Integrative strategies for improved therapy of KBTBD4-dependent high-risk childhood brain tumours

About the Project

Medulloblastoma is the most common malignant brain tumour affecting children, accounting for 10% of all childhood cancer deaths. Among its disease groups, Group 3 medulloblastoma is the most aggressive and remains extremely challenging to treat. Approximately 20% of these tumours carry amplification of the oncogene MYC, which is strongly associated with poor survival. Although MYC itself cannot be directly targeted with small molecules, our research group has developed an advanced screening pipeline to identify promising MYC‑targeting small molecule combinations, which are now progressing through pre‑clinical translation.

A newly emerging driver of Group 3 disease is mutation of KBTBD4, an E3‑ubiquitin ligase adaptor found in approximately 6% of Group 3 cases. These mutations are thought to promote tumour development through abnormal protein degradation, but their molecular and clinical effects remain largely unexplored. Interestingly, KBTBD4-mutation and MYC-amplification do not co-occur, raising the exciting possibility that they may converge on similar oncogenic programmes. Like MYC, KBTBD4 is also considered "non‑druggable", and as such is ideally suited to the integrative multi‑omic and functional pipelines established in our group.

This PhD project offers an opportunity to investigate a novel driver event in childhood brain cancer. The successful applicant will use cutting‑edge experimental systems including patient-derived and 3D cellular models, high‑throughput drug screening, network-based disease modelling and transcriptomic and proteomic patient datasets to elucidate the tumour biology underpinning mutant-KBTBD4, identify actionable KBTBD4-dependent vulnerabilities and assess their interplay with MYC-driven disease. Together, the data generated will identify therapeutic targets for high-risk Group 3 medulloblastoma and work-up associated small molecules for clinical translation.

You will join the Paediatric Brain Tumour Group (PBTG) – a multidisciplinary research team with an established track record in medulloblastoma target discovery, translation and training the next-generation of translational researchers. Training will cover molecular and cellular biology techniques, multi‑omic analysis, molecular pathology, drug screening, and advanced disease modelling.

This project is ideally suited to motivated students with an interest in cancer biology, molecular pathology, precision medicine, and translational research.

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.