A 3-year PhD Studentship funded by CCLG Little Princess Trust is available within the Childhood Brain Tumour Research Group in the Developmental Biology and Cancer Research and Teaching Department, Great Ormond Street UCL Institute of Child Health. The studentship will commence in April 2021 under the supervision of Dr Laura Donovan and Professor John Anderson.
Project overview
Medulloblastomas (MBs) are the most common cancerous brain tumours of children. Group3 MBs are the most aggressive type as they have the ability to spread through the brain and spinal cord. By time of diagnosis, group3 MBs have frequently metastasized, with overall survival depending heavily on the presence/absence of metastatic disease. Conventional treatment regimens include surgery, radiotherapy (in children 3≥) and high-dose chemotherapy, as a result many children are over-treated with non-specific therapies causing long-term developmental and neurological side-effects.
Chimeric antigen receptor T-cells (CARTs) are a branch of immunotherapy which involves reprogramming the patient’s own immune cells to fight a specific cancer. The lead supervisor’s research has shown CARTs are a successful therapy against cerebellar brain tumours. Immunotherapeutic strategies are now at the forefront of anti-cancer therapy, especially in leukaemia. However, with the majority of patients developing a resistance to the immunotherapy over time, enhancing sensitivity and persistence to these therapies is crucial to improve patient outcomes.
We have successfully identified a cell surface molecule found on the surface of MB primary tumours and tumour metastases. As a target for CART therapies, this cell surface protein has shown extraordinary results for the treatment of adult brain tumours. We hypothesise that CARTs against this protein can be leveraged as a safe and effective therapy against group3 MB. Using novel genetic modification techniques, we will re-engineer patient’s T-cells using next generation CARTs, reversing T-cell exhaustion, thereby enhancing persistence. Persistence of CART cell activity will be further increased by addition of a well-tolerated drug that both increases survival of T-cells whilst also being toxic to tumour cells. High-throughput biological and molecular characterisation of these combination strategies will be evaluated in tissue culture and in animal models using patient-derived group3 MB cells.
The project addresses the two major obstacles for MB treatment, the toxicity of current standard of care, and the lethality of the metastatic disease.
The project will utilise multiple techniques ranging from animal husbandry, three-dimensional co-culture modeling, flow cytometry, functional genomics and gene therapy strategies. The PhD student will work closely with world-wide collaborators, presenting their data at lab meetings, departmental meetings, and national and international conferences. The PhD student will also obtain generic skills by attending relevant courses run by UCL.
For further details, please see the project description on the ICH Website: “Enhancing CAR T-cell expansion and prolonged persistence for the effective treatment of paediatric medulloblastoma”
The student will receive a starting stipend of £17,400 per annum (including London weighting) as well as the cost of tuition fees based on UK fee status.
Personal Specification
Applicants should have, or expect to receive an upper second-class Bachelor’s degree and a Master’s degree (or equivalent work experience) in a relevant discipline or an overseas qualification of an equivalent standard.
Eligibilty
This studentship covers the cost of tuition fees based on the UK (Home) rate. Non-UK students can apply but will have to personally fund the difference between the UK (Home) rate and the overseas rate where they are not eligible for UK fee status.
NB: You will be asked about your likely fee status at the interview so we would advise you to contact the UCL Graduate Admissions Office for advice should you be unsure whether or not you meet the eligibility criteria for Home fee status. Further information on Brexit and the definitions for fee status assessment can be found on the UCL website and also the UKCISA website (Higher Education: Definitions for fee status assessment).
Application
To apply, please send a current CV including the contact details of two professional referees as well as a cover letter to [Email Address Removed]. Enquiries regarding the post can be made to Dr Laura Donovan ([Email Address Removed]).
Deadline for receipt of applications: Sunday 21st March 2021
Interview date: Tuesday 23rd March 2021