An effector-detector domain in a rice immune receptor: towards structure-guided design of new disease resistance proteins.

在每个生长季节，由于真菌、卵菌和细菌等病原微生物引起的疾病，世界上许多最重要的作物收成都遭受重大损失。这是在粮食需求不断增加的背景下发生的，随着世界人口的增长和饮食的变化，粮食需求继续增加。从传统的植物育种到化学控制（如杀菌剂/杀虫剂），有许多科学资源可以帮助限制病原体对作物产量的影响。然而，其中许多办法可能只有短期效果，或者在环境上是不可持续的。需要新的方法来控制植物病害。开发新的控制策略的一种方法是了解病原体如何引起疾病或逃避植物免疫系统检测的复杂机制。通过了解这些过程，我们可以找到方法来改造植物，帮助它们对抗感染。植物对抗感染的一种机制是检测试图改变植物细胞以使病原体受益的病原体。这些被称为“效应器”的药剂会泄露病原体的存在，而植物已经进化到能够感知这些病原体。这会引发植物的反应，帮助阻止感染的蔓延。植物传感器可以通过直接接触效应器来工作，就像握手一样，但其实际发生的重要细节尚不清楚。植物必须非常精确地知道病原体分子是否存在，而它可能需要的只是“手”的形状（想象一下，仅仅通过手的形状来识别10000人房间里的一个人）。如果植物细胞感知到效应器，它就会诱导细胞死亡，所以它必须做到正确。我们一直在研究一种微生物（真菌）的一系列病原体效应物之间的相互作用，这种微生物（真菌）会导致水稻（许多人赖以获取卡路里的主要粮食作物）发生毁灭性疾病。我们已经能够定义这些效应物之一与植物传感蛋白之间“握手”的性质。这只是相互作用的一个快照，我们需要利用植物的生物化学和生物学研究来理解它的含义。为了做到这一点，我们将使用一些实验方法。首先，我们将定义病原体效应器和植物传感器之间的握手有多强。其次，我们将对分子的形状做一些小的改变，看看这是如何影响握手的力度的。然后，我们将研究在自然界进化过程中这些病原体和植物分子发生的一些小变化，利用我们确定的握手的照片来帮助我们。我们也希望了解为什么病原体会产生它所产生的分子，我们会问这些分子在做什么。最后，在我们了解了这个系统中各种握手形成的相互作用之后，我们将设计一种植物传感器蛋白，它可以识别不止一种病原体分子，这可以给植物更好的抵御感染的机会。我们还将看看是否能将这种方法应用于水稻以外的植物，看看我们的新知识是否能帮助其他作物识别它们的病原体。

Every growing season, significant losses are realised to many of the world's most important crop harvests because of diseases caused by pathogenic micro-organisms, such as fungi, oomycetes and bacteria. This is against the backdrop of increasing demand for food, which continues to rise as the world's population grows and there are changes in diets. Many scientific resources, from traditional plant breeding to chemical control (e.g. fungicides/pesticides), are available to help limit the impact of pathogens on crop yield. However, many of these approaches may have only short-term effects or are environmentally unsustainable. New ways to control plant diseases are required. One way to develop novel control strategies is by understanding the intricate mechanisms of how pathogens cause disease or evade detection by the plant immune system. By understanding these processes we can develop ways to engineer plants to help them fight infection.One mechanism used by plants to fight infection is to detect pathogen agents that are attempting alter plant cells for the benefit of the pathogen. These agents, known as "effectors", give away the presence of the pathogen and plants have evolved to sense these. This triggers a response by the plant that helps stop the infection spreading. The plant sensors can work by directly contacting the effectors, like a handshake, but the important details of how this actually occurs are not known. The plant has to be very precise about knowing if a pathogen molecule is present, and all it may have to go on is the shape of the "hand" (imagine trying to identify one person in a room of 10,000 only by the shape of their hand). The plant cell will induce death of the cell if it senses the effectors, so it has to get it right. We have been studying the interactions of a set of pathogen effectors from a microorganism (fungus) that produces a devastating disease of rice, a major food crop that many people rely on for calories. We have been able to define the nature of the "handshake" between one of these effectors and a plant sensing protein. This is just a snapshot of the interaction, and we need to understand its implications using biochemistry and biological studies in plants. To do this we will use a number of experimental approaches. Firstly, we will define how strong the handshake is between the pathogen effector and plant sensor. Secondly, we will make small changes to the shape of the molecules and see how this affects the strength of the handshake. We will then investigate some small changes that have happened in these pathogen and plant molecules during evolution in nature, using the picture of the handshake we have determined to help us. We also wish to understand why the pathogen is producing the molecules it does, and we will ask questions about what these molecules are doing. Finally, after we understand the interactions formed by the various handshakes in this system, we will engineer a plant sensor protein that can recognise more than one pathogen molecule - which could give the plant a better chance of fighting off infection. We will also see if we can get this to work in a plant other than rice, to see if our new knowledge can help other crops recognise their pathogens.