Analysis how de novo mutations in an RNA splicing regulator change global gene expression patterns

Male infertility is a very widespread medical problem, but the actual biology of normal fertility is very poorly understood. Recently human genetics has identified mutations within genes that are expressed all over the body that cause male infertility. What effect these mutations have on cell function is not known. In this project we will use genome engineering and bioinformatics analyses to answer this question. We have a clue already: some of the heterozygous mutations are in genes encoding splicing regulator proteins, meaning that they most likely change patterns of gene expression. These mutated genes include a gene encoding an important splicing regulator called RBM5 (this particular splicing regulator is also implicated in lung cancer). Splicing is important since almost every human gene is split into exons and introns. This means that exons have to be spliced together to produce functional mRNAs that encode protein. Proteins like RBM5 regulate this splicing process, so can have a huge impact on how genes function (for example in lung cancer levels of RBM5 protein control whether particular genes operate as oncogenes or tumour suppressors). The big questions we want to answer is to what extent and how these newly discovered point mutations in RBM5 change patterns of gene expression in cells. This project will provide the student training in genome engineering and global bioinformatics analyses, and so will place them in a very competitive position in the job market.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2^nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9^th January 2023.