Newton001: Targeting the surface proteome of Trypanosoma cruzi

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The surface of protozoan parasites represent the interface with the host, with many roles in invasion, immune evasion, signalling, and environmental sensing. We recently identified a conserved ubiquitylation pathway in trypanosomes that controls the surface copy number of important trans-membrane domain proteins, and which provides a means for the first time to manipulate trans-membrane domain protein abundance in these parasites in a rational manor, and to assess their importance to host cell invasion and virulence. This application seeks to assess the significance of the surface protein ubiquitylation pathway in Trypanosoma cruzi for: 1. Parasite viability, host cell invasion and life cycle progression,2. Maintenance of the surface coat, specificallycopy number of trans-membrane domain proteins and their impact on the global surface proteome, 3. Possible value as a therapeutic target, by assessment of viability in vitro.The work will combine state of the art genome editing using CRISPR/Cas9 approaches, together with SILAC proteomics for unbiased analysis of the surface/cellular proteome.