My research

Postdoc Research

PhD Research

During my PhD, I investigated the function of Heat Shock Protein 90 (Hsp90) in the life cycle and virulence of parasitic protozoa. Among molecular chaperones, Hsp90 is unique in that its functions extend beyond protein folding. Hsp90 is present as a part of a multichaperone complex, which includes various co-chaperones.

New Hsp90 co-chaperone, Singh et.al. 2014

These co-chaperones regulate and aid in Hsp90 function. Early branching protozoa possess only a partial co-chaperone repertoire lacking many conserved cochaperones. Using three early-branching protozoa parasites- Entamoeba histolytica, Trichomonas vaginalis and Theileria annulata, I addressed specific questions pertaining to the evolution of the Hsp90 multichaperone complex, its unique features, cellular functions and regulation by a novel co-chaperone. Using biochemical, cell biology and proteomics approaches I studied the properties and function of Hsp90 of Entamoeba, Trichomonas and Theileria and showed they have a higher affinity to Hsp90 inhibitors than the host as they differ in their biochemical properties despite the high similarity. I also show that Hsp90 is essential for proliferation and specifically regulate stage transition and phagocytosis in Entamoeba.

Hsp90 regulates phagocytosis in Entamoeba, Singh et.al. 2015

In collaboration with structural biologists, we identified a novel peptide inhibitor of Hsp90. Secondly, I focused on the evolution of the Hsp90 multi-chaperone complex. I identified a novel co-chaperone, EhAha1c in Entamoeba which enhances its ATPase activity. Lastly, I identified Hsp90 homolog, TV910, in the genome of this parasite which lacked the canonical ER retention motif.  I showed that TV910 is secreted by the parasite via the classical secretory pathway and was the first report of Hsp90 secretion in parasitic protozoa. Overall, I showed that Hsp90s from early-branching protozoa differ from higher eukaryotes in terms of their biochemical and cell biological properties. 

Hsp90 peptide inhibitor (Raman, Singh et.al. 2015)

Secreted Hsp90 in Trichomonas vaginalis. Singh et.al 2018