Understanding the pathology of cardiac complications in a rare neurodevelopmental disease

About the Project

Do you think ribosomes, the ancient and evolutionary conserved RNA-protein factories that make all cellular proteins, are boring? That they are the same in all cells and that we know them inside-out?

If so - think again, because recent research in humans and model organisms revealed that “specialised” ribosomes with altered ribosomal RNA (rRNA) or protein (RP) components can modulate the cellular proteome due to a preference for the translation of certain mRNAs. Ribosome heterogeneity arises during differentiation and exists between different cell-types, but we don’t understand the mechanisms behind specialisation or its relevance in disease.

One key player in ribosome production is the RNA exosome, a ubiquitously-expressed multiprotein complex with ribonuclease activity. It is essential for ribosome assembly/function via its various roles in the processing/turnover of the rRNA and many other non-coding (nc)RNAs (Figure 1, https://rb.gy/oks7zv). These include small nucleolar (sno)RNAs that guide rRNA modifications (2’*-O-*Methyl, pseudouridine) and small nuclear (sn)RNAs essential for RP pre-mRNA splicing. Changes in these, often tissue-enriched, ncRNAs affect rRNA/RP modification or incorporation of different RP paralogues - contributing to ribosome heterogeneity.

Defects in the nine subunits (EXOSC1-9) of the core exosome should lead to fewer, altered or non-functional ribosomes in all cells. Yet, they surprisingly cause diseases with tissue-specific manifestations, such as neurodevelopmental and cardiac complications seen upon *EXOSC5* mutations (“CABAC”,https://www.omim.org/entry/619576). We have further shown that ribosome biogenesis defects caused by depletion of EXOSC5 and other EXOSC subunits trigger the nucleolar stress response (NSR) with downstream consequences like senescence, cell-cycle arrest and apoptosis (https://doi.org/10.26508/lsa.202000678).

This PhD project based at Newcastle, with a placement in Durham, will provide training in a unique breadth of approaches (biochemistry, cell biology, human cell culture, cryo-EM, RNA-seq) to test our hypothesis that exosome malfunction in ncRNA maturation/stability affects tissue-specific ribosome assembly/heterogeneity and alters the cell’s susceptibility to NSR. Specifically, we aim to determine how mutations in *EXOSC5* affect ribosomes in human cancer, neuroblastoma and cardiac cells, which will reveal mechanism(s) by which ribosomes are fine-tuned to make the right set of proteins for each cell-type.

This project is suited to students who need flexible working arrangements, and we welcome applications from minority backgrounds. A broad range of inter-disciplinary approaches established by the supervisory team (https://rb.gy/h9h6uq) will encourage innovative thinking and develop diverse technical expertise. Furthermore, the training will give the student a range of skills opening a wide choice of career options, within/outside of academia, post-PhD.

For informal enquiries please contactClaudia.Schneider@newcastle.ac.uk.

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 20th May 2026.