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(MCRC Non-Clinical) Developing ex vivo models for breast cancer - understanding the link between tissue mechanics, genetic instability and cancer initiation

Project Description

Breast cancer is the most common form of cancer in women, with over 54,000 new cases each year in the UK, and over 11,500 of these women die. In order to reduce these numbers, the causes of breast cancer need to be understood, and why some women are at a higher risk of developing the disease in the first place. Mammographic breast density (MBD) is the amount of a woman’s breast tissue that appears radio opaque in a mammogram. Data over a number of decades has shown that women with significantly higher MBD are 4-6 times more likely to develop the disease than women with low MBD. After age, this represents the highest independent risk factor, but the biological basis for the increased risk is unknown. Recent studies have shown that regions of high MBD are where the connective extracellular matrix (ECM) supporting and surrounding the epithelial ducts contains collagen that is more cross-linked and mechanically stiffer. These findings suggest that altered tissue mechanics might contribute to increased breast cancer risk.

The mechanical properties of tissues are important determinants of cell function. Tissues have defined mechanical properties, which cells interpret, and changes in these properties are linked to disease. Preliminary data using mammary epithelial cell lines has shown that increased stiffness of their ECM induces changes in gene expression such that these cells are less like epithelia and acquire genomic instability leading to transformation. This project will study this mechanism in primary human cells, using 3D ex vivo models where we can examine how changes in the ECM mechanics alter cell behaviour that contribute to cancer initiation. This project will work within both the Manchester Cancer Research Centre and the Wellcome Trust Centre for Cell/Matrix Research to develop the ex vivo models.

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

Funding Notes

The 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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