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PhD In Psychological Medicine & Clinical Neurosciences - The impact of FAN1 on gene editing approaches for Huntington’s disease


Project Description

Huntington’s disease (HD) is an autosomal dominant disease that leads to neurodegeneration and death inexorably within 15 to 20 years. There is no disease modifying treatment available. An expanded repeated section of the huntingtin gene causes the disease and the larger the size of the repeated section the earlier the onset of disease. One way to treat HD is to use novel gene-editing methods to reduce the size of the disease-causing repeat in the genome. We can direct these gene-editing methods to the repeat to make it contract by cutting the DNA and removing a section. The cuts are then resealed by the usual cellular machinery that repairs DNA, which exists to maintain the stability of the genome in each cell. However, we do not understand the details of this gene-editing DNA repair mechanism - but we do know that variation in the DNA repair machinery, can itself affect the age at onset of HD. FAN1 is a member of the DNA repair machinery which acts to cleave DNA and usually repairs DNA interstrand crosslinks when cells divide. We intend to investigate how FAN1 and other molecules of the DNA repair machinery that are known to alter age at onset of HD interact with the gene-editing machinery and what effect that might have on the use of this technology as a therapeutic approach in HD. We will do this initially in cells carrying long repeats in their huntingtin gene themselves edited to carry variation in the DNA repair machinery and follow this up in animal models of disease. The impact of this project is two-fold. First, understanding how gene-editing leads to repeat contraction may help to make the potential treatment safer, more predictable and more efficient. Second, determining whether normal variation in the DNA repair machinery in people affects the treatment will allow us to identify early whether an individual is likely to benefit from such a therapeutic avenue.

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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