Engineering cereal immunity using structure-guided design of effector/host interactions.

每年，全球主要粮食作物的大量产量都因收获前植物病害而损失。这些疾病是由病原微生物引起的，如真菌、卵菌和细菌。这些产量损失是在世界对粮食需求不断增长的背景下发生的，随着世界人口的增长和饮食习惯的改变，粮食需求继续上升。这也是在气候变化对植物生长产生影响的背景下进行的。传统的植物育种方法和化学控制（通过杀菌剂和杀虫剂）可以帮助限制病原体对收获前作物产量的影响。然而，其中许多方法可能只有短期效果，或者由于生产和使用对环境的影响而不可持续。需要新的方法来控制植物疾病，而抗病的遗传形式为环境友好型可持续农业提供了潜力。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。病原体利用它们部署到植物细胞中的药剂来改变环境，使病原体受益，通常是通过与植物细胞成分相互作用。这些被称为“效应器”的药剂也可以暴露病原体的存在，因为植物免疫系统已经进化出受体来感知这些药剂的存在和/或活性。这些植物传感器可以通过直接接触效应器及其与宿主细胞成分的相互作用来工作，有点像握手，但具体如何发生的细节尚不清楚。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物，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。这种病原体还能引起大麦和小麦作物的严重疾病，因此是全世界关注的主要问题。我们已经定义了这些效应物之一与植物细胞成分之间“握手”的图像，然后被植物免疫系统感知。但这只是相互作用的一个缩影，我们需要通过对植物的生物化学和生物学研究来更好地理解这种相互作用的含义。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物与其靶向的植物细胞成分之间的握手有多强和特异性，以及这对免疫有多重要。作为其中的一部分，我们将对分子的形状做一些小的改变，看看这是如何影响相互作用的强度的。然后，我们将进行实验，对我们一直在研究的效应物家族的活性多样性提出问题，因为植物细胞中可能存在其他靶点。最后，在我们了解了握手在这个系统中形成的相互作用之后，我们将寻求设计这些相互作用，并观察这是否能提高水稻植物免疫系统的稳健性，但也看看我们是否能将抗病能力转移到大麦上，从长远来看，小麦。

Every year, significant yields of our key global food crops are lost to pre-harvest plant disease. These diseases are caused by pathogenic micro-organisms, such as fungi, oomycetes and bacteria. These yield losses are set against the world's increasing demands for food, which continue to rise as the world's population grows and there are changes in dietary habits. This is also set against the backdrop of the impact of climate change on plant growth. Traditional plant breeding approaches and chemical control (via fungicides and pesticides), can help limit the impact of pathogens on pre-harvest crop yield. However, many of these approaches may have only short-term effects, or are unsustainable due to the environmental impact of production and use. New ways to control plant diseases are required, and genetic forms of disease resistance offer the potential for environmentally friendly, sustainable agriculture. 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. Pathogens use agents that they deploy into plant cells to alter the environment for the benefit of the pathogen, usually by interacting with plant cell components. These agents, known as "effectors", can also give away the presence of the pathogen as the plant immune system has evolved receptors to sense the presence and/or activity of these agents. These plant sensors can work by directly contacting the effectors and their interactions with host cell components, a bit like a handshake, but the details of how this actually occurs are not well 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 an effector, 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. This pathogen can also cause serious disease of barley and wheat crops, so is a major concern around the world. We have defined a picture of the "handshake" between one of these effectors and a plant cell component, which is then sensed by the plant immune system. But this is just a snapshot of the interaction, and we need to understand the implications of the interaction much better using biochemistry and biological studies in plants. To do this we will use a number of experimental approaches. Firstly, we will define how strong and specific the handshake is between the pathogen effector and the plant cell component it targets, and how important this is for immunity. As part of this we will make small changes to the shape of the molecules and see how this affects the strength of the interaction. Then we will perform experiments to ask questions about the diversity of activity of the family of effectors we have been studying as there maybe additional targets in plant cells. Finally, after we understand the interactions formed by the handshakes in this system, we will seek to engineer these interactions and observe whether this improves the robustness of the plant immune system in rice, but to also see if we can transfer the disease fighting capability to barley and, in the longer term, wheat.