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About the Project
The DNA of a cell is copied into a pre-messenger RNA (pre-mRNA) that the cell uses as a template for protein production. Some of the information contained in DNA is not required for making proteins, therefore, unwanted information must be removed before a protein is made. This unwanted information is removed, or spliced, from pre-mRNA by a process similar to the editing of unwanted frames from a film. This splicing of the pre-mRNA is very important because it must occur accurately in order for functional proteins to be produced. Splicing at the wrong position could have disastrous effects on the final protein produced. Mistakes in splicing could cause defects in the development of an organism or result in disease.
Pre-messenger RNA splicing is carried out by the spliceosome, a large RNA/protein complex composed of five small nuclear ribonucleoprotein particles (snRNPs). There are now ever increasing examples of mutations in snRNP proteins and other splicing factors being identified as the cause of diseases, including cancer. However, there is a lack of information on how these mutations influence the mechanisms of splicing and how this relates to the splicing events that are mis-regulated during the disease. We have identified mutations in a number of genes coding for snRNP proteins and splicing factors that cause specific diseases. However, it is unclear how these mutations affect splicing and cause the specific diseases. The project will use genetic, biochemical and molecular techniques to understanding the link between splicing factor gene mutation and splicing programmes that are disrupted to cause disease. This work will address a key fundamental question in bioscience for health which will have wide interest and impact.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
Eligibility
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 a relevant discipline. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team admissions.doctoralacademy@manchester.ac.uk
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
References
Thomas HB, Wood KA, Buczek WA, Gordon CT, Pingault V, Attié-Bitach T, Hentges K, Varghese VC, Amiel J, Newman WG, O’Keefe RT (2020) EFTUD2 missense variants disrupt protein function and splicing in Mandibulofacial Dysostosis Guion-Almeida type. Human Mutation. Apr 25. doi: 10.1002/humu.24027. Online ahead of print.
Wood KA, Rowlands CF, Qureshi WMS, Thomas HB, Buczek WA, Briggs TA, Hubbard SJ, Hentges K, Newman WG, O'Keefe RT (2019) Disease modelling of core pre-mRNA splicing factor haploinsufficiency, Human Molecular Genetics. 28(22):3704-3723. doi: 10.1093/hmg/ddz169
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