Beyond Coding Variants: Gene Regulatory Causes of Unresolved Polycystic Kidney Disease Revealed by Integrated Multi-Omic Profiling

Prof John Sayer
Dr Juliana Estefania Arcila Galvis,
Dr Sarra Ryan
Prof H Cordell

Wednesday, May 20, 2026
Competition Funded PhD Project (UK Students Only)

About the Project

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder and a leading cause of kidney failure worldwide. Accurate genetic diagnosis informs prognosis, enables family (cascade) testing, and is increasingly required for access to emerging gene-targeted therapies. While most cases are explained by protein-altering variants in genes such as PKD1, PKD2, and IFT140, up to 10% of clinically diagnosed patients remain genetically unresolved even after whole-genome sequencing, excluding them from precision medicine pathways.

This PhD offers an exciting opportunity to uncover a hidden layer of genetic disease. ADPKD genes are dosage-sensitive: even subtle reductions in gene expression can drive cyst formation. We hypothesise that many unresolved cases are caused by non-coding regulatory variants affecting promoters, enhancers, splicing elements, or chromatin architecture. These classes of variation often missed by standard diagnostic genetic data pipelines.

The student will work at the cutting edge of genomic medicine, integrating whole-genome sequencing, RNA sequencing, and deep phenotyping within the National Genomic Research Library. They will develop new long read sequencing approaches to potentially identify new variants in poorly explored regions of the genome. Kidney-specific regulatory annotation will be informed by epigenomic resources from the International Human Epigenome Consortium (IHEC), providing a unique opportunity to combine multi-omic data with disease biology.

Training will span computational and experimental genomics. You will develop skills in rare variant prioritisation, statistical genetics, and machine learning, leveraging large population datasets including UK Biobank, All of Us, and Our Future Health to strengthen pathogenic inference. High-confidence variants will then be functionally tested in patient-derived human urine renal epithelial cells using expression and splicing assays, gaining hands-on experience in cellular modelling and molecular validation.

By the end of the PhD, you will have developed a reproducible framework for detecting regulatory disease mechanisms in ADPKD, delivering diagnoses for previously unresolved families and establishing an approach transferable across rare kidney disorders. The work will culminate in high-impact publications and clinically relevant reporting aligned with FAIR data principles.

Based at Newcastle University in a multidisciplinary renal genetics laboratory, this project offers outstanding interdisciplinary training at the interface of genomics, computational biology, and translational nephrology. It is ideally suited to an ambitious student motivated to bridge discovery science and patient benefit in the era of precision medicine.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.

HOW TO APPLY

Please complete the following application form – Google Form

Applicants can only apply for 1 project; any additional applications will not be accepted.

Applicants should send the following documents to FMSstudentships@newcastle.ac.uk:

• a CV (including contact details of at least two academic (or other relevant) referees).
• a Cover letter – stating your project choice, as well as including additional information you feel is pertinent to your application.
• copies of your relevant undergraduate degree transcripts and certificates.
• a copy of your IELTS or TOEFL English language certificate (where required)
• a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE

Please submit your documents in the following format only:

• each document should be submitted as a separate attachment and should be named as follows: candidate surname, candidate name – document type. For example: Jones, Jamie – CV; Jones, Jamie – cover letter.
• Please submit .pdf documents where possible for your CV, cover letter, transcripts and certificates. Do not submit photos of certificates.
• Do not combine documents into one pdf. You may zip separate documents into a zip file to send via email if required.
• When emailing your application, please use the email subject header: FMS PhD Application 2026

Applications not meeting these criteria may be rejected.

Informal enquiries may be made to the lead supervisor of the project you are interested in.

The deadline for all applications is 12 noon BST (UK time) on Wednesday 20^th May 2026.