Breast cancer (BC) remains the second leading cause of cancer death for UK women. Around 90% of breast cancer cases are sporadic, but there are no obvious carcinogens or driver mutations, unlike other cancers. This raises questions about the source of genomic damage required to initiate BC, particularly in women at higher risk of breast cancer. The second largest risk factor for BC is high mammographic density (MD), the amount of radiopaque tissue seen in a mammogram. High MD areas are where the collagenous extracellular matrix (ECM) that supports the epithelial ducts is mechanically stiffer. ECM stiffness can change cell phenotype, altering gene expression and promoting oncogenic changes. Our recent work has shown that the increased tissue stiffness associated with high MD alters gene expression in mammary epithelial cells, leading to increased genomic damage and transformation.
Analysis of the gene expression in stiffer ECM highlights that many of the changes are in fundamental metabolic pathways. Cancer cells have altered metabolism, and several recent studies have shown that ECM stiffness can reprogram metabolism in many cell types. We now want to ask are these metabolic changes indicative of BC risk, and whether they directly lead to the genomic damage driving cancer initiation. To do this we will establish metabolite profiling using state of the art mass spectrometry and cell culture models that mimic tissue stiffness in breast. We will look for the same metabolic fingerprints seen in the culture model in breast tissue from high-risk women. We will determine if these metabolic changes link ECM stiffness and genomic damage by using approaches such as gene expression and CRIPSR/Cas9 gene knock out in the culture models. This will help us understand how changes in cellular metabolism might drive BC initiation, identify biomarkers for early BC detection and highlight novel targets for prevention.
Entry Requirements
Candidates must hold, or be about to obtain, a minimum upper second class undergraduate degree, or the equivalent qualifications gained outside the UK, in a relevant subject. A related master's degree would be an advantage.
How to Apply
To be considered for this project you MUST submit a formal online application form. Details of how to apply are available here (https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/apply/). For Visa requirements, international candidates must select the full-time study option.
This is a targeted studentship in the area of cancer which will include partial funding from a donor. Full details can be found here https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
General enquiries can be directed to [Email Address Removed].
Interviews: Week commencing 10 January 2022
Commencement: October 2022
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/
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