Engineering gene regulatory networks to design disease-resistant crops

侵染植物的真菌造成重大的作物损失。即使采取了化学防治措施，它们在收获前造成的损失仍占作物损失的20%，在收获后造成的损失又高达20%。迫切需要具有抗感染能力的植物品种，以减少化学品的使用，并对抗对当前作物保护产品具有抗性的新出现的真菌菌株。然而，植物对许多这些致病真菌的抗性基础是高度复杂的，涉及许多基因，这些基因相互交叉调节，并影响许多下游基因的疾病进展。在之前的工作中，我们已经确定了一个介导生菜对真菌病原体抗性的基因网络。重要的是，我们还证明了这个网络中的几个基因也会影响植物谱系的抗病能力。在这个项目中，我们将通过应用计算模型来为该网络的工程提供信息，从而解决开发抗病作物的挑战。这将使我们能够预测哪种重新布线策略将最大限度地提高植物对感染的抵抗力，并最大限度地减少对其他作物性状（如大小、形状和营养价值）的影响。我们将使用几种遗传技术来设计植物的抗性，因为这些技术将为我们提供有价值的数据，使我们能够更好地了解植物对病原体的反应。然而，我们的目标是通过使用精确的基因编辑工具将小突变引入基因组的调控区域来确定一种赋予抗性的策略。我们将与我们的工业合作伙伴分享这一策略，使其能够在商业生菜品种中进行测试。在颁奖期间，我们将与业界、政策制定者和公众就我们的项目和作物生物技术进行交流。我们还将把该项目开发的所有知识、工具、方法和工作流程提供给英国研究界，使其能够应用于其他作物性状。

Plant-infecting fungi cause major crop losses. They are responsible for ~20% of crop losses before harvest, even when chemical control measures are used, and a further ~20% post-harvest. Plant varieties with resistance to infection are urgently required to reduce the use of chemicals and to combat emerging fungal strains that are resistant to current crop protection products. However, the basis of plant resistance against many of these pathogenic fungi is highly complex, involving many genes, which cross-regulate each other and numerous downstream genes to influence disease progression. In previous work, we have identified a network of genes that mediates resistance to fungal pathogens in lettuce. Importantly, we have also shown that several genes within this network also impact disease resistance across plant lineages. In this project, we will address the challenge of developing disease-resistant crops by applying computational modelling to inform the engineering of this network. This will allow us to predict which re-wiring strategies will maximise plant resistance to infection and minimise any impact on other crop traits such as size, shape and nutritive value. We will use several genetic techniques to engineer resistance into plants as these techniques will provide us with valuable data, enabling us to better understand plant responses to pathogens. However, we aim to identify a strategy for conferring resistance via the use of precision gene editing tools to introduce small mutations into the regulatory regions of the genome. We will share this strategy with our industrial partner to enable this to be tested in a commercial variety of lettuce. During the award, we will communicate with industry, policy-makers, and the general public about our project and crop biotechnology in general. We will also make all the knowledge, tools, methods and workflows developed in this project available to the UK research community to enable their application to other crop traits.