A synthetic biology approach to develop durable disease resistance in crops

今天活着的10亿人营养不良。病虫害造成的农作物损失是实现全球粮食安全的主要障碍。在发展中国家，病虫害占农作物损失的一半以上。在发达国家，由于欧盟的指令，农药、杀菌剂和其他农业化学品的使用受到严格限制。迫切需要新的、持久的、可持续的、“绿色”的控制措施。田间植物经常同时受到多种不同类型病原体的侵袭。其中一些来自地上(即马铃薯晚疫病菌)，另一些来自地下(即寄生在植物根部的微小线虫)。这两种病原体都将蛋白质“注入”植物，使植物机械运转，从而使自身受益，并帮助传播感染。这些蛋白质(称为效应物)经常与正常的作物蛋白质相互作用，并以某种方式对其进行修饰以帮助病原体。关键的研究问题仍然是：1)效应器如何修改宿主蛋白以促进感染？2)不同类型的病原体是否针对相同的宿主蛋白？3)我们对分子相互作用的理解能否允许我们破坏这种相互作用，从而有利于植物免疫？我的目标是确定病原体效应器是如何与植物蛋白质发生物理作用的，以便将变化引导到植物蛋白质上，从而使病原体不再能够操纵它们。为了实现这一目标，我提议苏格兰邓迪大学和诺里奇的约翰·因斯中心开展合作。邓迪大学植物科学部与詹姆斯·赫顿研究所一起致力于应用植物育种、病理学和生态学的各个方面，使基础研究能够很容易地转化为最终用户。约翰·英尼斯中心在结构生物学方面有丰富的经验，特别是在植物-病原体相互作用领域。将这些相辅相成的机构聚集在一起对于实现这些目标至关重要。潜在的应用和好处：拟议的工作将提供对病原体如何操纵和感染宿主的新理解。有了这样的理解，对特定植物蛋白进行知情的重新设计，使其不再成为病原体的靶标，将破坏和防止感染。被多个病原体靶向的蛋白质可能对成功感染非常重要。通过编辑植物DNA对这些进行修改，将有助于创建一种针对多种不同病原体使用杀虫剂的持久“绿色”解决方案。这有助于确保发展中国家和发达国家的粮食生产和安全。

A billion people alive today are undernourished. Crop losses due to pests and diseases are a major obstacle towards achieving global food security. In developing countries, pests and diseases account for up to half of crop losses. In developed countries, the use of pesticides, fungicides, and other chemicals for agriculture are heavily restricted due to EU directives. New, durable, sustainable, 'green' control measures are urgently needed. Plants in the field are often under simultaneous attack from many different types of pathogens. Some of these are from above ground (i.e. the potato late blight pathogen Phytophthora infestans), and some are from below ground (i.e. microscopic nematode worms that parasitise plant roots). Both types of pathogens 'inject' proteins into the plant to hi-jack plant machinery to benefit themselves and help spread infection. These proteins (known as effectors) often interact with normal crop proteins, and in some way modify them to help the pathogen. The key research questions remain:1) How do effectors modify host proteins to promote infection? 2) Do different types of pathogens target the same host proteins? 3) Can our understanding of the molecular interaction allow us to disrupt it, favouring plant immunity? I aim to determine how pathogen effectors physically interact with plant proteins in order to direct changes to the latter so that the pathogens can no-longer manipulate them. To accomplish this I propose a collaboration between the University of Dundee in Scotland and the John Innes Centre in Norwich. The University of Dundee Division of Plant sciences, together with the James Hutton Institute, aim to apply aspects of plant breeding, pathology and ecology to allow fundamental research to be readily translated to end-users. The John Innes Centre has extensive experience of structural biology, in particular in the area of plant-pathogen interactions. Bringing together these complementary institutes is vital to achieve the aims. Potential applications and benefits:The proposed work will provide a new understanding of how pathogens can manipulate and infect their host. With this understanding, the informed re-design of specific plant proteins so they can no-longer be targeted by pathogens will undermine and prevent infection. Proteins targeted by multiple pathogens are likely to be very important to successful infection. Modifying these by editing the plant DNA will help to create a durable 'green' solution to the use of pesticides against multiple different pathogens. This could help to ensure food production and security in developing and developed countries.