Research SummaryRole of RNA binding proteins in Hedgehog signalling
Hedgehog (Hh) signalling is one of the most studied signalling pathways and yet remains the most enigmatic of all. Its components were first identified in searches for embryonic lethal mutations in Drosophila. Other signalling components were identified via several screens that followed later. Intriguingly, an in vitro screen identified several RNA binding proteins. These proteins may have a role in the splicing of Hh pathway components and mRNA transport. However, these proteins seem to play a more direct role in this pathway.
Two RNA binding proteins are known to regulate Hh signalling. Interestingly, they were not picked up in any RNAi screen done earlier. Likewise, there may be many more that missed the in vitro screens due to inherent experimental shortcomings.
With this background, I propose to:
1. Screen for other RNA binding proteins in vivo.
2. Confirm the candidates picked up in the screen.
3. Analyse most interesting genes for their epistatic interactions with components of the Hh pathway.
4. Employ biochemical methods to further characterise the proteins.
This will shed light on the puzzling role of these pleiotropic proteins in the regulation of Hh pathway.