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(MCRC Non Clinical) Determining the role of chemokines in radiotherapy induced bowel inflammation

Project Description

Radiotherapy is delivered to 50-60% of all cancer patients and is a part of successful anti-cancer therapy in 40% of those cured of their disease. However early and late radiation-induced toxicity limits radiotherapy doses and results in long-term side effects. Radiotherapy is known to result in acute and chronic inflammation in the intestine, however the immune regulatory pathways involved are poorly understood. The late consequences of radiation-induced inflammation can be severe leading to bowel disturbance and bowel stricture which can substantially decrease the quality of life of cancer survivors. The development of these late gut side effects are poorly understood, however it appears that leukocyte recruitment is central to pathophysiology. The underlying biological mechanisms that mediate leukocyte recruitment and inflammation in radiotherapy induced gut inflammation toxicity therefore require further investigation.

Reactive Oxygen Species (ROS) and chemokines are key drivers of immune effector cell recruitment and appear critical to the acute and chronic inflammatory processes that subsequently lead to late radiation induced toxicity. In order for immune cells to leave the circulation and enter tissues, they must pass through the luminal glycocalyx barrier. This barrier is a sugar-rich meshwork that sits on top of endothelial cells, and controls vascular permeability and chemokine presentation. This project will explore the effect of radiotherapy on chemokine production, glycocalyx barrier permeability and how radiotherapy potentially alters the structure of the glycocalyx. These new insights will provide an enhanced understanding of how RT can modulate inflammatory cell recruitment to tissues. Finally, we will investigate whether we can therapeutically prevent this radiation induced inflammation. Recently the small molecule inhibitor of OGG1 has been shown to be a potent inhibitor of reactive oxygen species (ROS)-driven inflammation. We will therefore investigate the ability of OGG1 to interfere and reverse this ROS and chemokine driven radiation induced bowel inflammation.

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.

On the online application form select PhD Cancer Sciences. Applicants can only apply for up to TWO projects. This project has a start date of September 2020. Interviews are currently scheduled for Tuesday 25 February 2020.

Funding Notes

This Project is funded through the Cancer Research UK RadNet Manchester. This four year Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £19,000 per annum).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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