(MCRC Non-Clinical RadNet) Radiation-induced vascular inflammation following brain radiotherapy – understanding mechanisms of injury and impact on cognitive decline

Cancers of the brain and head and neck are often treated with external beam radiotherapy either prior to or following surgery. Despite significant advances in radiotherapy planning techniques, substantial volumes of normal brain tissue are inevitably irradiated alongside tumour, damaging blood vessels and brain tissue. Clinical reports suggest that between 50% and 90% of patients that survive beyond 6 months of treatment develop neurocognitive deficits related to radiation exposure which severely degrade quality of life.

In healthy brain tissue, the blood-brain barrier (BBB) regulates delivery of nutrients to brain cells, and plays a vital role protecting brain tissue from damaging toxins and microbes present in the bloodstream. It is well known that ionising radiation disrupts the BBB, a process that alters neurovascular coupling and promotes immune-cell infiltration. This project will aim to determine whether blood-brain barrier injury (i.e. vascular inflammation) contributes to long-term deterioration of cognition following radiotherapy, and to determine the timing and mechanisms involved. To do this, the student will use a clinically relevant rodent model of radiotherapy-induced vascular injury combined with state-of-the art in-vivo longitudinal MRI and ex-vivo tissue and blood analyses (i.e. 3D immunohistochemistry, ELISA, flow-cytometry).

This project is highly multidisciplinary, cutting across themes of radiotherapy, immuno-oncology, imaging biomarkers, and molecular pathology. The ideal student will have or be expected to obtain a first class in a biological or medical sciences degree. Prior research experience (e.g. Master’s project) in the field of neuro-inflammation or immuno-oncology is desirable. The successful student will gain training in advanced MRI techniques, in-vivo skills, brain and vascular immunology, and radiation oncology, and will join our highly multidisciplinary team of scientists and PhD students working on immuno-oncology and neuroimaging research in Manchester.

 Entry Requirements

Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. 

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the CRUK Manchester Centre PhD Training Scheme (MCRC) website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

General enquiries can be directed to [Email Address Removed].

Equality, diversity and inclusion is fundamental to the success of The University of Manchester and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

The CRUK RadNet Manchester Unit was one of only three major units awarded. It builds on the 10-year history of an external collaborating “One Manchester” approach to cancer team science in radiotherapy-related research (RRR). This has been achieved by our multi-disciplinary expertise in biology, clinical oncology, physics, software development, engineering and imaging. Manchester is recognised nationally as a Clinical and Translational Radiotherapy Research Working Group (CTRad) Centre of Excellence in Radiotherapy Research and the only centre in the UK with strength across all disciplines (biology, clinical, physics, technology).

The CRUK RadNet Manchester Unit Vision statement is: “As an integrated world-leading translational radiation oncology programme, we address the challenges of diverse patient characteristics to achieve individualised physical and biological targeting based on real-time outcomes and a deep mechanistic understanding of immune response, comorbidity and genomics.” This Vision aligns with CRUK’s research strategy through Collaborative Hubs and new science.

Interview date – WB 4 April 2022