Spring/Summer 2020 RadNet PhD Studentships2020-03-30T14:20:14+00:00

Spring/Summer 2020 RadNet PhD Studentships

3x 4-Year PhD Studentships with CRUK City of London Centre

Cancer Research UK (CRUK) have awarded funding to the Cancer Research UK City of London (CoL) Centre to create a CRUK Radiation Research Unit – RadNet. The unit will feature an ambitious research programme for radiation oncology and radiation biology. This network will accelerate the development of advanced radiotherapy techniques, challenging the boundaries of this mainstay treatment through world-first exploratory projects.

Four year CRUK-funded, non-clinical PhD fellowships to start in Spring/Summer 2020 are available in the following research themes:

1. The mechanisms of radiation resistance, including cancer evolution and cancer stem cells.
2. Radiation combinations: How the tumour microenvironment and immune system affect the response to radiotherapy.
3. Targeting and technology: Advanced radiotherapy techniques, such as proton beam therapy and stereotactic radiotherapy, which uses multiple beams of radiation that converge on the tumour for children and young people’s cancers.
4. Outcomes and risk predictions: Personalising radiotherapy using artificial intelligence, computational models and improved tumour imaging.

Projects will be based across the City of London Centre’s  partners (UCL, King’s, Barts or the Crick) and will include multi-disciplinary training and exposure to physical sciences.

Via the Department of Medical Physics & Biomedical Engineering at UCL, CRUK CoL is inviting applications for 3 x 4-year studentships, with 3 x 2 month research placements across the Centre. These PhD studentships are an ideal opportunity for outstanding applicants with a scientific background who would like to carry out research projects in radiation biology, cancer and radiotherapy.

Projects available

Supervisors: Professor Simona Parrinello, UCL Cancer Institute (primary supervisor) and Dr Simon Boulton, the Francis Crick Institute (secondary supervisor).

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.

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.

Supervisors: Professor John Anderson, UCL GOS Institute of Child Health (primary supervisor), Professor Tony Ng, KCL Comprehensive Cancer Centre (secondary supervisor) and Dr Jane Sosabowski, QMUL Barts Cancer Institute (secondary supervisor).

In this PhD doctoral study, we will use preclinical disease models such as patient derived tumour organoids (PDOs) and syngeneic tumour models, to address how radiotherapy may impact on the ability of T cells (including anti-GD2 chimeric antigen receptor (CAR) T cells) to penetrate into the core of the tumour. We postulate that treatment resistance or disease recurrence following radiotherapy may be due to the inability of the immune cells to penetrate into the core of the tumour even though radiotherapy has ‘sensitised’ immune recognition.

Besides the main laboratory (Anderson lab) that provides training and knowledge on pediatric oncology and immunotherapy, the successful candidate will learn to use multiphoton optical imaging to visualise the cancer:immune interaction in 3D (Ng, KCL/UCL) as well as whole body imaging (Sosabowski, QMUL).

More detailed information about the research project is available on request from Professor John Anderson at j.anderson@ucl.ac.uk.

Person Specification

Suitable candidates must have a minimum upper second-class Honours degree in an associated discipline, or an overseas qualification of an equivalent standard. They must also have knowledge of molecular biology, immunology and imaging. Experience of laboratory techniques such as tissue culture, FACS, confocal microscopy and in vivo experience would also be desirable.

Supervisors: Professor Maria Hawkins, UCL Dept. of Medical Physics and Biomedical Engineering (primary supervisor) and Dr Ivana Bjedov, UCL Cancer Institute (secondary supervisor).

Technical advances in radiotherapy, including proton therapy, now permit highly targeted radiation to be delivered to tumour with significant normal tissue sparing. Radiation dose escalation has been postulated to improve intrathoracic malignancies, however clinical trials of dose escalation have been negative with a worse outcome in the dose escalation arm due to normal tissue toxicity (lung and heart). Furthermore, combining novel agents such as immunotherapy and targeted agents (ATR, ATM and other inhibitors) is challenging due to increased normal tissue toxicity.

Pathways implicated in normal tissue radiation injury are poorly understood. Senescence in normal-tissue stem cells, with accelerated ageing as a consequence of cancer treatment is an example of a potential pathway. Cellular senescence, which is a normal consequence of ageing, can result from DNA damage, oxidative stress, and chronic inflammation. Proton radiation appears to produce more cancer cell death through senescence when compared to X-rays.

Laboratory studies have confirmed the importance of senescence as a cause of radiation toxicity in irradiated lungs. Other work has suggested that the factors elaborated by senescent cells may contribute to tumour progression as senescent stem cells are unable to replenish themselves and injured cells; they may also contribute to disease through the secretion of proinflammatory factors. Preventing or clearing senescent cells has recently been shown to reduce the toxicity of radiation and to mitigate ageing-related illnesses in animal models.

Our initial findings show that rapamycin – an approved compound for immunosuppression and advanced kidney carcinoma, when used in very small doses has a radioprotective effect for normal tissue which would have potential utility to reduce toxicities in radiotherapy treated cancers. One of the postulated mechanisms could be senescence prevention. The role of the immune system in normal toxicity prevention is not known.

More detailed information about the research project is available on request from Professor Maria Hawkins at m.hawkins@ucl.ac.uk.

Person Specification

Suitable candidates must have a minimum upper second-class Honours degree in an associated discipline, or an overseas qualification of an equivalent standard. They must also have knowledge of molecular biology, immunology and imaging. Experience of laboratory techniques such as tissue culture, FACS, confocal microscopy and in vivo experience would also be desirable.

For all studentships essential criteria include 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.

Further information

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. In addition to carrying out their PhD research and participating in core mandatory activities, including taking part in multi-disciplinary radiation research workshops and seminars and participating in CoL cohort-building 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. 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.

Funding will be for 4 years,  and will include 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.

How to apply

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 cruk-radnet-cityoflondon@ucl.ac.uk. Please write ‘Application for PhD Studentship [number, Title]’ in the subject line of the email.