Characterising and modulating the circadian biology of sebocytes to promote healthy skin barrier function

Human skin provides a critical barrier to protect us against environmental insults and help us prevent excessive water loss.

This barrier function is understood to be under rhythmic control between night and day and is maintained by a layer of lipids secreted on to the surface of the skin. The majority of these surface lipids originate from the sebocytes of the sebaceous gland.

In this project, we will build on our recent exciting discovery of a molecular circadian clock in human sebocytes, to understand the daily rhythms of sebaceous gland activity and how this rhythmic regulation contributes to healthy skin barrier function.

Our hypothesis is that the cell intrinsic circadian clocks in sebaceous glands temporally regulate genes and pathways for lipid synthesis and secretion.

The alignment of rhythmic sebaceous gland activity with daily environmental time cues is critical for the maintenance of skin barrier function.

During menopause, ageing or exposure to stressors, the sebocyte clocks become dysregulated, compromising the ability of skin to retain moisture and combat bacteria and pathogens. Specifically, we will address three inter-related questions: 1. Is there a daily rhythm in sebum excretion and composition in human skin? 2.

What are the rhythmic genes and pathways in human sebocytes and are these daily rhythms intrinsically regulated by sebocyte clocks? 3. How is the sebocyte clock regulated and can function be restored in aged or stressed skin?

Outcomes from this project will bring significant advances to our understanding of the daily dynamics of skin barrier function and will allow us to understand what goes wrong in shift workers, post-menopausal women, poor sleepers, ageing or under stress conditions.

These studies will ultimately enable us to design and evaluate the potential of novel chrono-actives which can reprogramme disrupted sebocyte clocks for better skin health.