Elucidating the mechanism of the first round of mRNA translation
Supervisor: Dr Timothy Weil
This project aims to understand the molecular mechanisms leading to the first round of mRNA translation. This is a fundamental question in biology since controlling the initiation of translation is essential in all cells.
To explore this, we examine the oocyte-to-embryo transition in Drosophila to enable research in an in vivo context, an approach that has been under-investigated. Using in vivo techniques that have been established in the Weil Lab, this project offers a unique, unparalleled approach at resolving the fundamental question of how cells regulate protein production spatially and temporally. First experiments would include assaying translation with the novel RNA biosensor (TRICK system) for imaging the first round of mRNA translation in different genetic backgrounds and under specific experimental conditions. To identify proteins associated with control before and after translational activation in wild type and mutant mRNAs various biochemical approaches will also be undertaken. These data will identify key proteins that mediate changes in translational activation to then be observed in vivo. This approach will build on exciting data linking the dispersion of Processing bodies, conserved cytoplasmic regions of mRNA regulation, to the activation of translation.
The control of initiation of protein synthesis allows cells to orchestrate changes with exquisite sub-cellular and temporal precision thus making it a cornerstone of cell biology. Translational regulation is crucial and misregulation of mRNA function has a role in developmental defects as well as neurodegenerative and genetic diseases. Therefore, the results of this project are likely to shed considerable light on the basic processes underpinning both cell biology and disease.
An RNA biosensor for imaging the first round of translation from single cells to living animals.
Halstead JM, Lionnet T, Wilbertz JH, Wippich F, Ephrussi A, Singer RH, Chao JA.
Science. 2015 Mar 20;347(6228):1367-671.
Drosophila patterning is established by differential association of mRNAs with P bodies.
Weil TT, Parton RM, Herpers B, Soetaert J, Veenendaal T, Xanthakis D, Dobbie IM, Halstead JM, Hayashi R, Rabouille C, Davis I.
Nat Cell Biol. 2012 Dec;14(12):1305-13.
Post-transcriptional regulation of embryogenesis.
F1000Prime Rep. 2015 Mar 3;7:31.