(A*STAR) Elucidating the role of polyamines in the epidermal skin barrier

Delayed wound healing is a major health issue affecting one in 50 people. The process of wound healing is a highly orchestrated process involving many cell types and regulatory networks. Crucially, the outermost cell layer of the skin, the keratinocytes must migrate and proliferate in order to help seal the wound. Chronic non-healing wounds are characterized by a failure of the wound edge keratinocytes to migrate, preventing the wound from healing. Keratinocyte migration can be affected by extrinsic factors such as commensal or pathogenic microbes on the skin as well as intrinsic factors such as polyamine metabolites.

This project addresses the role of a group of metabolites called polyamines in the regulation of barrier formation and the epidermal inflammatory response in wound healing and pigmentation. The polyamines putrescine, spermidine and spermine are essential cations that are present in all cells and are essential for cellular function. The two major regulators AMD1 and ODC1 control the levels and ratios of the polyamines. Changes in polyamine levels, through interaction with DNA and RNA, can influence gene expression and drive cellular behavioural changes. The polyamines are present at high levels in the epidermis and are up-regulated during wounding and inflammation. In addition, they have been shown to have strong anti-bacterial properties. It is currently unknown what the role of the polyamines in these contexts are though. Furthermore, the impact of commensal and pathogenic bacteria on polyamine function is not well understood. This project aims to determine how regulated changes in polyamine levels influence the inflammatory process to enable wounding healing and to prevent infection. The project will use combination of human cell culture and tissue analysis combined with genome wide RNA sequencing studies to interrogate the interplay between the polyamine pathway, the inflammatory response and keratinocyte behaviour in the epidermis. Students on the project will develop expertise in immunology, the microbiome and epidermal biology. These studies are aimed at understanding the regulatory controls governing normal epidermal cells with the aim of better understanding clinical epidermal condition.

Entry Requirements:
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.