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Developing new 3D-hydrogel models of the human mammary gland to investigate breast cancer initiation


   Department of Materials

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  Prof Alberto Saiani, Prof Aline Miller  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Breast cancer remains the second highest cause of cancer deaths in the UK, with it killing more women than pancreatic, oesophageal and brain cancer combined. The main drivers for breast cancer occurrence remain unclear. After age, one of the major risk factors is mammography density which is an established biomarker of breast cancer risk. This has raised the possibility that increased cancer risk is in part due to altered mechano-signalling in mammary epithelial cells.

 Mechano-signalling is a well-established concept in cell biology. Cells not only respond to soluble signals, such as growth factors and cytokines, but also to the mechanical properties of their microenvironment. In breast cancer it has been shown that the increased stiffness of the extracellular matrix associated with a tumour drives changes in cancer cell behaviour, stimulating a more invasive phenotype. We hypothesise that changes in mechano-signalling associated with increased mammography density may also promote changes in normal mammary epithelial cells behaviour, promoting the oncogenic phenotype and acquisition of mutations.

 A significant limitation of current animal/bio derived hydrogel models (e.g: matrigel/alginate) is their composition which varies significantly between batches, and affects the reproducibility of cultures. Secondly, the high content of contaminant and signals masks any changes in the proteins secreted by the cells preventing proteomic analysis. Thus, the field has reached the limit in terms of what can be done with these current composite gels. There is therefore a need to develop novel fully defined synthetic hydrogel models.

 This project will develop fully defined peptide-based hydrogel models to mimic 3D-breast tissue in order to understand the changes associated with increased breast cancer risk.

 For the purpose of this project, we will exploit the work performed by our group over the past decade in the design of peptide-based hydrogels for biomedical application and the broad interdisciplinary expertise of the supervisory team to design novel models of breast cancer initiation. The project will focus on understanding the interaction between mammary epithelial cells and peptide hydrogel and design novel functional system that allow the development of cellular structure (breast acini) mimicking breast tissue and investigate the triggers for cancer development mainly focusing on mechano-signalling.

 Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact. We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

 We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder). 

Academic background of candidates

Master in related field: Biomaterials, Biomedical Engineering, Biological Sciences

To apply please follow the link below:

https://www.manchester.ac.uk/study/postgraduate-research/admissions/how-to-apply/


Funding Notes

This project is available to UK Students only.
Standard UKRI fees and stipend (£16,062)
Start date: January 2023
Closing date: 30th September 2022
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