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

层粘连蛋白 332-肌动蛋白-胆固醇轴在脂质谱改变的皮肤状况中的作用

• 批准号: 2477252
• 金额: --
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2477252
• 关键词: role; Laminin; 332; Actin; Cholesterol

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.

皮肤的表皮屏障在保护身体免受过度失水、环境化学物质和微生物感染方面发挥着至关重要的作用。皮肤屏障可能会因损伤、潜在遗传条件、炎症、环境变化和年龄而受到破坏，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以及皮肤脂质成分及其总丰度的改变。通过研究罕见的遗传性皮肤病，我们发现了基底膜蛋白层粘连蛋白 332 与皮肤脂质之间的联系。我们相信相同的机制导致干性皮肤和其他相关皮肤/头皮状况中皮肤脂质的流失。联合利华 BBSRC CTP 博士生奖学金的目的是研究干性皮肤的潜在机制并确定治疗干性皮肤的新策略。我们将利用现有的皮肤样本、分离的“干性皮肤”角质形成细胞和层粘连蛋白敲低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。