Mechanisms of gene regulation by CSL-Notch

包括人类在内的所有动物的发育和健康取决于它们产生和维持正确的组织平衡。每个组织都由具有不同特征的细胞组成，这些细胞必须以正确的比例制造和保持。这背后有两个基本原则：细胞必须能够相互交流，并且为了响应这种细胞间的交流，每个细胞都必须转换其基因的活性，以产生适合其功能的特征库。我们的研究重点是细胞通讯的一个重要途径，即所谓的Notch途径，我们的目标是发现通过这一途径的信号如何引起基因活动的特定开关，以确保正确的细胞特征。这不仅对理解动物发育和健康的正常过程很重要，而且对通过不适当的Notch信号引起的疾病（如癌症）也很重要。基因由一个密码组成，由组成我们遗传物质的DNA的4个不同字母产生，它们在细胞中进一步包装，使它们或多或少地接近阅读这个密码的机器。必须有潜在的规则来决定（1）Notch信号是否能够访问特定的基因，以及（2）这种访问是否会导致基因的生产性结果。这些规则可能依赖于来自DNA密码的信息，以及基因在每种细胞中的包装方式。我们的目标之一是找出这些规则是什么。为了实现这一点，我们将采取计算（代码分析）和生物（调查基因）方法的组合。对于我们的模型，我们使用果蝇，因为所有这些过程在物种之间都是相似的，所以我们可以使用这种简单的昆虫来了解与人类相关的机制。此外，我们正在调查的问题，即基因获取和使用的规则，是生物学的基础。因此，我们通过调查所获得的工具和知识可能对破译遗传密码具有广泛的相关性。

The development and health of all animals, including humans, depends on them generating and maintaining the correct balance of tissues. Each tissue consists of cells with distinct characteristics and these must be made and maintained in the right proportions. Two fundamental principles underlie this: the cells must be able to communicate with each other and, in response to this between-cell communication, each must switch the activity of their genes to produce the appropriate repertoire of characteristics for their function. Our research focuses on one important pathway of cell communication, so-called Notch pathway, and we aim to discover how signals through this pathway cause specific switches in gene activities to ensure the correct cell characteristics are made. This is important not only for understanding the normal process of animal development and health, but also for diseases such as cancer that arise through inappropriate Notch signals.Genes consist of a code, generated from the 4 different letters that make up the DNA of our genetic material, and they are further packaged in the cell to make them more or less accessible to the machinery that reads this code. There must be underlying rules that determine (1) whether or not the Notch signal is able to access a particular gene and (2) whether that access results in a productive outcome from the gene. The rules are likely to rely on information from the DNA code and from the way that the gene is packaged in each type of cell. One of our goals is to find out what these rules are. To achieve this we will take a combination of computational (code analysis) and biological (surveying the genes) approaches. For our model we use the fruitfly, as all these processes are similar across species, so we can use this simple insect to learn about the mechanisms that are relevant to humans as well. In addition, the problem we are investigating, the rules governing gene access and usage, are fundamental to biology. The tools and knowledge that we generate through our investigations are therefore likely to have widespread relevance for deciphering the genetic code.