Activation of the Inflammasome in Skin by Malassezia fungal species

马拉色菌激活皮肤炎症小体

• 批准号: 2159522
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2159522
• 关键词: Activation; Inflammasome; Skin; Malassezia; fungal

Studentship strategic priority area:Basic Bioscience Underpinning HeathKeywords: Inflammasome Dermatitis Innate ImmunityAbstract: Inflammation underlies many important skin conditions. Recent work has highlighted the importance of inflammation in driving the extremely common scalp condition of dandruff. Although inflammation can act initially to help repair damaged skin, a persistent inflammatory response can perpetuate damage, leading to increased epithelial turnover and decreased epithelial permeability barrier function that characterises the abnormal skin function in dandruff. Triggers to this inflammatory response are not clear, but much evidence shows the importance of the fungal skin commensal of the genus Malassezia in initiating and perpetuating this condition. One mechanism by which Malassezia could produce an inflammatory response in skin is through activation of the inflammasome. The inflammasome is a multisubunit protein platform that leads to processing and activation of the cytokine interleukin-1beta (IL-1beta). IL-1beta is detected in increased amounts in dandruff sufferers and thus may play an important role in the development of this condition. We hypothesise that activation of the inflammasome by Malassezia spp. is an important factor in initiating and propagating inflammatory responses in dandruff. We have the following aims:1. To define the ability of Malassezia globosa and restricta to activate the inflammasome in human keratinocytes.2. To determine the composition of the inflammasome activated by these fungi.3. To explore the interactions of sebum lipids and fungal metabolites on inflammasome activation.The student will receive training in the following:. Tissue culture of primary macrophages and other cells derived for wild type and select knockout mice. Western blotting, and immunological methods . CRISPR/Cas9 gene editing . Single cell flow cytometry . Cryoelectron microscopy for ultrastructural analysis of the inflammasome. Systems biology approaches to understand the factors that tip the cell to activate the inflammasome.

学生战略优先领域：基础生物科学支撑健康关键词：炎性皮炎先天免疫摘要：炎症是许多重要皮肤状况的基础。最近的研究强调了炎症在导致头皮屑这种极其常见的头皮状况中的重要性。虽然炎症最初可以帮助修复受损的皮肤，但持续的炎症反应可以使损伤永久化，导致上皮更新增加和上皮通透性屏障功能降低，这是头皮屑皮肤功能异常的特征。这种炎症反应的触发因素尚不清楚，但许多证据表明马拉色菌属的皮肤共生真菌在引发和维持这种情况方面的重要性。马拉色菌在皮肤中产生炎症反应的一种机制是通过激活炎症小体。炎症小体是一个多亚基蛋白平台，可导致细胞因子白细胞介素-1β (IL-1β) 的加工和激活。在头皮屑患者中检测到的 IL-1β 含量增加，因此可能在这种情况的发展中发挥重要作用。我们假设马拉色菌激活炎症小体。是引发和传播头皮屑炎症反应的重要因素。我们的目标如下： 1．明确球形马拉色菌和限制性马拉色菌激活人角质形成细胞炎症小体的能力。 2．确定这些真菌激活的炎症小体的组成。 3．探索皮脂脂质和真菌代谢物对炎症小体激活的相互作用。学生将接受以下培训：原代巨噬细胞和源自野生型和选择敲除小鼠的其他细胞的组织培养。蛋白质印迹和免疫学方法。 CRISPR/Cas9 基因编辑。单细胞流式细胞仪。用于炎性体超微结构分析的冷冻电镜。系统生物学方法来了解促使细胞激活炎症小体的因素。