How does ageing related loss of basement membrane collagen regulate epidermal barrier homeostasis

衰老相关的基底膜胶原蛋白损失如何调节表皮屏障稳态

• 批准号: 2620155
• 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: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2620155
• 关键词: How; does; ageing; related; loss

Skin ageing is a universal problem. The basement membrane separates the keratinocytes (which are cells containing keratin) in the skin from the connective tissue layer. During ageing, skin thinning is associated with decreased basement membrane collagens (BMC) and an impaired skin barrier. The skin barrier is important in protecting the skin from external insults such as infection. We have found a link between loss of BMC and changes to the cytoskeleton of the keratinocyte and the nucleus which contains deoxyribonucleic acid (DNA). Aims and Objectives:In the first objective, the student will engineer keratinocytes to have loss of BMC collagen. We can then study how loss of BMC collagen affects processes like cell division and how the cells form skin in vitro in 3D cultures. We can also characterize the skin barrier. In the 2nd objective, the student will stress the 3D cultures generated in objective 1 using mechanical stretch or ultraviolet radiation, to see how this affects the shape of the nucleus and the nuclear internal structures and processes such as metabolic responses to stress. In the 3rd objective, a technique will be used to look at interactions between proteins and DNA in the nucleus to try and identify genes that might be regulating skin barrier development that are altered by loss of BMC. Findings will be confirmed in young and ageing skin to show that our results are relevant to ageing. Finally, at Unilever the student will use computational tools to identify compounds that might be used to reverse the effects of loss of BMC on the skin barrier and normal skin homeostasis. These compounds can then be used on ageing skin models in the laboratory. Potential applications and benefits:This work should give insights into normal skin ageing and how it could be improved. This is relevant to not just how humans look as they get older, but also to prevention of skin infection and better wound healing. It could result in development of new creams to reverse skin ageing or maintain a youthful appearance.

皮肤老化是一个普遍的问题。地下膜将角质形成细胞（其中是含有角蛋白的细胞）与结缔组织层分开。在衰老过程中，皮肤变薄与地下室膜胶原蛋白（BMC）和皮肤屏障受损有关。皮肤屏障对于保护皮肤免受外部侮辱（例如感染）很重要。我们发现BMC丧失与角质形成细胞的细胞骨架与含有脱氧核糖核酸（DNA）的细胞核之间有联系。目的和目标：在第一个目标中，学生将设计角质形成细胞损失BMC胶原蛋白。然后，我们可以研究BMC胶原蛋白的损失如何影响细胞分裂等过程，以及细胞在3D培养物中如何在体外形成皮肤。我们还可以表征皮肤障碍。在第二个目标中，学生将使用机械拉伸或紫外线辐射在目标1中产生的3D培养物强调这如何影响核的形状以及核内部结构和过程，例如对压力的代谢反应。在第三个目标中，将使用一种技术来研究核中蛋白质与DNA之间的相互作用，以尝试鉴定可能正在调节因损失BMC改变皮肤屏障发育的基因。在年轻和衰老的皮肤中，将确认发现我们的结果与衰老有关。最后，在联合利华，学生将使用计算工具来识别可能用于扭转BMC损失对皮肤屏障和正常皮肤稳态的影响的化合物。然后，这些化合物可以用于实验室的衰老皮肤模型。潜在的应用和好处：这项工作应洞悉正常皮肤老化以及如何改善。这不仅与人类变老一样，而且与预防皮肤感染和更好的伤口愈合有关。这可能会导致新面霜的发展以逆转皮肤衰老或保持年轻的外观。