Genome editing for Duchenne muscular dystrophy

Teesside University is pleased to offer a fully funded PhD studentship to an exceptional doctoral candidate to commence in December 2024.

This studentship is funded by Muscular Dystrophy UK.

The National Horizons Centre in the School of Health & Life Sciences invites applications for a full-time PhD studentship in the following research area:

Genome editing for Duchenne muscular dystrophy

About this PhD project

National Horizons Centre, School of Health & Life Sciences

https://www.tees.ac.uk/nhc/

Director of Studies: Professor Linda Popplewell

https://research.tees.ac.uk/en/persons/linda-popplewell

Project description(s)

Microdystrophin gene addition therapy for Duchenne Muscular Dystrophy (DMD) has progressed through clinical trials with a conditional United States Food and Drug Administration (FDA) approval now in place. This therapy is however limited by its inability to restore all functional dystrophin domains, the uncontrolled expression resulting from the strong promoters used and the potential for transgene loss upon cellular division.

To combat these issues, we have developed novel and highly applicable CRISPR-Cas9 mediated genetic engineering strategies that would allow endogenous transcriptional regulation of expression and permanent transgene persistence in regenerating muscle. However, for a disease that has body-wide pathology, and a technology that has low efficacy, undesired consequences of targeted DNA cleavage repair and high risk of off-target editing, gaining approvals for clinical testing for any CRISPR-Cas9 genome edit are difficult to procure.

To address this, this project would focus on enhancing near-universal genome editing strategies for DMD through exploitation of a new CRISPR-Cas9 tool that removes the need for double strand break for the targeted integration, improves the efficiency of dystrophin transgene knock-in, and ensures applicability to non-dividing skeletal and cardiac muscle. After optimisation, proof-of-concept studies to establish permanent CRISPR/Cas9-mediated integration of sequence optimised dystrophin cDNAs into targeted DMD intronic sites in appropriate models will be performed, utilising high technological assessments to gauge efficacy.

Funding eligibility

This fully funded PhD studentship covers tuition fees for the period of a full-time PhD registration of up to four years and provide an annual tax-free stipend of £18,622 for four years, subject to satisfactory progress. The stipend will increase each year.

This studentship is only open to applicants who will pay UK fees.

Entry requirements

Applicants should hold or expect to obtain a good honours degree (2:1 or above) in a relevant discipline. A master’s level qualification in a relevant discipline is desirable, but not essential, as well as a demonstrable understanding of the research area.

How to apply

Applicants should apply online for this opportunity at:

https://e-vision.tees.ac.uk/si_prod/userdocs/web/apply.html?CourseID=1191

Please use the Online Application (Funded PHD) application form. When asked to specify funding select ‘other’ and enter ‘RDS’ and the title of the PhD project that you are applying for. You should ensure that you clearly indicate that you are applying for a funded studentship and the title of the topic or project on the proposal that you will need to upload when applying. If you would like to apply for more than one project, you will need to complete a further application form and specify the relevant title for each application to a topic or project.

If you do not clearly indicate that your application is for a funded studentship and state the title of the project applied for on the proposal, it may not be possible to consider your application for the appropriate funding.

For academic enquiries, please contact [email protected].

For administrative enquiries before or when making your application, contact [email protected]. 

After an application has been made, please contact [email protected].

The online application portal and all document templates required for an application can be accessed at:

https://www.tees.ac.uk/sections/research/students_prospective_c.cfm

Selection process

All applications received by the closing date will be considered. Successful applicants at the application stage will be shortlisted and contacted to arrange an interview. All interviews will be held online. Unsuccessful applicants will be contacted to confirm that the application will not be progressed. After interview, all interviewed applicants will be contacted to inform them of the outcome. Successful applicants will progress to an offer of a place, to commence in December 2024.

Research at Teesside

As a Teesside University research student, you will join a growing and dynamic research community, allowing you to share your experiences, insight and inspiration with fellow researchers. You will benefit from our academic expertise and be supported through a strong programme of research training. You will be offered opportunities and support at each stage of your research degree. Our research is designed to have impact, and to influence policy and practice within our region, the UK and beyond. We work with external organisations to anticipate and respond to research needs, and to put our research into practice in sectors as diverse as the arts, engineering, healthcare and computing. PhD students are encouraged to work with their supervisors to explore the potential impact of their work.

The successful candidate will be expected to participate fully in research group and centre activities, including training sessions and workshops, and will become a member of the University’s wider postgraduate research community. Mentoring and support will be provided for the development of a strong academic and professional CV during the PhD.

Key dates

• Closing date for applications is 5pm on 29 September 2024.
• Interviews will take place from 8 – 11 October 2024.
• Successful applicants will start on 2 December 2024