Skin Regeneration: Mechanisms and Therapeutic Opportunities

About the Project

Healthy skin depends on strong adhesion between the cells of the upper layers of epidermis and the underlying dermis. When these attachment fails, as in trauma, chronic wounds or inherited blistering disorders, patients suffer from recurrent infections, impaired healing, and pain. The restoration process involves wound matrix, and epidermal adhesion to it, which doesn't happen in large-area wounds, resulting in ulcers or extensive scars.

MicroRNAs regulate skin adhesion by binding mRNAs, lowering expression of proteins. Our preliminary work identifies microRNA-29 (miR-29) as a key regulator of cell adhesion in healthy skin and reveals function of miR-29 in healing wounds. High levels of miR-29 weaken attachment of keratinocytes, while inhibition of miR-29 strengthens adhesion, enhances fibroblast matrix deposition, and prolongs keratinocyte growth. During wound repair, genetic deletion of miR-29 creates a pro-healing matrix with enhanced vascularization and faster formation of neo-epidermis – a new layer of the skin that ensures scar-free wound closure. We demonstrated that levels of miR-29 temporarily decreased in wounds, allowing enhanced pro-adhesive protein synthesis. In later phase of skin repair, miR-29 expression is restored to the upper layers of the skin and the dermis, ensuring suppression of pro-fibrotic proteins. This suggests that miR-29 acts as a molecular switch between regeneration and tissue failure, offering a promising therapeutic target.

In this project, you will:

1. Elucidate the mechanisms through which miR-29 represses adhesion of epithelial keratinocytes to the matrix. Determine how miR-29 regulates cell-matrix adhesion via integrin receptors by use of atomic force measurements (AFM), which will define the activation states of the receptors and how this is dependent on the presence of miR-29. 2. Determine how miR-29 regulates keratinocyte adhesion via the deposition of the matrix by dermal fibroblasts. You will culture human dermal fibroblasts transfected with miR-29 and will separate the deposited matrix to determine proteins upregulated as a result of miR-29 inhibition in an unbiased way using proteomics.

Eligibility

Applicants are expected to hold a minimum upper second-class undergraduate honours degree (or equivalent) in Biology. Research experience (e.g., Masters) in applying theoretical and practical methods to analyse and interpret the data generated by modern biology is desirable. Candidates with a minimum upper second-class undergraduate honours degree (or equivalent) in Biology/Biomedical Sciences will be also considered given the evidence of sufficient skills for the project.

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 Biology 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 2 (med) fee. Details of our different fee bands can be found on our website View Website