Dissecting the molecular mechanism of translation initiation*
Colin Aitken (Biology)
Translation initiation represents one of the most important readings of the genetic code, and affords cells the opportunity to control gene expression in response to cellular demands and external stimuli. The misregulation of translation initiation has been implicated in myriad human diseases, including cancer and neurodegenerative disease. Eukaryotic initiation factor 3 (eIF3) is the largest and least understood of the initiation factors that guide this process; it has been implicated in events throughout the initiation pathway and beyond. We will focus on dissecting the roles of eIF3, using genetic, biochemical, and next-generation sequencing approaches to interrogate its molecular mechanism. In particular, we will concentrate on further understanding the role eIF3 plays in loading the mRNA to be translated onto the ribosome. To this end, we will attempt to express and purify recombinant eIF3 from bacterial cells, enabling us to make specific mutations in eIF3 — guided by recent high-resolution structural models — and then observing the effects of these mutations within a yeast in vitro reconstituted system and potentially at the whole genome level. Students working in the lab will gain experience with molecular biology, protein expression and purification, biochemical and biophysical approaches, and next-generation sequencing tools.
Prerequisites: Introductory biology and either one of the following 200-level courses (BIOL 218, BIOL 238, BIOL 244, or BIOL/CHEM 272) OR previous laboratory experience.
How should students express their interest in this project? Interested students should write briefly in their application why they are interested in this project, and describe any previous experience that might particularly prepare them for it. After reviewing the applications, I will contact short-listed candidates about setting up an interview. Students should not contact me directly.