Establishing and maintaining regulatory competency in the human genome.

随着年龄的增长，我们失去了修复受损组织和器官的能力。其中一个原因是由于失去了一组专门的细胞，称为干细胞。这些细胞具有恢复受损细胞的能力，并有可能改变其身份以产生多种不同的细胞类型。这种特性使得研究人员试图在再生医学中使用这些细胞，在实验室中制造细胞，以取代我们体内受损的细胞。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细胞类型。部分答案是，它们的控制系统如何连接，以及它们的DNA如何包装。该项目将研究分子开关，称为FOXK 2-SIN 3A蛋白复合物，如何有助于这种重新布线过程。我们将在人类胚胎干细胞中进行研究，并检查这些细胞改变命运以产生不同细胞类型时发生的分子事件。我们的发现将帮助我们了解干细胞如何改变它们的身份，并可能为我们提供机制信息，使我们能够改善这一过程以获得治疗益处，并了解与年龄相关的疾病如何发展。

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.