Development of a bioink to enable bioprinting of stromal tissue mimics

About the Project

Human tissues are complex architectures made up of a combination of cells spatially organised within distinct matrices. Cells make and maintain this matrix, through which they receive biochemical, mechanical, and topological stimuli that are crucial to establish and maintain tissue function. This relationship is central to our understanding of a diverse range of biological processes, from development to ageing, and in diseases such as fibrosis and cancer. However, cell-matrix relationships are poorly defined to date due to a lack of defined model systems that can precisely mimic 3D cellular microenvironments.

We are particularly interested in the study of breast cancer, the second highest cause of mortality in women. After ageing, the highest risk predictor for breast cancer is high mammographic density (MD) - the opacity of breast tissue observed in a mammogram. Little is known about why high MD correlates with risk, although our work suggests that it is in part due to a fault in mechanical signalling. Our understanding of cancer has been improved by the use of 3D-matrix model systems based on Matrigel, a complex mixture of proteins derived from tumours grown in mice. However, Matrigel is difficult to work with: its composition is highly variable, and its mechanical properties are unreflective of physiology.

To successfully model human breast tissue, we require: (i) a synthetic basement membrane (BM) matrix that can support the growth of epithelial cells and (ii) a synthetic stromal matrix to support the growth of fibroblast cells. The synthetic matrices should incorporate appropriate cell adhesion ligands, possess excellent mechanical integrity, facilitate control over topological features such as porosity, and be printable to enable spatial patterning through interfacing distinct cell-matrix compartments. In this project, the student will develop a Matrigel alternative using biocompatible polymers that incorporate functional matrix-specific proteins through recombinant engineering and peptide synthesis strategies.

Eligibility

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a subject related to the proposal, but including: biomedical sciences, cell biology, cancer biology, molecular biology, biochemistry, polymer chemistry, or biophysics.

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

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cell Matrix Research Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

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: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

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