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

每年，由于收获前的植物病害，我们的主要全球粮食作物都损失了相当大的产量。这些疾病是由致病微生物引起的，如真菌、卵菌和细菌。这些产量损失是与世界对粮食日益增长的需求相抵触的，随着世界人口的增长和饮食习惯的变化，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防治(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，这些方法中的许多可能只有短期影响，或者由于生产和使用对环境的影响而不可持续。需要控制植物病害的新方法，而抗病的基因形式为环境友好、可持续的农业提供了潜力。开发新的控制策略的一种方法是通过了解病原体如何导致疾病或逃避植物免疫系统的检测的复杂机制。通过了解这些过程，我们可以开发出各种方法来改造植物，帮助它们抵御感染。病原体使用它们部署到植物细胞中的制剂来改变环境，从而有利于病原体，通常是通过与植物细胞成分相互作用来实现的。这些被称为“效应器”的制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制剂的存在和/或活性。这些植物传感器可以通过直接接触效应器以及它们与宿主细胞组件的相互作用来工作，有点像握手，但这实际上是如何发生的细节还不是很清楚。植物必须非常精确地知道是否存在病原体分子，而它可能需要做的只是“手”的形状(想象一下，在一个有1万人的房间里，仅仅通过手的形状来识别一个人)。如果植物细胞感觉到效应器，它会导致细胞死亡，所以它必须正确地感知。我们一直在研究一组来自微生物(真菌)的病原体效应器之间的相互作用，这种微生物(真菌)会产生一种毁灭性的水稻疾病，水稻是许多人依赖于卡路里的主要粮食作物。该病原菌还可引起大麦和小麦等作物的严重病害，是世界各国普遍关注的问题。我们已经定义了这些效应器之一和植物细胞成分之间的“握手”图，然后植物免疫系统可以感知到这一点。但这只是这种相互作用的快照，我们需要更好地利用植物中的生物化学和生物学研究来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器和其目标植物细胞成分之间握手的强度和特异性，以及这对免疫有多重要。作为这一过程的一部分，我们将对分子的形状做一些小的改变，看看这如何影响相互作用的强度。然后，我们将进行实验，询问我们一直在研究的效应器家族活动的多样性，因为植物细胞中可能存在额外的靶标。最后，在我们了解了这个系统中握手形成的相互作用后，我们将寻求设计这些相互作用，并观察这是否改善了水稻植物免疫系统的健壮性，但也看看我们是否可以将抗病能力转移到大麦，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.