Genomic Profiling of Pheochromocytoma and Paraganglioma (PPGL) to Resolve Missing Driver Mutations

Details of the Project

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumours characterised by substantial clinical variability and a complex genetic basis. Although major advances have been made in identifying inherited and somatic driver mutations, including alterations in NF1, VHL, RET, HRAS, and ATRX, a significant subset of PPGL cases still lack identifiable drivers, creating a persistent “driver deficit.” Understanding these unresolved genetic events is essential for improving diagnosis, risk stratification, and treatment, particularly for patients with metastatic disease.

Previous work conducted by our group has included short-read whole-genome sequencing (WGS) of PPGL and genome-wide DNA methylation profiling using Illumina EPIC arrays. Although these analyses identified several candidate structural variants and epigenetic alterations, many rearrangements could not be resolved due to the limitations of short-read sequencing, especially in repetitive or complex genomic regions.

This project will employ Oxford Nanopore long-read sequencing (LRS) on selected PPGL samples to overcome these limitations. Nanopore sequencing offers the ability to generate long contiguous reads, enabling accurate detection of intragenic variants, structural rearrangements, fusion events, and tumour-specific methylation signatures in a single assay.

The project aims to:

1. Identify previously undetectable PPGL driver mutations and structural variants.
2. Resolve complex rearrangements such as the previously observed but inconclusive fusion event.
3. Compare methylation patterns derived from LRS with existing EPIC array profiles to validate emerging long-read methylation methods.
4. Provide a robust dataset to support high-impact publications and future multimillion-pound funding applications focused on rare tumour genomics.

This project will significantly advance understanding of PPGL molecular pathogenesis and has strong translational potential for improving diagnostics and clinical management.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. As part of the application, you will be required to confirm that you will provide this additional funding. Please indicate this on the application form in the funding section.

Location

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

a] a First or Upper Second Class award in their Undergraduate Degree (Bachelors or UG Masters) from a UK institution, in a subject judged by Aston to be relevant to the proposed research.

OR

b] a Merit (or above)* in a Postgraduate Masters degree in a relevant subject AND an Undergraduate Degree (Bachelors or UG Masters), both from UK institutions.

*where appropriate.

Qualifications from overseas institutions will be also considered but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Contact information

For formal enquiries about this project contact Dr Mohammed ‘Mo’ Elasrag at m.elasrag@aston.ac.uk

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected.Your application must include:

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience.
4. A Curriculum Vitae (Resume) which details your education and work history.
5. Two academic refereeswho can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.
6. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.
7. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.

Funding Notes

This project covers the Home tuition fees. Candidates who do not have Home status will be responsible for the difference in tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7.