Analysis of Class-I Histone Deacetylase Function in Embryonic Development, Tissue Formation and Homeostasis.

胚胎发育、组织形成和稳态中 I 类组蛋白脱乙酰酶功能的分析。

• 批准号: G0600135/1
• 负责人: Shaun Cowley
• 金额: $ 125.46万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600135%2F1
• 关键词: Analysis; Class; Histone; Deacetylase; Function

‘Histone deacetylase‘ (HDAC) enzymes are present in all cells of the body. Their function is to switch genes ‘off‘, and making sure they stay ‘off‘. In many respects shutting a gene down is every bit as important as switching a gene on. I intend to study how three different HDAC enzymes (HDACs 1, 2 and 8) do this. One of the best methods for understanding how an enzyme works is to generate mutant cells in which the specific enzyme has been inactivated. These ‘knock-out‘ cells can then be examined for changes in their characteristics, lack of growth for instance, which can then be attributed to the function of that particular enzyme. If we use mouse stem cells to this then we can create HDAC knock-out mice.HDAC enzymes represent an exciting medical opportunity because they are ‘druggable‘. Already, inhibitors of HDAC activity are being tested in the clinic as anti-cancer agents, and in the laboratory for their beneficial affects on an Alzheimer‘s disease and their anti-inflammatory properties. There is therefore a compelling applied, as well as academic, motivation for studying their physiological roles in order to assess their potential as pharmacological targets for use in treating patients.

人体所有细胞中都存在“组蛋白脱乙酰基酶”（HDAC）酶。他们的功能是“关闭”基因，并确保它们保持“离开”。在许多方面，关闭基因的关闭与打开基因一样重要。我打算研究三种不同的HDAC酶（HDAC 1、2和8）如何做到这一点。理解酶的工作原理的最佳方法之一是产生突变细胞，其中特定酶被灭活。然后可以检查这些“敲除”细胞的特征变化，例如缺乏生长，然后可以归因于该特定酶的功能。如果我们对此使用小鼠干细胞，那么我们可以创建HDAC敲除小鼠。HDAC酶代表了令人兴奋的医疗机会，因为它们是“可药物的”。已经准备好，HDAC活性的抑制剂正在临床中作为抗癌药物进行测试，以及在实验室中对其对阿尔茨海默氏病和他们的抗议物质的有益影响的实验室中的抑制作用。因此，有一种引人注目的应用以及学术的动机，以研究其身体角色，以评估其作为治疗患者使用的药物目标的潜力。