Funding

Funded (UK/EU students only)

Project code

ELS50230125

Department

School of the Environment and Life Sciences

Start dates

ELS50520825

Application deadline

20 August 2025

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 (UoP), Prof Matt Guille (UoP) and Prof Caroline Beck (Otago). The work will be conducted at the 兔子先生 within the European Xenopus Resource Centre (EXRC) which hosts the research programme Xenopus Modelling Disease (XenMD). The EXRC, alongside the National Xenopus Resource (NXR, Woods Hole, USA), is the leading international centre for Xenopus research globally. The project proposed here will align with ongoing work in the EXRC that uses engineering biology of the Xenopus genome to investigate the molecular basis of rare genetic diseases.

This project is subject to funding from the family-led patient advocacy organisation FAM177A1 Research Fund, and we would expect the successful candidate to work closely with the Fund, their scientific advisory board and Helen Hernandez (Perlara PBS, US). Should funding be offered, the successful applicant will receive a bursary to cover tuition fees for three years and a stipend in line with the UKRI rate. The recipient can also expect all project costs/consumables to be covered.

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 鈥榁isa FAQs鈥 page.    

 

The work on this project will involve:

  • Re-creating FAM177A1 patient gene variants in Xenopus tropicalis embryos and generating an epitope-tagged line to explore protein function using CRISPR-based gene editing techniques 
  • Pairing gain and loss of function with developmental assays in the early embryo, to improve mechanistic understanding of how FAM177A1 disease phenotypes arise
  • Employing existing XenMD phenotyping approaches, in the tadpole, to identify key cellular, molecular and organismal changes to discover disease mechanisms and identify markers for use in downstream therapeutic testing
  • Application of therapeutic agents, focusing on key hits from promising small molecule screens and in vivo gene therapy trials to assess changes in key disease-related phenotypes and markers

Improvements in DNA sequencing and analysis, coupled with advances in engineering biology have greatly enhanced the prospects for molecular diagnoses for patients with rare genetic diseases. A barrier to improving patient welfare is that many genetic variants are now being discovered in poorly characterised genes. 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 engineering biology, advances in phenotyping approaches and developmental screens in the functional model Xenopus tropicalis, to improve mechanistic understanding of FAM177A1-related Neurodevelopmental Disorder and test potential therapeutic hits. The programme will be achieved through collaboration between the European Xenopus Resource Centre鈥檚 (EXRC) Xenopus Modelling Disease (XenMD) research programme (兔子先生) and the FAM177A1 Research Fund.

 

To understand the changes that happen in FAM177A1-related Neurodevelopmental Disorder, we will re-create patient gene variants in tadpoles. The changes caused to the tadpoles will be analysed in detail, including their behaviour, morphology and neuronal function together with the cellular and molecular alterations that underpin these using 鈥渙mic鈥 analyses. These data will contribute to a collaboration through the FAM177A1 Research Fund鈥檚 Scientific Advisory Panel with other gene function analysis systems to enhance understanding of the disease mechanism. Finally, the lead compounds that have been shown to mitigate the effect of FAM177A1 variations in promising therapeutic screens will be tested in the tadpoles and their effect on the molecular alterations assessed in vivo. This will begin to provide a firm basis for moving between molecular diagnosis of patients and therapeutic intervention. 

 

References

doi: 10.1056/NEJMoa1714458, doi: 10.1038/gim.2015.30, doi: 10.1016/j.gim.2024.101166, doi: 10.1083/jcb.202311189, doi: 10.1186/s13073-021-00850-w, doi: 10.1016/j.ajhg.2022.05.009, doi: 10.1093/brain/awad380, doi: 10.1101/2023.10.11.23295963, doi: 10.1111/jnc.15836, doi: 10.1242/dmm.050754

 

Entry requirements

You should be a UK or EU citizen. You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) and ideally a Master鈥檚 degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications, it is encouraged that these applicants get in contact before applying. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

Candidates are expected to hold (or be about to obtain) a minimum 2.1 (or equivalent) in Biochemistry, Biology, Genetics, Neuroscience or a related discipline. A Master鈥檚 degree in a relevant subject area and/or experience in a related area/discipline is very desirable. 

Any candidates with an interest in rare genetic diseases, genomics, neuroscience or behavioural science are encouraged to apply.


 

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 . 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 鈥How to Apply鈥 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 ELS50520825 when applying.