The role of the Laminin 332-Actin-Cholesterol axis in skin conditions with altered lipid profiles

皮肤的表皮屏障在保护身体免受过多的水分流失、环境化学物质和微生物感染方面起着至关重要的作用。皮肤屏障可以被损伤、潜在的遗传条件、炎症、环境变化和年龄所破坏，导致皮肤干燥、容易受损。对干性皮肤的研究发现角质细胞积累增加，皮肤脂质组成及其总丰度也发生了变化。研究罕见的遗传性皮肤病，我们已经确定了基膜蛋白层粘连蛋白332和皮肤脂质之间的联系。我们相信，同样的机制也会导致干性皮肤和其他相关皮肤/头皮状况的皮肤脂质损失。这个BBSRC联合利华CTP博士研究生的目的是研究皮肤干燥的机制，并确定治疗皮肤干燥的新策略。我们将利用现有的皮肤样本、分离的“干皮肤”角质形成细胞和层粘连蛋白敲除细胞系来研究层粘连蛋白332表达对皮肤屏障形成和皮肤脂质的影响。学生将有机会获得细胞和分子生物学技术、3D皮肤模型、成像（包括活细胞和共聚焦成像）、SFC-MS/MS脂质分析和电子显微镜方面的经验。

The skin's epidermal barrier plays a vital role in protecting the body from excessive water loss, environmental chemicals and microbial infection. The skin barrier can be disrupted by injury, underlying genetic conditions, inflammation, environmental changes and by age leading to dry, easily-damaged skin. Investigations of dry skin have identified increased corneocyte accumulation as well as alterations in both the composition of skin lipids and their total abundance. Studying rare inherited skin diseases we have identified a link between the basement membrane protein laminin 332 and skin lipids. We believe the same mechanism is responsible for the loss of skin lipids in dry skin and other related skin/scalp conditions.The aim of this BBSRC Unilever CTP PhD studentship is to investigate the mechanism underlying dry skin and identify new strategies for the treatment of dry skin. We will utilise existing skin samples, isolated 'dry skin' keratinocytes and laminin knockdown cell lines to investigate the effect of laminin 332 expression on skin barrier formation and skin lipids. The student will have the opportunity to gain experience in cell and molecular biology techniques, 3D skin models, imaging (including live cell and confocal imaging), SFC-MS/MS lipid analysis and Electron-microscopy.