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Investigating the interplay between the immune consequences of pelvic radiotherapy, the gut microbiome and long-term side-effects


   Faculty of Biology, Medicine and Health


About the Project

The North West has a higher prevalence of pelvic cancers compared to the rest of England. Around 40% of all people with cancer have curative-intent radiotherapy (RT) with 1 in 3 people having pelvic radiotherapy as an important component of their anti-cancer treatment. Bowel toxicity in the form of colitis, causing diarrhoea, pain and weight loss, is a common side-effect of abdominal/ pelvic RT, resulting in considerable morbidity. For people living with and beyond cancer, long term side-effects can be life-changing with 30-50% of people experiencing bowel toxicity despite advances in technology to deliver increasingly targeted radiotherapy.

Linking with our clinical partners in Preston, the candidate will use our established experimental translational immunology expertise to investigate the underlying mechanisms of radiation-induced immune changes. In this study the student will build on these preclinical findings and investigate the radiation induced immunological changes in the bowel mucosa and microbiota to enhance our understanding of acute and late bowel toxicity. The aims of the project will be determine the utility of a rectal lavage technique to investigate acute and late changes to the bowel mucosa and blood borne biomarkers of toxicity including key components of the gut endothelial glycocalyx and investigate how pelvic radiotherapy influences the gut microbiome and its potential role in bowel toxicity. The results of this study will enable the development of novel techniques and biomarkers in the assessment of mechanism of radiotherapy-induced toxicity and will directly inform the development of clinical studies of dietary and therapeutic intervention, building an integrated clinical service to support people with cancer across the North West.

Eligibility 

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.  Candidates with experience in immuno-oncology are encouraged to apply.

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How to Apply 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.  

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team   

Equality, Diversity and Inclusion  

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/ 


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website View Website

References

Price JM, Mistry HB, Betts G, Cheadle EJ, Dixon L, Garcez K, Illidge T, Iyizoba-Ebozue Z, Lee LW, McPartlin A, Prestwich RJD, Papageorgiou S, Pritchard DJ, Sykes A, West CM, Thomson DJ. Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer. J Clin Oncol. 2022 Jul 10;40(20):2203-2212. doi: 10.1200/JCO.21.01991. Epub 2022 Apr 6.
Cytlak, U.M., Dyer, D.P., Honeychurch, J., Williams, K.J., Travis, M.A., Illidge, T.M. Immunomodulation by radiotherapy in tumour control and normal tissue toxicity. Nat Rev Immunol 22, 124–138 (2022). https://doi.org/10.1038/s41577-021-00568-1.
Choudhury A, Porta N, Hall E, Song YP, Owen R, MacKay R, West CML, Lewis R, Hussain SA, James ND, Huddart R, Hoskin P. BC2001 and BCON investigators. Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol. 2021 Feb;22(2):246-255.
Joseph N, Cicchetti A, McWilliam A, Webb A, Seibold P, Fiorino C, Cozzarini C, Veldeman L, Bultijnck R, Fonteyne V, Talbot CJ, Symonds PR, Johnson K, Rattay T, Lambrecht M, Haustermans K, De Meerleer G, Elliott RM, Sperk E, Herskind C, Veldwijk M, Avuzzi B, Giandini T, Valdagni R, Azria D, Jacquet MF, Charissoux M, Vega A, Aguado-Barrera ME, Gómez-Caamaño A, Franco P, Garibaldi E, Girelli G, Iotti C, Vavassori V, Chang-Claude J, West CML, Rancati T, Choudhury A. High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer. Front Oncol. 2022 Oct 26;12:937934. doi: 10.3389/fonc.2022.937934.
Massi MC, Gasperoni F, Ieva F, Paganoni AM, Zunino P, Manzoni A, Franco NR, Veldeman L, Ost P, Fonteyne V, Talbot CJ, Rattay T, Webb A, Symonds PR, Johnson K, Lambrecht M, Haustermans K, De Meerleer G, de Ruysscher D, Vanneste B, Van Limbergen E, Choudhury A, Elliott RM, Sperk E, Herskind C, Veldwijk MR, Avuzzi B, Giandini T, Valdagni R, Cicchetti A, Azria D, Jacquet MF, Rosenstein BS, Stock RG, Collado K, Vega A, Aguado-Barrera ME, Calvo P, Dunning AM, Fachal L, Kerns SL, Payne D, Chang-Claude J, Seibold P, West CML, Rancati T. A Deep Learning Approach Validates Genetic Risk Factors for Late Toxicity After Prostate Cancer Radiotherapy in a REQUITE Multi-National Cohort. Front Oncol. 2020 Oct 15;10:541281.

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