Gene expression regulation by RNAbinding proteins during fly development

Although the first steps in eukaryotic gene expression are nuclear, many post-transcriptional events determine the final fate of RNAs 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 RNAprotein complexes. Indeed, RNAbinding proteins can act as master regulators of gene expression by binding groups of functionally related mRNA. Importantly, defects in RNAbinding proteins cause a variety of pathologies ranging from cancer to muscular, neurological, metabolic, haematologic or immunological diseases.
Using Drosophila as a model system and a variety of techniques, our group seeks to identify and functionally characterize in vivo mRNAs sharing similar regulatory networks. Particularly, we are interested in understanding the cellular and developmental roles of the Polypyrimidine Tract Binding Protein, PTB. PTB belongs to the heterogeneous nuclear ribonucleoprotein family (hnRNP) of proteins, which associate with transcripts as they are synthesized and control multiple aspects of RNA processing, both in the nucleus and cytoplasm. However, it is still not clear how hnRNP proteins discriminate among multiple RNA targets and most importantly, the mechanisms they use to regulate specific RNA targets.
To understand the mechanisms of action of PTB, we have performed a yeast two-hybrid screen and identified potential new PTB-interacting partners. The results of our screen support a model in which PTB forms distinct complexes in: a) the cell cytoplasm, to regulate functionallyrelated mRNAs in association with other RNA-binding proteins; and b) in the nucleus, to regulate not only premRNA splicing, but also likely chromatin structure and nuclear transcription.
This project is aimed at characterizing, both molecularly and functionally, these distinct PTBcontaining complexes. To start defining their composition, the student will compare the in vivo subcellular distribution of PTB and its binding partners in different fly tissues. S/he will then use genomewide approaches to identify: 1) RNA molecules associated with PTB and their binding partners, and 2) chromatin regions bound by PTB complexes. Finally, the student will use a variety of fly genetics tools to study the in vivo function of different PTB complexes.
We believe this is an exciting project as it has the potential to define new and exciting research questions, and will offer an excellent training opportunity to the student.

The SWBio DTP follows a 4-year PhD model. In the first year, you will receive a range of directed training, tailored to support your PhD project. This includes a series of compulsory taught units (taught co-localised) and self-directed study that take up about one-third of your available time. In addition, you will experience two assessed laboratory rotations in year 1, each in separate disciplines but designed to provide focused training tailored to your PhD project. You will be able to use your experiences with the laboratory rotations to refine the PhD project on which you will concentrate on from August of the first year. The PhD thesis must be submitted within 4 years of starting the programme.

Academic criteria
Applicants for a studentship 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. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in the projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required.

Equivalent qualifications/experience
•Physics A-level (grade B and above)
•Undertaking units as part of your degree that have a significant mathematical component*
*Significant mathematical component examples include; maths, statistics, bioinformatics.
Applicants are required to highlight their Maths background within their application and must upload supporting evidence.
If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.