Identification of the active eIF4E in trypanosomes (360G-Wellcome-207062_Z_17_Z)

A detailed understanding of the initiation of translation in kinetoplastid pathogens is still elusive. There is an innate complexity due to the number of isoforms of eIF4E and eIF4G, two of the three components of eIF4F. Second, there has been no simple way to rapidly ablate expression of a protein to render an immediate phenotype. RNAi is available but it takes 3 to 4 cell cycles to dilute the eIF4E sufficiently to detect a phenotype and then is difficult to distinguish primary and secondary phenomena. We have recently developed a system for the inducible ablation of a specific protein in less than 60 minutes. This summer studentship will exploit this method to ablate separately the two isoforms of eIF4E that probably are responsible for mRNA cap binding during translation initiation. An analysis of the qualitative and quantitative effect on protein synthesis after ablation will inform on whether the two eIF4E isoforms have different, overlapping or identical functions. The work builds on expertise in the lab and utilizes a new technique to answer a long standing question.