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Understanding and minimizing radiation damage in breast tissues


Project Description

Human beings are subjected to many forms of radiation both natural (principally ultraviolet radiation [UVR]) and artificial (diagnostic and therapeutic X-rays). The clinical implications of this exposure can be debilitating and potentially life-threatening. For example, non-ionizing UVR may induce acute inflammation and pain and, in the longer term, chronic photo-ageing and skin cancer. Ionizing X-ray radiation is used therapeutically (as radiotherapy) to treat cancer but in the breast, damage to surrounding tissues can be severely debilitating.

Whilst the interactions of ionizing and non-ionizing radiation with cells and with chromosomal DNA are relatively well-characterised the impact of radiation on the surrounding extracellular matrix is poorly understood. It is clear however that not only is cell behaviour profoundly influenced by the composition structure and mechanical proteins of this matrix but that radiation exposure can damage ECM proteins ether direct, by the production of reactive oxygen species or by the upregulation of proteases. By bringing together expertise in photobiology, skin ageing, X-ray imaging, biomaterials and breast cancer this PhD project will use human skin and breast tissue samples and state of the art 3D cell culture models to characterise the impact of exposure to environmentally attainable doses of UVR and therapeutically administered doses of X-ray radiation on ECM structure (newly developed analytical mass spectrometry approaches), cell behaviour (RNASeq analysis) and tissue/construct mechanical properties (atomic force microscopy). The information generated by this PhD will play a vital role in defining the key mechanistic pathways which lead to skin ageing and cancer and in modifying breast radiotherapy regimens by, for example, synchronising with circadian rhythms to reduce unwanted side-effects. The student will have the opportunity to work with world-leading experts in internationally recognised institutions such as the Christie Hospital, the Welcome Trust centre of Cell-Matrix research and the Diamond Light Source Synchrotron in Oxford.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject including biology, medicine, biochemistry, cell biology, physics and martials science. Candidates with experience in radiation biology and photobiology are encouraged to apply.

Training/techniques to be provided:
Tissue acquisition (including ethics)) and processing.
Cell culture - including advanced 3D culture models.
X-ray and UVR radiation and calibration.
Characterisation of model systems by advanced imaging (micro-computed X-ray tomography, confocal microscopy) and by proteomics (mass spectrometry) and transcriptomics (RNASeq).

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. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

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.

References

Hibbert SA, Watson REB, Griffiths CEM, Gibbs NK, Sherratt MJ. 2019. Selective proteolysis by matrix metalloproteinases of photo-oxidised dermal extracellular matrix proteins. Cellular Signalling 54:191-199.

Lopez-Guimet, J, Pena-Perez, L, Bradley, RS, Garcia-Canadilla, P, Disney, C, Geng, H, Bodey, AJ, Withers, PJ, Bijnens, B, Sherratt, MJ, Egea, G. 2018. MicroCT imaging reveals differential 3D micro-scale remodelling of the murine aorta in ageing and Marfan syndrome. Theranostics 8:6038-6052.

Madi K, Staines KA, Bay BK, Javaheri B, Geng, H, Bodey AJ, Cartmell S, Pitsillides AA, Lee PD “In situ characterisation of nano-scale strains in a physiologically-representative whole joint loading model” Nature Biomedical Engineering 2019 in press

Is breast seroma after tumour resection associated with patient-reported breast appearance change following radiotherapy? Results from the IMPORT HIGH (CRUK/06/003) trial. Bhattacharya IS, Haviland JS, Perotti C, Eaton D, Gulliford S, Harris E, Coles CE, Kirwan CC, Bliss JM, Kirby AM; IMPORT Trialists. Radiother Oncol. 2019 Jul;136:190-196.

CC Kirwan. On behalf of the PRIMETIME Trials Management Group. It’s PRIMETIME. Post-operative avoidance of radiotherapy: biomarker selection of women at very low risk of local recurrence. Clin Oncol (R Coll Radiol). 2016 Sep;28(9):594-6.

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