Establishing and maintaining regulatory competency in the human genome.

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As we age, we lose the capacity to repair damaged tissues and organs. One reason for this is due to the loss of a specialised set of cells known as stem cells. These cells have the capability of restoring damaged cells and have the potential to change their identity to produce multiple different cell types. This property has led researchers to try to use these cells in regenerative medicine to make cells in the laboratory which can replace damaged cells in our body. However to undertake this process it is important to understand how stem cells can change into other cell types. Part of the answer to this, is a change in how their control systems are wired, and how their DNA is packaged up. This project will investigate how a molecular switch, known as the FOXK2-SIN3A protein complex, contributes to this rewiring process. We will conduct our studies in human embryonic stem cells and examine the molecular events that occur as these cells change fate to create different cell types. Our findings will help us understand how stem cells can change their identity, and potentially will provide us with mechanistic information that enables us to both improve this process for therapeutic benefit and to understand how age related diseases develop.