The outer protective layer of our skin, the epidermis, is comprised of differentiated keratinocytes. The molecular regulation of epidermal differentiation is still poorly understood although it is important for many pathological conditions. We have examined the hypothesis that cyclophilin D induced mitochondrial permeability transition pore opening is a critical determinant of epidermal differentiation by performing in vivo experiments on knockout mice as well as in vitro studies on cultured keratinocytes. Ablation or downregulation of cyclophilin D led to reduced differentiation denoted by lower number of epidermal skin layers and reduced expression of early differentiating genes. All these findings indicate that cyclophilin D mediated mPTP opening is critical for epidermal differentiation. To further establish this mechanism, we will perform experiments based on gene knockdown techniques, cell culture, qPCR, pharmacological treatments and confocal microscopy. The project is expected to be submitted for publication within a year. We are searching for a highly motivated master student that can be a part of this project for a longer period of time. It is an excellent opportunity to learn important lab methods in a well funded lab and get published. If successfull, the master student rotation may turn into a PhD-studentship.