Unveiling the structural architecture of skin layers through cryo-electron microscopy

Description du projet

Dans les profondeurs de l’architecture de la peau

Notre peau est composée de trois couches, chacune dotées de fonctions distinctes. La couche externe de l’épiderme comporte également plusieurs couches représentant différents stades de différenciation des kératinocytes et son intégrité repose sur l’interaction de ces cellules avec la matrice lipidique. Financé par le programme Actions Marie Skłodowska-Curie, le projet cryoDerm se propose d’étudier l’organisation de l’épiderme. Les chercheurs feront appel à la cryo-microscopie électronique avancée et se concentreront sur le rôle des microfilaments de kératine dans la résilience et la résistance de la peau ainsi que dans la formation des lipides. Ces travaux fourniront une image haute résolution de l’architecture de la peau, essentielle à la compréhension de son homéostasie et de sa santé.

Objectif

The skin is the largest organ of the human body. It has a variety of functions and it is organized in three different layers, the epidermis, dermis and hypodermis, all three of which have a different anatomy and function. The epidermis itself is also composed of several layers divided from the inside to the outside and these layers illustrate the various stages of keratinocyte differentiation, which is the process by which the basal layer proliferates and produces new cells that will differentiate towards the skin’s surface. Skin integrity is maintained by the relationship between keratinocytes and the specialized matrix of lipids they are embedded in. This project will use state-of-the-art cryo-focused ion beam scanning electron microscopy lift-out milling and cryo-electron tomography of natively preserved skin tissue to obtain insights into the ultrastructural organization of the epidermis. More specifically we aim to describe and quantify how the keratin microfilaments network is arranged throughout the skin layers and contributes to skin resilience and strength, and in what way this organization is correlated to the lipid formation and delivery. Our initial results reveal new insights into the architecture of the outermost skin layers, specifically their intermediate filaments organization and lipid layer organization to provide strength and separation between different cell layers, respectively. ISTA is the ideal research institute for this project, due to the abundant access to high-end electron microscopes necessary for this project achievement. The outcome of this will be a high resolution in situ structure architecture that will allow a better understanding of skin homeostasis. Results will be disseminated through key research conferences and high-impact open-access publications. Communication activities will be achieved through 3D rendered visual scientific illustrations targeting social media platforms and institute-organized public outreach events.