Signaling in the crypt: a novel metabolic pathway in intestinal stem cells

隐窝信号传导：肠道干细胞的一种新代谢途径

• 批准号: DP210103065
• 负责人: A/Prof Robyn Meech
• 金额: $ 33.2万
• 依托单位: Flinders University
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2022
• 资助国家: 澳大利亚
• 起止时间: 2022-02-01 至 2025-01-30
• 项目状态: 未结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP210103065
• 关键词: Signaling; crypt; novel; metabolic; pathway

The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.

肠道是身体中更新最快的组织，由高度活跃的干细胞生态位驱动。胆汁酸正在成为这种干细胞生态位的关键调节剂，胆汁酸体内平衡的破坏对肠道更新和肠道健康产生深远的不利影响。 我们正在解决一个关键的差距，在我们的理解如何胆汁酸是控制在干细胞生态位。该项目的目的是确定一种名为UGT 8的新型酶在控制肠道干细胞对胆汁酸的反应中的关键作用;这是通过调节肠道干细胞模型中的UGT 8活性并确定对干细胞功能的影响以及控制肠道稳态和更新的关键信号通路来实现的。