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  The role of splice variants in regulating BRCA1 function

   Cardiff School of Biosciences

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  Prof Matt Smalley, Dr Helen Pearson, Dr Guisy Tornillo  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Inheriting one mutant copy of the BReast CAncer 1 (BRCA1) gene (alongside one normal copy) is well-established as a strong risk factor for the development of breast and ovarian cancer. Moreover, inactivation of the BRCA1 gene, due to deletion, post-transcriptional deregulation or promoter hypermethylation, can be also detected in non-hereditary breast cancer. BRCA1 plays a critical role in many important cellular processes, including DNA repair, cell proliferation and transcriptional regulation.

BRCA1 is a highly alternatively spliced gene, but only a few of the BRCA1 alternative transcripts have been investigated functionally. There may be up to six normally expressed in humans and eight in dogs, while in tumours BRCA1 splicing is dysregulated and likely contributes to aggressive tumour behaviour. The alternative transcripts of BRCA1 can mimic known functions, possess unique functions compared with the full-length BRCA1 transcript, and in some cases, appear to function in opposition to full-length BRCA1. However, the exact roles of the various possible isoforms, how they are normally regulated and deregulated in cancer and whether they differentially affect the different BRCA1 DNA-repair and non-repair pathways remains to be defined. We would like to offer a project addressing:

- how BRCA1 alternative splicing may serve as an alternative mechanism for the inactivation of the BRCA1 gene in both hereditary and sporadic breast cancer

- whether alternative BRCA1 splicing pattern can be used as diagnostic and/or prognostic marker in breast cancer

Techniques: Cell culture; immunofluorescence/immunohistochemistry; western blotting; gene expression analysis by qrtPCR; CRISPR/Cas9; transfection; use of mouse, canine and human cell lines and tissue samples (no animal work)

Candidate requirements

A 1st or Upper 2nd class UK honours degree or equivalent. Please visit School of Biosciences Postgraduate Research for more details.

For those whose first language is not English, IELTS with an overall score of 6.5 with 5.5 in all subskills, or equivalent. Please see our English Language Requirements guidance for more details.

How to Apply 

To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy), Mode of Study (Full Time) and Start Date (this can be flexible as it is a self-funded project). This will take you to the application portal.

Candidates must submit the following:

 • Supporting statement

 • CV

 • Qualification certificates

 • Proof of English language (if applicable) 

In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, specify that you will be self-funding. If you are applying for more than one Cardiff University project with the same entry intake, please note this in the research proposal section as the form only allows you to enter one title.

Biological Sciences (4)

Funding Notes

There is no funding attached to this project, so students will need to source their own (tuition, bench fees if applicable, living fees if applicable).

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