BBSRC SWBio DTP PhD studentship: Investigating conserved long non-coding RNA functions during neural crest cell self-renewal and melanocyte development in zebrafish

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP) which is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bath, Bristol, Cardiff and Exeter, along with the Rothamsted Research Institute. The partnership has a strong track record in advancing knowledge through high quality research and teaching, in collaboration with industry and government.

Studentships are available for entry in September/October 2018.

All SWBio DTP projects will be supervised by an interdisciplinary team of academic staff and follow a structured 4-year PhD model, combining traditional project-focussed studies with a supporting but focussed taught first year with directed rotation projects.

Supervisory team:
Main supervisor: Dr Keith Vance (University of Bath)
Second supervisor/s: Prof Robert Kelsh (University of Bath) and Prof Mark Lindsay (University of Bath)
Collaborators: Dr Karim Malik (University of Bristol)

The vertebrate genome expresses many thousands of long non-coding RNAs (lncRNAs). Although it remains to be determined whether the majority of these are functional, a growing number of lncRNAs have been shown to act as gene expression regulators with proposed roles in the control of numerous fundamental biological processes. However, most studies investigating lncRNA action have been performed using cells in culture. It is therefore of key importance to disrupt lncRNA function in animal model systems to identify and characterise the regulatory roles played by lncRNAs during development in vivo. During development, neural crest cells give rise to a number of different cell types including pigment producing melanocytes. Accumulation of DNA mutations within melanocytes during the lifetime of an individual can give rise to melanoma, a highly aggressive form of skin cancer. Accordingly, many of the genes involved in melanoma also function in the control of melanocyte development whilst re-expression of neural crest cell gene expression programmes in a subpopulation of melanocytes is a key early event driving the development of melanoma.

In this project, we will use zebrafish as a model system to investigate the function a prioritised subset of conserved human-zebrafish lncRNAs in melanocyte development in vivo. We will perform RNA-sequencing to assemble a catalogue of lncRNAs that are expressed in purified zebrafish neural crest cells. Computational methods will then be used to compare these zebrafish lncRNAs with human melanoma associated lncRNAs and identify a subset of orthologous transcripts that are expressed from equivalent regions of the zebrafish and human genomes. CRISPR interference will be performed to deplete the expression of selected lncRNAs in neural crest cells in zebrafish and determine the role of these lncRNAs during neural crest cell differentiation and melanocyte development in vivo. LncRNA regulated gene expression changes will then be characterised using RNA-sequencing and orthologous human lncRNAs will be used to attempt to rescue zebrafish phenotypes and identify conserved lncRNA functions in development. This work will generate important insights into lncRNA mediated mechanisms of cellular growth and differentiation control during melanocyte development and will have implications for understanding the role of lncRNAs in melanoma.

Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree (or the equivalent qualifications gained outside the UK) in an appropriate area of science or technology. In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in SWBio DTP projects, a minimum of a grade B in A-level Maths (or an equivalent qualification or experience) is required.

Candidates should apply using the University of Bath’s online application form selecting PhD programme in Biosciences (full-time) https://www.bath.ac.uk/study/pg/applications.pl#bio-sci

For more information, please see: http://www.bath.ac.uk/science/postgraduate-study/research-programmes/funding/bbsrc-phds/