Characterisation of Notch asparaginyl hydroxylation by FIH-1.

我们体内的细胞会收到许多信号，告诉它们什么时候生长，什么时候变成另一种细胞类型，确切地说是什么类型，甚至是如何应对低氧等情况。这些信号和细胞反应在胚胎发育过程中非常重要，当这些信号导致单个细胞成为完整的人时，成年人也是如此。在胚胎中，干细胞非常重要，在成人中也是如此，因为它们可以成为许多不同种类的细胞，这取决于身体需要什么。当信号不能正常工作时，它们会导致重大问题和疾病，从出生缺陷到癌症。Noch是一种重要的蛋白质，参与接收和传递某些信号，存在于各种生物体中，如蠕虫和人类。它告诉细胞，特别是干细胞和其他类似的细胞，何时以及如何从一种类型的细胞转变为另一种类型的细胞。例如，在从单个前体细胞产生许多不同类型的血细胞方面，它是非常重要的。Noch还与癌症等人类疾病有关，癌症是一种信号错误，细胞不断繁殖失控的疾病，还有某些类型的心脏病。另一种名为FIH的蛋白质是一种氧气传感器，当周围没有足够的氧气时，它会向细胞发出信号。FIH还被认为与癌症和心脏病有关。我们最近发现的证据表明，FIH也可以影响Notch蛋白的活性。这意味着氧气水平可能会对干细胞和Notch控制的其他过程产生影响，并且可能在癌症和其他疾病中非常重要。这个项目将首先确认FIH和Notch之间的联系。有许多不同的Notch蛋白，所以我们将看看这种连接是否与所有这些蛋白都起作用。它还将试图计算出这种联系的后果以及它的重要性。最后，可能对人类疾病造成的生物学后果，特别是癌症。

Cells within our body receive numerous signals telling them when to grow, when to turn into another cell type and exactly what type, and even how to respond to situations like low oxygen. These signals and cells response are very important during embryonic development, when these signals cause a single cell to become a complete person, and also in adults. Here in the embryo, and also in adults, stem cells are very important because they can become many different kinds of cells, depending on what the body needs. When the signals don't work properly, they cause major problems and diseases, from birth defects, to cancer. Notch is an important protein involved in receiving and passing on certain signals, and is found in organisms as diverse as worms and humans. It tells cells, especially stem cells and other similar cells, when and how to change from one type of cell to another. For example, it is very important in the generation of many different types of blood cells from a single precursor cell. Notch has also been implicated in human diseases such as cancer, where signalling goes wrong and cells keep multiplying out of control, and also certain types of heart disease. Another protein, called FIH, is an oxygen sensor that signals to the cell when there is not enough oxygen around. FIH has also been implicated in cancer and heart disease. We have recently found evidence suggesting that FIH can also influence the activity of the Notch proteins. This means that oxygen levels can potentially have an effect on stem cells and other processes controlled by Notch, and may be very important in cancer and other diseases. This project will first confirm the connection between FIH and Notch. There are a number of different Notch proteins, so we will see if this connection works with all of them. It will also try and work out the consequence of this connection is and how important it is. Finally, the likely biological consequences on human diseases, specifically cancer.