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.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Genetics, biochemistry or Molecular Biology. Candidates with experience in Gene Expression analysis or with an interest in RNA processing are encouraged 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 PhD Genetics.
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. For more information please visit
http://www.internationalphd.manchester.ac.uk
