Project No. 2317
Dr Susanne Dietrich – University of Portsmouth
Dr Matthew Rose-Zerilli – University of Southampton
Dr Frank Schubert- University of Portsmouth
Bmp and Fgf signalling molecules control cell fate choices, proliferation and differentiation during embryonic development, tissue/organ maintenance and disease.
The Schubert/Dietrich teams have conducted an RNAseq screen for Bmp- and Fgf-dependent genes in the head of early chicken embryos at the time the first neurons, the heart, the cranial vasculature and the foregut form. The chicken embryo is a recognised model for vertebrate development; it was chosen for its large size, accessibility, ease of manipulation, and because it complies with the 3Rs principle. In this screen, we identified novel genes so far not associated with development or Bmp/Fgf signalling. A significant proportion of these genes account for non-coding RNAs which recently emerged as a new class of regulators. Expression and function of our new genes are not known.
Here, we will use bioinformatic analyses to identify which of the novel genes are phylogenetically conserved and hence likely play fundamental roles in Bmp and Fgf signalling. We will use the bioinformatics pipeline in the Rose-Zerilli lab to interrogate the publicly available single-cell RNA sequencing datasets to associate the novel genes with cell types, differentiation states and biological processes. We will in the Dietrich lab establish the expression of these genes using in situ hybridisation; this will be facilitated by the chicken EST library we recently obtained from Source Biosciences. We will treat embryos with Bmp, Fgf or pharmacological inhibitors to validate Bmp/Fgf-dependency. Finally, we will exploit the expertise of the Portsmouth -based European Xenopus Resource Centre to establish gene function using Crispr-Cas.
The work will deliver entirely new cellular regulators and will provide novel insight into the mechanisms of Bmp- and Fgf-mediated cellular decisions.
The candidate for this project needs a sound understanding of cell/developmental biology and be keen to learn embryo/tissue micromanipulation as well as Unix and R-based coding.