Our Community Blog Using skin models to study skin barrier function January 2020 About me: I am a second year PhD student at the University of Dundee working under the supervision of Professor Sara Brown and Professor Angus Lamond. Prior to starting my PhD, I completed a BSc (Hons) in Cell Biology from the University of St. Andrews and a MRes in Cancer Biology from the University of Dundee. I have an interest in learning about how our genetics contribute to the development of human disease. Having personally suffered with atopic eczema (AE) as a child and knowing friends and family with severe atopic eczema I can relate to the negative impact it can have on an individual’s quality of life. Therefore, I have a personal interest in learning more and contributing research findings about the mechanisms behind AE development and progression so that in the future more effective treatments can be provided. Using skin models to study skin barrier function The skin barrier Skin acts as an essential barrier in maintaining human health in everyday life. When describing the skin barrier, we refer to a number of barrier elements from the physical barrier to chemical, photo-protective, immunological, diffusion and microbiological barriers. These barriers work collectively by protecting against the loss of water and nutrients from within to the external environment whilst simultaneously preventing the penetration of infectious agents and external factors. When one or more of these elements of the skin barrier becomes disrupted it can lead to the increased susceptibility towards the development of skin diseases, such as atopic eczema (AE, aka atopic dermatitis or simply eczema). Studying skin barrier and atopic eczema using a 3D skin model AE is a very common itchy and inflammatory skin disease. The high occurrence of AE has been attributed in part due to two main factors: the environment and our genetics. Both of which play a role in the inflammatory response observed in AE. In the Brown group we are interested in answering the question what genetic mechanisms in skin barrier function may be important in AE development and progression? To study this we use a three-dimensional skin model. This model is composed of primary human fibroblasts (component of the dermis, or lower layer of the skin) and keratinocytes (main components of the epidermis, or outer layer of the skin). Once the skin model is developed, which takes approximately 12 days, we can use functional tests to measure how healthy the skin barrier is. In addition, we use more advanced techniques to look more closely at why these changes are occurring. This research will help to provide new information into the role candidate genes play in skin barrier function. Because this reduction in skin barrier health is considered a prerequisite to AE, we can then use this information to answer the question whether the genes studied are likely important in AE development and/or progression. This will allow us to further our understanding into the cause and development of AE and to discover novel targets for future treatment development. Extending a thanks to BSF and its supporters Throughout my PhD project I aim to use the above approach to study candidate genes from genetic studies of AE to assess their potential novel roles in skin barrier function and AE development and progression. The research I am conducting during my PhD Studentship has been made possible thanks to the support from the British Skin Foundation. For this I would like to extend a thank you to the British Skin Foundation and its supporters. Figure 1. Construction of a three-dimensional skin model to assess skin barrier function. On day 1 cultured human fibroblasts are embedded in a fibrin gel matrix forming the dermal equivalent. On day two cultured human keratinocytes are reverse transfected with siRNA to enable reduction in the expression of our gene of interest. The keratinocytes are added on top of the dermal equivalent to form the epidermal equivalent. On day 5 the developing skin model is lifted onto a grid exposing the epidermis to the air allowing for further cell differentiation and epidermal formation. On day 12 the skin model is fully formed and functional, molecular and observational tests can be carried out to assess the health and function of the skin barrier. Kimberley Morrison Help us fund more research like this More on atopic eczema By donating to skin disease research you are helping us to find treatments and cures for common conditions like eczema, acne and psoriasis through to potential killers like melanoma skin cancer. Thank you.