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The aim of the project is to determine the response of quiescent GSCs to radiotherapy and investigate the molecular mechanisms that underpin their radioresistance, focusing on DNA repair pathways.
- Primary supervisor: Prof Simona Parrinello (UCL)
- Secondary supervisor: Dr Simon Boulton (Crick)
Candidates will need to qualify as UK/EU fee payers.
Closing date: Tuesday 14 April 2020
Project description
Non-clinical 4-year PhD project: Understanding the role of cancer stem cell quiescence in glioblastoma radio-resistance
Glioblastoma (GBM) is the most common and malignant primary brain tumour. Despite aggressive treatment, which includes surgical resection, chemo and radiotherapy, GBM invariably recurs leading to a median survival of less than 15 months. Recurrence is largely driven by a subpopulation of therapy-resistant tumour cells with stem cell properties, termed glioma stem cells (GSC). Increasing evidence suggests that, similar to their normal counterparts, GSC are slow cycling or quiescent. It is well established that quiescence shields GSC from chemotherapeutic agents that target cycling cells. In contrast, its role in radioresistance is much less clear.
Using novel mouse models of GBM that incorporate quiescence reporters, the successful candidate will determine the response of quiescent GSCs to radiotherapy and investigate the molecular mechanisms that underpin their radioresistance, focusing on DNA repair pathways. During the project the student will develop skills in a wide range of in vivo and molecular biology techniques, including intravital 2-photon microscopy, histology, FACS, tissue culture, single cell RNA-sequencing, and gene editing. Understanding the molecular basis of GSC radioresistance will ultimately guide the development of improved therapeutic strategies for this devastating disease. CoL Centre RadNet students will follow the CRUK CoL Centre PhD training programme. In addition to carrying out their PhD research and participating in core mandatory activities, each trainee will have a ‘customised’ training programme, which will be developed with their supervisors taking into account the trainee’s background and PhD project needs. Mandatory training activities will include an induction programme to introduce trainees to doing a PhD, the Centre and its science, its infrastructure cores, experiment design, research integrity, and science project management.
In addition, RadNet students will take part in multi-disciplinary radiation research workshops and seminars and participate in CoL cohort-building activities, including giving talks (as part of an annual Centre trainee meetings and Centre symposia), attending meetings, networking events, and seminars. The ‘customised’ elements of the programme will include short research placements, and training in a vast range of scientific and transferable skills, accessible via the Centre partners and beyond. There will also be a strong emphasis on career mentoring and support. PhD students will follow the four-year CRUK CoL Centre PhD training programme and will be based in their primary supervisor’s research group. Students will register for their PhD at the primary supervisor’s university. All students will have a three-person thesis committee made up of Centre faculty that they will meet with regularly to discuss progress and receive guidance and advice.
More detailed information about the research project is available on request from Professor Simona Parrinello at s.parrinello@ucl.ac.uk.
- Person specification
Suitable candidates must have a minimum upper second-class Honours degree in molecular/cell biology, biochemistry or a closely related field, or an overseas qualification of an equivalent standard. They must also have knowledge of life sciences, as required for this project. Experience in applying computational techniques to data analysis and having molecular and cell biological techniques such as PCR, western blotting, cloning, fluorescence microscopy, flow cytometry, tissue processing and immunohistochemistry, would also be desirable. Other essential criteria includes having potential to develop expertise in new areas of the subject; ability to develop understanding of complex problems and apply in-depth knowledge to address them; has potential for innovation and initiative, the ability to work both independently and as part of a team; and appropriate English language skills.
Funding and application
Funding will be for 4 years, with a tax free stipend of £21,000 per year plus UK/EU-level university fees. Due to funding body restrictions, only UK / EU nationals are eligible to apply for this programme.
The closing date is 14th April 2020 and the anticipated start date is spring/summer 2020.
To apply for this studentship, you must submit only two documents:
1. Your full CV including a short summary (<500 words) detailing how your experience and ability matches the project and the person specification.
2. A single PDF file containing scans of two academic references, and the transcripts of your university degree(s) showing your unit/module marks.
These two documents should then be emailed to Michelle Craft, RadNet City of London project manager, at m.tu@ucl.ac.uk.
Please write ‘Application for PhD glioblastoma radioresistance’ in the subject line of the email.
