Targeting the surface proteome of Trypanosoma cruzi

• Grant number: 14/50824-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2015
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Agreement: CONFAP ; Newton Fund, with FAPESP as a partner institution in Brazil ; MRC, UKRI
• Principal Investigator: Sergio Schenkman
• Grantee: Sergio Schenkman
• Principal researcher abroad: Mark C. Field
• Institution abroad: University of Dundee, Scotland
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The surface of protozoan parasites represents the interface with the host, and plays roles in invasion, immune evasion, signaling, and more. We recently identified a conserved ubiquitylation pathway in African 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 proteins in this parasite to assess their importance to host cell invasion and virulence. This application seeks to assess the importance 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, specifically trans-membrane domain proteins and their impact on the global surface proteome; 3) Possible value as a therapeutic target the work will combine state of the art genome editing using CRISPR/Cas approaches, together with SILAC proteomics for unbiased analysis of the surface cellular proteome. (AU)