Is the skin the site of a human reservoir in African trypanosomiasis? (360G-Wellcome-095201_Z_10_A)

The aim of this project is to examine the role of natural genetic variation in both the human host and parasite in determining the outcome of infection with either T.b. gambiense or T.b. rhodesiense. There is now a body of data, which shows there is variation in the factors that: (a) prevent initial host infection; and (b) determine disease severity. However, we have a relatively limited knowledge of the mechanisms involved and how genetic variation affects disease outcome. This proposal will ex ploit natural genetic variation to identify the key features and molecules involved using a combination of host association of candidate genes, parasite population genomics and molecular analysis of trypanolytic complexes present in serum. In addition, the proposal will create a large genomic sequence resource of > 140 parasite strains together with a biobank of the parasites strains for those working in other areas. Thus, by dissecting some of the key components of both host and parasite which are determinants of infection and disease outcome, a series of pathways and molecules will be identified which could be the targets of novel interventions aimed at preventing or controlling the disease