In vitro analysis of the molecular basis of strain variation in scrapie
Funded by BBSRC-DTA
Associated scientist: Mr. James Graham, Dr Louise Kirby and Dr Andrew C. Gill
TSE strains are associated with characteristic differences in neuropathology, incubation times and extent of glycosylation of the PrPC protein. Different strains can be stably passaged in isogenic hosts indicating that the primary sequence of the PrP protein is not responsible for strain variation. It has been suggested that different strains are encoded by different conformations of PrPSc, the abnormal prion protein isoform. We believe that this structural diversity is aided by accessory molecules, or co-factors, that aid strain-specific misfolding. This project takes a dual approach to identify potential strain-specific co-factors. One approach involves the sub-cellular fractionation of TSE-susceptible cell lines to produce pools of molecules that may contain co-factors. A second approach involves the analysis of PrPSc deposits for the presence of molecules other than PrPSc, which could also be accessory molecules. To test whether molecules function as co-factors, we have misfolding assays including an in vitro, cell free conversion assay and PrP oligomerisation assays.
More details: please contact Andrew C. Gill