Although transcription is the first step in eukaryotic gene expression, many post-transcriptional events determine the final fate of RNA molecules and impose additional complexity to gene expression. Current models suggest that mRNAs that encode functionally related proteins are co-ordinately regulated as post-transcriptional RNA operons (or regulons) through the formation of highly regulated
RNA-protein complexes. Indeed, RNA-binding proteins (RBPs) can act as master regulators of gene expression by binding groups of functionally related mRNAs. Importantly, defects in RBP function cause a variety of pathologies ranging from cancer to muscular, neurological, metabolic, haematologic or immunological diseases. The aim of this project is to investigate in vivo the mechanisms used by conserved RBPs in the regulation of stem cell identity and cell differentiation. You will use the Drosophila adult mid-gut – a sophisticated model for the regulation of intestinal homeostasis – to investigate how conserved RNA-binding proteins regulate the balance between self-renewal and differentiation, and the appropriate proportions of the different mature cell types that populate and maintain the functionality of the gut. First, you will perform a genetic and functional screen to identify RBPs involved in the regulation of adult stem cell identity and differentiation, both under physiological conditions as well as under stress. Then, you will use stateof the art genomic approaches to identify the RNA molecules associated with the relevant RBPs. Finally, you will combine genetic in vivo approaches (e.g. loss-offunction, gain-of-function or epistasis studies) and biochemical/molecular approaches (e.g. characterisation of the RNA-RBP interactions) to characterize in vivo the molecular mechanisms used by RBP to regulate stem cell function.
The originality of this project is to focus on the potential of RNA regulation, rather than signalling and transcription, as a determinant of cell behaviour. It has the potential to define new and exciting research questions and will offer an excellent training opportunity to the student in stem cell and developmental biology, microscopy and histology, molecular biology and NGS methods.
This studentship is available to UK and EU nationals who have established UK residency (EU nationals must have ordinarily lived in the UK throughout the three years preceding the start of the studentship). Please refer to the DTP eligibility webpage for more details: https://www.swbio.ac.uk/programme/eligibility/
Cardiff University will be able to award up to one fully funded four-year studentship for EU students who do not meet the residency requirements.
Please refer to the DTP eligibility webpage for academic entry requirements: https://www.swbio.ac.uk/programme/eligibility/
If English is not your first language, you will need to achieve an IELTS score of 6.5 with 6.5 in all skills.
How to apply
Make your application to Cardiff University: https://www.cardiff.ac.uk/study/postgraduate/applying/how-to-apply
Please ensure that your application includes:
Two references. Neither of the referees should be part of the supervisory team.
Academic transcripts / degree certificate(s)
Personal statement. Please include supporting evidence for your Maths background.
Curriculum Vitae (CV)
English language certificates (where applicable)
Please refer to the DTP webpage for information about the selection process: https://www.swbio.ac.uk/programme/selection-process/
Applications must be submitted by midnight on Monday 2nd December 2019.