Employing AI-guided approaches to discover and engineer plant disease resistance proteins

植物病害威胁着我们的食物供应。病原体可以使农作物减产30%，造成数千亿美元的损失。亏损可能会养活数十亿美元。全球贸易、气候变化和植物病原菌降低抗病能力的趋势增加了植物病害的爆发。预计到2050年，人口将达到90亿，粮食产量必须增加70%才能满足全球的饥饿。在这里，我们提出了一种人工智能引导的合成生物学方法来发现和设计具有新的抗病基因特异性的植物免疫受体。为此，我们与Resurrect BIO建立了合作伙伴关系，结合我们在植物免疫学方面的专业知识，实施了一条人工智能引导的管道。我们将首先建立一个自动化的机器学习管道，从植物病原体基因组中生成配体-受体复合体的数字资料库。下一步，将使用AF2-多聚体筛选感兴趣的配体以识别候选受体，随后将通过遗传和生化方法进行验证。然后，我们将把个体受体转化为缺乏它们的植物物种，作为对工程抗病概念的证明。然而，一些病原体编码感兴趣的配体的毒力等位基因，使它们能够避免免疫识别。我们将通过基因组调查从致病毒株的基因组中鉴定这些配体，并在相应的受体接口上进行必要的突变，以扩大它们的抗药性谱。我们的商业合作伙伴，Resurrect Bio，专门发现和修正被击败的抗病性状，然后将使用基因组编辑方法将这些特征引入感兴趣的作物

Plant diseases threaten our food supply. Pathogens can reduce crop yields by 30%, costinghundreds of billions of dollars. Losses could feed billions. Global trade, climate change, and plantpathogens' tendency to reduce disease resistance have increased plant disease outbreaks.Population is expected to reach 9 billion by 2050, and food production must increase by 70% toprevent global hunger.Here we propose an AI-guided synthetic biology approach to discover and engineer plant immunereceptors with new disease resistance gene specificities. To this end we formed a partnership withResurrect bio, to implement an AI-guided pipeline combined with our expertise in plantimmunology. We will first establish an automated machine learning pipeline to generate digitallibraries of ligand-receptor complexes from plant-pathogen genomes. Next, ligands of interest willbe screened using AF2-multimer to identify candidate receptors, which will be subsequentlyvalidated through genetic and biochemical approaches. We will then transform individualreceptors into plant species that lack them, as a proof of concept for engineering diseaseresistance. However, some pathogens encode virulent alleles of the ligands of interest, enablingthem to avoid immune recognition. We will identify such ligands from genomes of the virulentpathogen strains through genomic surveys and make necessary mutations in the correspondingreceptor interfaces to expand their resistance spectrum. Our business partners, Resurrect Bio,specialized to discover and amend defeated disease resistance traits will then employ genome-editing approaches to introduce these traits in the crops of interest