Molecular Dissection of CCCH ZFPs - Gatekeepers of the African Trypanosome Genome. (360G-Wellcome-080403_Z_06_Z)

This project aims to investigate the roles of the Trypanosoma brucei CCCH zinc finger proteins (CCCH ZFP) as novel regulators of gene expression. The ultimate goal is to understand the unusual mechanisms utilised by trypanosomas to regulate gene expression and use these as fundamental targets for anti-parasitic drugs. Specifically this proposed research will: i) Define if two CCCH ZFPs (denoted TbC3H43.7/49.6) are essential for controlling T.brucei lifecycle progression and the contribution of the CCCH motifs within TbC3H43.7/49.6 as functional determinants for trypanosome cellular development. ii) Determine if there is a functional relationship in cell development between TbC3H43.7/49.6 and any phosphorylation-dependent protein pathways. iii) Identify the RNA binding capacity and specific RNA targets of TbC3H43.7/49.6 as the putative mechanism of post-translational control of gene expression. iv) Analyse the specific targets of TbC3H43.7/49.6 for their role in differentiation using established assays (over-expression or RNAi) on transgenic parasites generated in BS cells. v) Use a CAT reporter system to define any interacting RNA sequences governing mRNA stability.