malaria: Our studies show an essential role for Hsp90 in the survival of the malarial parasite when it is exposed to heat shocks and implicate it as a potential drug target against malaria. Pharmacological inhibitors specific to Hsp90 are currently being examined as candidate drugs against malaria. Another aspect of our research involves understanding how extensive remodelling occurs in red blood cells during the course of infection. We are trying to probe the specific roles played by the Hsp40 group of proteins in the process of host cell remodelling. Towards this, we have generated antisera against some exported Hsp40s and are conducting in vivo experiments involving immunofluorescence and immunoprecipitation analysis to determine the localization and interacting partners of the protein respectively. (2) Surra: Surra is caused by Trypanosoma evansi infection. It is a veterinary protozoan disease most common in the cows, buffaloes, horses and other cattle and is common in tropical countries. My laboratory works on understanding the role of chaperones in the progress of disease in host. We have shown important role of Heat Shock Protein 90 from T. evansi (TeHsp90) by using Hsp90 directed inhibitor called 17-AAG (17-allyl amino 17-demethoxy geldanamycin). We are now progressing towards starting animal trials against the disease using the above mentioned inhibitors. (3) Giardiasis: We have recently shown that Hsp90 in Giardia is arranged as a split gene, HspN and HspC separated by 777 kb intergenic sequence. The full length Hsp90 transcript is a resultant of a novel trans-splicing phenomenon which is mediated by spliceosomal complex. The mature full length transcript has all the hallmarks of the canonical Hsp90. The protein band that corresponded to a region of around 80 kDa was identified to be GlHsp90. Hence we provide evidence for such a reconstruction mechanism at proteomic level. Sequencing of the junctional peptide by MS/MS provides evidence of functional full length Hsp90 in Giardia, a novel approach to identify trans-splicing event using mass spectrometry. (4) We are also examining the importance of Hsp90 in Entamoeba histolytica. The microbe is responsible for a most common clinical problem called as amoebiasis. (5) Targeted drug discovery - While deciphering the novel molecular targets and pathways my group also uses anasamycin antibiotics as model organic molecules to understand the role of heat shock proteins in stress during the infection. (6) Other model systems - In addition to examining infectious protozoa, my laboratory also uses Dictyostelium discoideum and Saccharomyces cerevisiae to understand functions of Heat shock protein 90 and its co-chaperones in Biology. (7) Role of ER chaperones in protein folding - My group is also examining folding of secretory proteins in the ER of animal cells. By reconstituting the oxidative folding of retinol binding protein (RBP) in isolated ER we are examining the mechanisms underlying selective retention of apo forms of RBP in the ER. (8) Proteomic and bioinformatic activities. My group plays a leading role in mining the proteome data from the variety of biological exudates, coming directly from infected human/animal subjects by using state of the art proteomics and bioinformatics tools . We have successfully worked on the clinical proteome of Plasmodium falciparum and Plasmodium vivax infections.

91-80-2293 2823
  1. Grover, Manish, Shweta Chaubey, and Utpal S Tatu. 2013. Heat Shock Proteins As Targets For Novel Anti-Malarial Drugs. In Heat Shock Proteins of Malaria, Heat Shock Proteins of Malaria, Springer Science $\mathplus$ Business Media, 189–205. http://dx.doi.org/10.1007/978-94-007-7438-4_10.