Modelling rare genetic disease variants in Neurodevelopmental Disorders: strengthening Xenopus as a key screening tool for diagnosis and improved mechanistic understanding.

Applications are invited for a fully-funded three year PhD to commence in October 2024. 

The PhD will be based in the Faculty of Science and Health and will be supervised by Dr Annie Godwin, Dr Helen Willsey (UCSF) and Professor Matt Guille. 

Candidates applying for this project may be eligible to compete for one of a small number of bursaries available. Successful applicants will receive a bursary to cover tuition fees for three years and a stipend in line with the UKRI rate (£19,237 for 2024/25). Bursary recipients will also receive a £1,500 p.a. for project costs/consumables.

Costs for student visa and immigration health surcharge are not covered by this bursary. For further guidance and advice visit our international and EU students ‘Visa FAQs’ page.    

Improvements in DNA sequencing and analysis, coupled with advances in engineering biology have greatly enhanced the prospects for molecular diagnoses of the 1 in 17 UK residents with rare genetic diseases. Nonetheless, this has created a new diagnosis bottleneck for around half of patients when there is no established link between the suspect gene variant and disease it may cause. Neurodevelopmental disorders (NDD) are particularly difficult to diagnose due to the heterogeneity of patient phenotypes and the limited studies to understand the evolutionary conservation of NDD phenotypic presentation across vertebrate model organisms. A further barrier to improving patient welfare is that many genetic variants of uncertain significance (VUS) are now being discovered in poorly characterised genes or non-coding regions of the genome. This lack of knowledge often results in the clinicians caring for those patients learning little from the molecular diagnosis about the natural history and progression of the disease, or the potential to mitigate symptoms safely.

This PhD programme is to discover how to combine bioinformatics, engineering biology, phenotyping and therapeutic agents in the functional model Xenopus tropicalis, to define a process to enhance understanding around ultra-rare NDD presentation. We aim to demonstrate to healthcare providers the power of the frog model and develop a clear route to diagnosis for patients with VUS that cause NDDs. It is important because over three-quarters of the patients arising from genome sequencing projects have undiagnosable NDDs. The programme will be achieved through collaboration with the European Xenopus Resource Centre’s (EXRC) XenMD programme, and three major UK-based clinical genetics centres to prioritise gene variants for testing based on bioinformatics, clinical input and the outputs of the functional modelling.

How to apply

Please note that email applications are not accepted. If you have any project-specific questions please contact Dr Annie Godwin (annie.godwin@port.ac.uk), quoting the project code.

When you are ready to apply, you can use our online application form. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV.  Our ‘How to Apply’ page offers further guidance on the PhD application process. 

If you want to be considered for this funded PhD opportunity you must quote project code ELS50230125 when applying.