Clinical and single cell proteomics for rare disease diagnosis and characterisation

About the Project

The substantial burden of rare genetic disease (RD) in the UK affects ~3.5 million people, with 70 % of cases presenting in childhood. Of these, mitochondrial diseases are the most common. Difficulties arise in diagnosis of mitochondrial and other rare conditions when patients present with genetic variants of unknown significance (VUS); when the variant has no established disease-causing mechanism. Mitochondrial disease is further complicated as mitochondria possess their own multicopy genome (mtDNA). This gives rise to heteroplasmy; the presence of variable levels of wild-type and mutant mtDNA across different cells and tissues-lending additional, underexplored complexity to pathological mechanisms and phenotypic expression.

This PhD aims to enhance diagnosis of RD, and explore how heteroplasmic variability affects clinical expression of mitochondrial disease using cutting-edge proteomics and single-cell technologies at Newcastle University’s Faculty of Medical Sciences (FMS). You will join a thriving research environment spanning the Mitochondrial Research Group (MRG), with work underpinned by the latest generation of mass spectrometry technology. This technologically driven environment featuring applied- and discovery- science gives rise to one of the strongest rare disease research ecosystems in the UK, with exceptional access to clinical samples, expert collaborators, and state-of-the-art proteomics.

This project focuses on two major goals:

1. Improving proteomics-based diagnostic pipelines for mitochondrial and other rare diseases.
2. Using single-cell proteomics (SCP) and genomics to uncover the relationship between mtDNA heteroplasmy and the cellular proteome,and reveal new disease mechanisms.

You will develop advanced liquid chromatography–mass spectrometry (LC-MS) workflows, including SCP, to identify proteome-level signatures of disease, correlating these with mtDNA heteroplasmy. SCP is an emerging technology capable of quantifying thousands of proteins from individual cells, offering unprecedented insight into cellular diversity and mitochondrial dysfunction. By combining SCP with single-cell genomics, you will explore how mtDNA variation influences disease presentation and progression.

This project is ideal for applicants interested in proteomics, cell biology, rare disease mechanisms, or multi-omics innovation. You will gain hands-on experience in cell culture, sample preparation, LC-MS operation, proteomics method development, sample preparation-automation, and data analysis. As your skills develop, you will increasingly work with clinical samples, contributing directly to research with real diagnostic impact.

You will be supervised by experts in proteomics, mitochondrial genetics, and single-cell multiomics, ensuring strong scientific support while giving you the independence to develop as a researcher. This studentship provides an excellent platform for careers in academia, clinical science, biotechnology, or 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 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 20th May 2026.