Chromatin architecture and regulation

在人类细胞中，DNA，我们的基因蓝图，与蛋白质精确地折叠在一个称为染色质的复合体中。这有两个目的，一是保护DNA不受损害，二是在一个被称为转录的过程中，调节分子机器读取DNA的方式；读取DNA的错误会导致蛋白质改变，改变细胞功能。我们基因组中需要阅读的区域被称为基因，尽管我们进行了多年的研究，但我们并不了解DNA是如何在细胞内折叠的，特别是在被称为启动子和增强子的基因前面的专门区域。在这个项目中，我们将开发新的工具来绘制人类细胞中DNA/蛋白质的3D结构图，并创建高分辨率的基因组图。然后，我们将重点绘制已知对人类疾病重要的基因的特定启动子和增强子的结构，并确定控制启动子折叠和功能的分子机制。这个项目将提供对DNA如何在人类细胞中包装和调节的基本见解。这些信息将使我们能够随后调查染色质折叠在疾病中是如何改变的，并开发新的治疗方法来纠正这些改变。

In human cells, DNA, our genetic blueprint, is precisely folded with proteins in a complex called chromatin. This serves two purposes, to protect DNA from damage and to regulate how DNA is read by molecular machines, in a process called transcription; mistakes in reading DNA lead to altered proteins and change cell function. The regions of our genomes that need to be read are called genes and despite many years research we do not understand how DNA is folded up inside cells, particularly at the specialised regions in front of genes called promoters and enhancers. In this programme we will develop new tools to map the 3D structures of DNA/proteins in human cells and create a high resolution map of our genomes. We will then focus on mapping the structure of specific promoters and enhancers for genes that are well known to be important for human disease and identify the molecular mechanisms for controlling promoter folding and function. This project will provide fundamental insight into how DNA is packaged and regulated in human cells. This information will subsequently enable us to investigate how chromatin folding is altered in disease and to develop new therapies to correct these changes.