Parallel notch activation mechanisms provide robustness to developmental patterning in Drosophila

像人类和果蝇这样的多细胞生物是从单细胞增殖而来的。生物学中的一个重要问题是了解成人体内数百万个细胞是如何产生的。这些细胞必须在不同的组织中执行许多不同的功能，因此它们会分化成不同的细胞，例如心脏细胞或脑细胞。理解这种特化是如何发生的，以及每个特化细胞是如何在发育的正确时间在正确的位置出现的，这是生物学上的一个重要挑战。这不仅从增加我们的基础生物学知识的角度来看很重要，而且对我们对癌症、心脏病和痴呆症等疾病的理解也有重要意义。这是因为当我们遭受这类医疗问题时，控制生物体发育的信号往往是出错的信号。如果我们能够理解这些信号在发育过程中是如何正常运作的，那么这将为如何在这些信号出错时纠正它们的缺陷提供重要的见解。例如，有时癌症是由于一个信号被突变永久打开，而不是被调节打开和关闭而引起的。如果我们能找到一种方法，在不损害其正常功能的情况下阻断这些信号，那么就有可能治愈某些癌症。显然，通过人体实验来找到这些问题的答案在实践和伦理上都是困难的。然而，由于今天所有的生物体都是从一个共同的祖先进化而来的，因此通过研究其他生物体，就有可能理解与人类生物学和医学有关的问题。果蝇是一个强大的模型系统，经常被用来理解信号和发育问题。控制果蝇发育的主要信号在人类中是保守的，包括许多与人类疾病（如癌症）相关的信号。它是一种奇妙的模式生物，因为它很容易通过基因突变来操纵。这意味着我们可以研究完整组织中的信号，而不是试图通过研究培养皿中的分离细胞来推断它们的功能。后一种方法也非常有用，但可能会给出误导性的答案，除非它能与真实组织中的信号调查相结合。对果蝇的研究已经发现了许多在人类癌症中被错误调节的信号。我们的目标是研究一种由Notch蛋白介导的关键信号。这种蛋白质在发育和许多不同的组织中被多次使用。最著名的用途之一是在大脑发育过程中。Notch的功能是确保正确的特化细胞出现在身体的适当位置。我最近的研究发现，我们对这种受体如何工作的理解是不完整的。了解这一点非常重要，因为这种蛋白质在发育过程中被多次使用并且在许多类型的癌症中被错误调节。我们现在发现Notch有一种以前不知道的信号传递方式。该项目旨在通过识别这种新信号所需的成分，并找出它们在果蝇大脑和其他组织发育过程中的作用，来理解这种新信号。这项工作在帮助找到治疗癌症等疾病的方法方面具有巨大的潜力。它还可能有助于找到解决与衰老有关的问题的方法，并帮助我们过上更健康、更长寿的生活。这是因为Notch调节着干细胞，这些干细胞有助于在我们的一生中保持我们的组织和器官的健康。它还在脑细胞中起作用，帮助我们长时间记住事件。形成记忆能力的下降通常与老年痴呆症等与年龄有关的疾病有关。了解Notch的工作原理可能有助于未来解决这些具有挑战性的问题。

Multicellular organisms like humans and fruit flies, develop from the proliferation of a single cell. An important problem in biology is to understand how it is that the millions of cells present in the adult body arise. These cells have to perform many different functions in diverse tissues and therefore they become differently specialised, for example into heart cells or brain cells. It is an important challenge in biology to understand, not only how this specialisation occurs, but also how each specialised cell arises in the correct place at the correct time of development. This is not only important from the point of view of adding to our fundamental biological knowledge, but it has important implications for our understanding of diseases like cancer, heart disease and dementia. This is because the signals that control the development of the organism are often signals that go wrong when we are suffering such medical problems. If we can understand how these signals function normally in development then this will provide essential insight into how to correct defects in these signals when they go wrong. For example sometimes cancer is caused when a signal is switched on permanently by a mutation, rather being regulated on and off. If we can find a way to block such signals without harming its normal functions, then it might be possible to cure particular cancers. It is obviously difficult both practically and ethically, to find out the answers to these problems by experimenting on humans. However, because all living organisms today have evolved from a common ancestor, it is possible to understand problems related to human biology and medicine, by studying other organisms. The fruit fly is one powerful model system that is often used to understand problems of signalling and development. The major signals that control fruit fly development are conserved with humans, including many of the signals that are associated with human diseases such as cancer. It is a wonderful model organism because it is so easy to manipulate by making mutations in its genes. This means we can study signals in intact tissue rather than trying to deduce their function by studying isolated cells in a dish. The latter approach is also very useful but can give misleading answers unless it can be combined with the investigation of signalling in real tissues. Studying fruit flies has resulted in the identification of many signals that are misregulated in human cancers. Our aim is to investigate a critical signal that is mediated by a protein called Notch. This protein is used many times in development and in many different tissues. One of the most well known uses is during the development of the brain. The function of Notch is to ensure that correctly specialised cells arise in the proper places in the body. My research recently found out that our understanding of how this receptor works is incomplete. This is very important to know because this protein is used many times in development and it is misregulated in many types of cancer. We have now discovered that there is a way for Notch to signal that was not known before. This programme aims to understand this new signal by identifying its required components and finding out what they do during development of the fruit fly brain, and other tissues. The work has an enormous potential to help find ways to cure diseases like cancer. It may also help find ways to solve problems associated with aging and help us to lead healthier lives for longer. This is because Notch regulates stem cells and these contribute to keeping our tissues and organs healthy over our lifespan. It also functions in the brain cells to help us remember events for a long time. A decline in the ability to form memories is a problem often associated with age-related conditions such as dementia. Understanding how Notch works may help lead to solutions to these challenging problems in the future.