Regulation of gene expression in African Trypanosomes. (360G-Wellcome-077716_Z_05_Z)

Trypanosoma brucei is the causative agent of sleeping sickness in man and Nagana in cattle. One interesting aspect of trypanosome biology is the almost complete absence of transcriptional control, which is the major control point for regulating gene expression in most eukaryotes. Therefore it would not be surprising to identify novel mechanisms of post-transcriptional gene regulation exemplified in these organisms that are important but subtle in other eukaryotes. Understanding this fundamental aspect of trypanosome biology may reveal an Achilles heel in these pathogenic parasites. My genome wide survey of the 2004 completed T.brucei genome sequence suggests that the novel CCCH zinc finger family of proteins, that has been implicated in post-transcriptional regulation of gene expression via RNA binding, may be of great importance in trypanosomes. This project will define the lifecycle specific expression pattern, cellular consequences of perturbed expression, cellular localisation and mechanism of RNA binding for 4 selected T.brucei CCCH proteins. One of these will be prioritise for further dissection via more detailed processing analysis and expression profiling. This will determine the regulatory extent and cellular function(s) of these novel CCCH proteins and indicate the significance of the CCCH family of proteins in T.brucei regulated gene expression.