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，是从单个细胞的增殖发展而来的。生物学中的一个重要问题是理解存在于成人体内的数百万细胞是如何产生的。这些细胞必须在不同的组织中执行许多不同的功能，因此它们变得不同的专门化，例如转化为心脏细胞或脑细胞。这是生物学中的一个重要挑战，不仅要了解这种特化是如何发生的，而且要了解每个特化细胞是如何在正确的发育时间出现在正确的地方的。这不仅从增加我们的基本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的影响。这是因为控制生物体发育的信号往往是当我们遭受这样的医疗问题时出错的信号。如果我们能够理解这些信号在开发中如何正常运行，那么这将为在这些信号出错时如何纠正它们中的缺陷提供必要的洞察。例如，有时癌症是由突变永久开启一个信号而引起的，而不是被调节开和关。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种信号，那么就有可能治愈特定的癌症。显然，通过在人体上进行实验来找到这些问题的答案，在实践上和伦理上都是困难的。然而，因为今天所有的生物都是从一个共同的祖先进化而来的，所以通过研究其他生物来理解与人类生物学和医学有关的问题是可能的。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身上是保守的，包括许多与人类疾病有关的信号，如癌症。它是一个很棒的模式生物，因为它很容易通过对其基因进行突变来操纵。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，除非它能与对真实组织中信号传递的研究结合起来。对果蝇的研究已经发现了许多在人类癌症中被错误调控的信号。我们的目标是研究一种由一种名为Notch的蛋白质介导的关键信号。这种蛋白质在发育和许多不同的组织中被多次使用。最广为人知的用途之一是在大脑发育期间。Notch的功能是确保在身体的适当位置出现正确的特化细胞。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。知道这一点非常重要，因为这种蛋白质在发育过程中被多次使用，它在许多类型的癌症中被错误地调节。我们现在发现，Notch有一种方法可以发出以前不知道的信号。这个项目旨在通过识别其所需的成分，并找出它们在果蝇大脑和其他组织发育过程中的作用，来理解这种新的信号。这项工作具有巨大的潜力，可以帮助找到治愈癌症等疾病的方法。它还可能有助于找到解决与衰老相关的问题的方法，并帮助我们过上更健康的生活更长时间。这是因为Notch调节干细胞，这些干细胞有助于我们的组织和器官在我们的一生中保持健康。它还在脑细胞中发挥作用，帮助我们长时间记忆事件。形成记忆的能力下降是一个问题，通常与年龄相关的疾病，如痴呆症有关。了解Notch的工作原理可能有助于在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.