Establishing and maintaining regulatory competency in the human genome.

随着年龄的增长，我们会失去修复受损组织和器官的能力。其中一个原因是由于一组被称为干细胞的特殊细胞的丧失。这些细胞具有修复受损细胞的能力，并有可能改变其身份以产生多种不同的细胞类型。这一特性促使研究人员尝试将这些细胞用于再生医学，在实验室制造细胞，以取代我们身体中受损的细胞。然而，要进行这一过程，重要的是要了解干细胞如何转变为其他类型的细胞。这个问题的部分答案是，他们的控制系统的连接方式和DNA的包装方式发生了变化。这个项目将研究被称为FOXK2-SIN3A蛋白质复合体的分子开关是如何促进这一重新连接过程的。我们将在人类胚胎干细胞中进行研究，并检查当这些细胞改变命运创造不同类型细胞时发生的分子事件。我们的发现将帮助我们了解干细胞如何改变其身份，并可能为我们提供机械信息，使我们能够改进这一过程以获得治疗益处，并了解与年龄相关的疾病是如何发展的。

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.