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

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‘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.