Interaction of orthologs of alba, RanBP and other ligants to TOR in Trypanosoma

• Grant number: 13/02629-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2013
• End date: January 31, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Schenkman
• Grantee: Jethe Nunes de Oliveira Filho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/51973-3 - Cell signaling mechanism of Trypanosoma in response to nutritional alterations and genotoxic agents, AP.TEM

Abstract

Protein kinases named TOR (Target of Rapamycin) act as protein complexes with key functions in the control of cellular division and cellular growth. Trypanosomes have four genes encoding this type of kinase. One of them, which is involved in osmotic stress responses, has a PDZ domain, not found in other eukaryotic TORs. In two-hybrid assay we have previously identified ligands for this domain. In this project we intend first to biochemically validate these interactions, test whether they also occur in Trypanosoma brucei, and find out their role during TOR signalling. The interaction will be conformed by two-hybrid, co-immunoprecipitation and colocalization in before and after osmotic stress. In parallel, we will identify the interactions of the identified ligands by tamdem affinity chromatography. These studies will allow to understand how trypanosomes respond to environment changes, information useful to develop new drug targets for this group of organisms, agents of several parasitic diseases. (AU)