UTPAL S. TATU
      Professor

Ph.D.
Indian Institute of Science, Bangalore, India. 1991

Postdoctoral Research
Cell Biology, Yale University School of Medicine, U.S.A. 1991-1997

Research Interests
Biology of molecular chaperones, Malaria, Proteomics

My research aims to decipher the functions of molecular chaperones in cellular context. Chaperones are well known for their ability to assist protein folding, facilitate protein assembly, prevent protein denaturation and renature misfolded proteins. Biochemical activities and molecular mechanisms of chaperone function have been elegantly studied by reconstituting purified components outside the cell. However the broader impact of chaperone function in cell growth and development is only beginning to be appreciated.

A. Neglected infectious diseases:

1. Malaria

It is well known that the parasite experiences a temperature shock of over 10C during its entry in the vertebrate host. Furthermore, during febrile episodes in the patient the parasite is exposed to a heat shock (up to 41C) due to rise in the body temperature of the host. How does the parasite react to these rapid temperature fluctuations? What are the protective mechanisms employed by the parasite to counter cellular damage? Experiments performed in my group in the last 10 year have shed some light on these mechanisms.

Using biochemical, cellular as well as proteomic approaches we have characterized the expression, localization and complexes of abundant chaperones of the class Hsp40, Hsp60, Hsp70, Hsp90 and Hsp100 expressed by the parasite in human red blood cells. Our studies show an essential role for Hsp90 of the parasite and implicate it as a potential drug target against malaria. Pharmacological inhibitors specific to Hsp90 are currently being examined as candidate drugs against malaria.




The red blood cells undergo extensive remodelling during the course of infection. The cytosol of RBC acquires number of membranous compartments such as Maurers clefts and the cell membrane undergoes modifications to form protrusions know as knobs on its surface. Knobs make erythrocytes rigid and cytoadherent and are largely responsible for the severity of the disease. To bring about these changes parasite exports multiple proteins into the host cell. It is a challenging task for the parasite as it resides in a vacuole inside the RBC and the proteins need to transverse multiple membranes in order to reach their final destinations. It is being speculated that this process of protein trafficking requires an intricate involvement of chaperones owing to their ability to fold, unfold and stabilize proteins. Also, the exported proteins (especially the components of knobs) have a tendency to remain in a disordered conformation due to the presence of homorepeats and prion-like domains in their primary structure. A major group among the class of exported proteins is constituted by chaperones and surprisingly all of them belong to the Hsp40 family. We are interested in understanding the specific roles played by these Hsp40s in the process of host cell remodelling. Towards this, we have generated antisera against some exported Hsp40s and carry out in vivo experiments involving immunofluorescence and immunoprecipitation analysis to determine the localization and interacting partners of the protein respectively.

Surra is caused by Trypanosoma evansi infection. It is a veterinary protozoan disease most common in the cows, buffaloes, horses and other cattle. My laboratory works on understanding the role of chaperone in the progress of disease in host. The disease has been listed as one of the major concern by OIE in 2011. This is disease common in tropical countries. And my group focuses on understanding the chaperone biology in the progress of this disease in animals.

Heat shock protein 90 plays diversified roles in different microbes. Like any other pathogen Giardia lamblia also uses heat shock protein machinery to survive under stress full conditions put forth by host. In this particular microbe m-RNA coding for Hsp90 arrives from a unique split gene conditions. The research done at my neglected disease lab on giardiasis inferred that the full length Hsp90 in Giardia lamblia is produced by a transplicing mechanism occurring inside Giardia lamblia. We constantly work on deciphering the truth behind this mysterious and unique feature of producing Hsp90 protein in Giardia lamblia.

In context to a neglected disease conditions my lab has taken over studying the importance of Hsp90 in Entamoeba histolytica. The microbe is responsible for a most common clinical problem called as amoebiasis. My lab works on understanding the role of heat shock proteins in this pathogen while tissue/ luminal/ liver infections.

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.

Going further to understand the complex cellular functions of heat shock protein 90 my lab also focuses on the understanding of this biochemical machinery in relatively simple micro organism model systems like Dictyostelium and Saccharomyces. We have been constantly unravelling the facts about role of cytosolic isoform of Hsp90 called as HspD in D. discoideum development using various molecular biology and proteomics tools. Interestingly the crystal structure of N-terminal HspD showed similar binding pocket for yeast Hsp90. Our studies show cellular slime mold to serve as effective cellular model to study Hsp90 at cellular and organism level.

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.

In addition to the quest of understanding the chaperone biology in infectious and neglected diseases we constantly focus on the translational/application sciences by using 2DGE, mass spectrometry and bioinformatics analysis which ultimately culminates into leading proteomics research out comes in the country. 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 clinical proteome of Plasmodium falciparum, Plasmodium vivax infections.