The BBSRC UK-India projects are funded through a £13M India-UK Collaboration in Farmed Animal Health and Disease. Of the 12 projects recently selected for funding, three are based at University of Glasgow and two are focused on Theileria annulata, an important tick-borne protozoan parasite of ruminants.
Hsp90 as a modulator of pathogenicity, virulence and transmission in veterinary infections caused by Theileria and Babesia species
is a joint grant between Eileen Devaney, and Brian Shiels University of Glasgow, with Utpal Tatu, at Indian Institute of Science, Bangalore. The project aims to understand to role of the molecular chaperone Hsp90 in the life cycle and pathogenicity of T. annulata and Babesia spp. It brings together scientists with significant expertise in many aspects of parasite biology (Professor Shiels) with those with experience of biochemical, structural and functional aspects of Hsp90 (Professors Tatu and Devaney).
In India alone, losses due to T. annulata infection are estimated to be in the region of $400 million per annum. Studies in other apicomplexan parasites have demonstrated an essential role for Hsp90 in differentiation, infection and virulence. Hsp90 is a well-characterised molecule in many other systems and importantly many specific small molecule inhibitors are available. T. annulata infected cells adopt several characteristics of tumour cells (uncontrolled proliferation, ability to metastasize) and, as Hsp90 plays an important role in many cancer cells in maintaining the transformed phenotype, we believe that it may hold the key to understanding the pathogenicity of Theileria infection. In addition, the availability of small molecule inhibitors of Hsp90, designed for use in tumours, offers the potential for repurposing of these compounds to important infections of livestock. T. annulata expresses four isoforms of Hsp90, a classical cytoplasmic, an ER, an apicoplast and a mitochondrial form. Out emphasis is on understanding the function of the classical cytoplasmic form with a particular emphasis on the possible role of secreted Hsp90.