Understanding how secretory responses shape the downstream response of chondrocytes to inflammatory cytokine stimulation

了解分泌反应如何影响软骨细胞对炎症细胞因子刺激的下游反应

• 批准号: 2749889
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749889
• 关键词: Understanding; how; secretory; responses; shape

Healthy cartilage in our joints is essential for us to maintain an active life into old age. The cells that maintain cartilage are called chondrocytes and maintenance of their phenotype is important for healthy ageing. Inflammation is often a characteristic of an injured or diseased joint and excessive inflammatory stimulation has a negative effect on the integrity of the tissues within it. However, evidence suggests that some degree of inflammatory signalling is important for fundamental joint health although the mechanisms behind this have not been systematically investigated. This project will aim to map the consequences of inflammatory stimulation on chondrocyte function by examining how transient, physiologically relevant levels of inflammatory regulators called cytokines affect molecular signalling and downstream secretion of further inflammatory factors. Uniquely, it will utilise CRISPR/Cas9 gene editing technology to develop knockout cell lines that will allow us to tease apart the mechanisms affected in both the primary inflammatory stimulus and any secondary chondrocyte inflammatory responses. In addition, co-culture models using cells from different joint tissues will be employed to determine whether secondary, secretory responses to cytokine signalling can contribute to healthy cross talk between tissues within the joint. The student will be primarily placed at the University of Liverpool, in the group of Dr Simon Tew, who been studying molecular regulation of chondrocytes for many years. In addition, the project involves placement periods with Professor David Young at Newcastle University, whose laboratory has developed up a variety of functional gene editing and regulation models using Crispr/Cas9 technology

关节中的健康软骨对于我们在晚年保持积极的生活至关重要。维持软骨的细胞称为软骨细胞，维持其表型对于健康衰老非常重要。炎症通常是受伤或患病关节的一个特征，过度的炎症刺激会对关节内组织的完整性产生负面影响。然而，有证据表明，一定程度的炎症信号传导对于基本的关节健康很重要，尽管其背后的机制尚未得到系统研究。该项目旨在通过检查称为细胞因子的炎症调节剂的短暂、生理相关水平如何影响分子信号传导和进一步炎症因子的下游分泌，来绘制炎症刺激对软骨细胞功能的影响。独特的是，它将利用 CRISPR/Cas9 基因编辑技术来开发敲除细胞系，使我们能够梳理出原发性炎症刺激和任何继发性软骨细胞炎症反应中受影响的机制。此外，使用来自不同关节组织的细胞的共培养模型将用于确定对细胞因子信号传导的次级分泌反应是否有助于关节内组织之间的健康交流。该学生将主要被安置在利物浦大学的 Simon Tew 博士的团队中，他多年来一直在研究软骨细胞的分子调控。此外，该项目还包括在纽卡斯尔大学 David Young 教授的实习期间，该教授的实验室利用 Crispr/Cas9 技术开发了多种功能性基因编辑和调控模型