DISSECTING THE FUNCTION OF INDIVIDUAL NF-kappaB SUBUNITS IN INFLAMMATION

剖析单个 NF-kappaB 亚基在炎症中的功能

• 批准号: G0501087/1
• 负责人: Irina Udalova
• 金额: $ 41.16万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501087%2F1
• 关键词: DISSECTING; FUNCTION; INDIVIDUAL; NF; kappaB

Inflammation is a normal physiological response to infection and injury, but can lead to extensive tissue damage and disability when elicited in excess. Pathological consequences of sustained inflammatory response include variety of autoimmune diseases, such as rheumatoid arthritis, Crohn?s disease, ankylosing spondylitis and multiple sclerosis. A sustained inflammatory response is often linked to the break down in regulation of production of inflammatory molecules. In a normal self-resolving body response to infection or injury inflammatory molecules are produced for a defined period of time, while in chronic autoimmune conditions their production is prolonged. The production of many inflammatory molecules is controlled by a key family of regulatory proteins called NF-kappaB. All five NF-kappaB proteins are present at the site of inflammation and are active, but at different times. Why there are five similar but not identical NF-kappaB proteins, why they come to and leave the site of inflammation at different times and how they control the level and the length of production of inflammatory molecules is a subject of this investigation. Understanding how each NF-kappaB protein functions and what molecules it regulates is important for the development of a new generation of therapeutic approaches. These would only target specific cellular events without interfering with the global host defence mechanisms. It will also help scientists to better understand why we have so many families of ostensibly similar proteins and what specific functions they hold.The research will be carried out by Dr Irina Udalova at the Kennedy Institute of Rheumatology, Imperial College, and will be laboratory based using novel genomic techniques and computational methods. The proposed novel techniques will replace the use of animals in research. Results generated in this study will be communicated through peer-reviewed scientific journals and through annual reports from the Kennedy Institute and presented at scientific meetings.

炎症是对感染和损伤的正常生理反应，但当炎症过度时，可导致广泛的组织损伤和残疾。持续炎症反应的病理后果包括各种自身免疫性疾病，如类风湿关节炎、克罗恩？S疾病，强直性脊柱炎和多发性硬化症。持续的炎症反应通常与炎症分子产生调节的中断有关。在正常的身体对感染或损伤的自我解决反应中，炎症分子在一段确定的时间内产生，而在慢性自身免疫性疾病中，它们的产生是延长的。许多炎症分子的产生是由一个叫做NF-kappaB的关键调节蛋白家族控制的。所有五种NF-kappaB蛋白都存在于炎症部位并活跃，但在不同的时间。为什么有五种相似但不相同的NF-kappaB蛋白，为什么它们在不同的时间到达和离开炎症部位，以及它们如何控制炎症分子产生的水平和长度是本研究的主题。了解每个NF-kappaB蛋白的功能及其调节的分子对新一代治疗方法的发展至关重要。这些只会针对特定的细胞事件，而不会干扰宿主的整体防御机制。它还将帮助科学家更好地理解为什么我们有这么多表面上相似的蛋白质家族，以及它们所具有的特定功能。这项研究将由帝国理工学院肯尼迪风湿病研究所的Irina Udalova博士进行，并将使用新的基因组技术和计算方法在实验室进行。提出的新技术将取代动物在研究中的使用。本研究的结果将通过同行评议的科学期刊和肯尼迪研究所的年度报告进行交流，并在科学会议上发表。