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PhD in Cancer & Genetics - Targeting intestinal cancer using 3D organoid cell models


Project Description

Over one million new cases of colorectal cancer (CRC) are diagnosed worldwide each year. Inherited factors appear to be involved in up to 35% of cases. The genetic syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated polyposis (MAP), predispose to upper and lower gastrointestinal (GI) cancers with a near 100% lifetime risk of CRC. Clinical trials aimed at polyp burden reduction and cancer prevention in these patients have so far been unsuccessful. Current treatment for FAP and MAP patients involves radical colorectal surgery with lifetime upper GI surveillance. Studies of the natural history of these disorders is limited and molecular studies virtually non-existent.

The Inherited Tumour Syndromes Research (ITSR) Group recently completed the first exome and transcriptome sequencing studies in FAP and MAP colorectal and duodenal adenomas (Rashid et al, 2016, Thomas et al, 2017) providing insights into the drivers and mutational landscapes of these tumours. This studentship will build upon this characterisation, targeting established and putative drivers of duodenal and colorectal tumorigenesis to delineate targets for therapeutic interventions. To target established and putative drivers of tumorigenesis, this study will use pre-clinical 3D intestinal organoid models (’mini-guts’) derived from tissues from FAP and MAP patients in combination with genome editing technologies (including CRISPR-cas9) and drug repositioning studies. The student will also contribute to parallel international prospective studies of the natural history of duodenal disease, determining the age-related incidences and progression of adenomas and cancers and the effectiveness (or otherwise) of current treatments. The combination of laboratory genetic research and clinically oriented research will provide the opportunity to understand the translational opportunities and challenges of cancer genetic research.

This studentship will be undertaken in the Cancer Genetics Building, Heath Park Campus, within the Division of Cancer and Genetics. The student will be embedded within the ITSR Group, headed by Prof Julian Sampson, under the direct supervision of Dr Laura Thomas and Dr Hannah West, experienced research fellows within the ITSR group and Dr Karen Reed an experienced researcher and Wales Gene Park Operations manager. One of the strengths of the host laboratory is the mixture of basic scientists with broad research experience; PhD students and clinicians undertaking research together. The group has an excellent and sustained publication record on the genetics of polyposis, with papers in Nature Genetics, the Lancet, JNCI, Gastroenterology and Gut. This highly supportive environment enables students to develop their own ideas to achieve their research aims, whilst receiving training in all required aspects.

Working with established national and international collaborations will ensure the global context of medical research is understood. The ITSR group will support attendance and presentation at international conferences including Insight, CGA, EHTG and ESHG. There will also be opportunities for formal internal and external training including high-performance computing at Cardiff University (ARCCA), and a short-term residential bioinformatics course at Wellcome Trust Sanger Institute. Additionally, outreach opportunities and STEM ambassador registration will be encouraged.

Funding Notes

The studentship is generously funded by the School of Medicine
Full UK/EU tuition fees
Doctoral stipend matching UK Research Council National Minimum
Additional funding is available over the course of the programme and will cover costs such as research consumables and training.
Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

References

In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the system click 'Apply Online' at the bottom of this advert)
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2019). This will take you to the application portal.
Candidates are only permitted to submit one application but may select a maximum of three projects, ranked in order of preference in the ‘Research Proposal’ section of the application. In order to be considered candidates must submit the following information:

• Supporting statement
• CV
• Qualification certificates
• References x 2
• Proof of English language (if applicable)

Related Subjects

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