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

“组蛋白脱乙酰酶”（HDAC）酶存在于身体的所有细胞中。它们的功能是“关闭”基因，并确保它们保持“关闭”状态。在许多方面，关闭一个基因和打开一个基因一样重要。我打算研究三种不同的HDAC酶（HDAC1，2和8）是如何做到这一点的。了解酶如何工作的最好方法之一是产生突变细胞，其中特定的酶已经失活。然后可以检查这些“敲除”细胞的特征变化，例如缺乏生长，然后可以将其归因于该特定酶的功能。如果我们使用小鼠干细胞，那么我们就可以制造出HDAC基因敲除小鼠。HDAC酶代表了一个令人兴奋的医学机会，因为它们是“可药用的”。HDAC活性抑制剂已经在临床上作为抗癌药物进行了测试，并在实验室中对阿尔茨海默病及其抗炎特性的有益影响进行了测试。因此，有一个令人信服的应用，以及学术，动机，研究他们的生理作用，以评估其作为药理学目标，用于治疗患者的潜力。

‘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.