Engineering myxobacterial super-predators to fight crop disease

植物病原微生物（phytopathogens）在全球范围内造成了巨大的经济损失，威胁着粮食安全。例如，仅在美国，青枯雷尔氏菌每年就造成价值超过10亿美元的马铃薯作物损失。为了减少收获前的浪费和提高粮食安全，迫切需要通过清除植物病原体来防治作物病害。粘细菌等捕食性细菌具有作为生物防治剂的潜力，因为它们可以捕食植物病原体，从而减少作物病害并促进植物生长。粘细菌能够捕食广泛的猎物微生物，包括病原细菌和真菌。虽然所有的粘细菌菌株有一个广泛的猎物范围，偶尔菌株表现出异常有效的捕食活动对特定的猎物。这种增强的捕食活性与菌株的遗传学无关，这表明负责增强捕食活性的基因是水平遗传的，而不是垂直遗传的。这种情况得到了基因组测序的支持，基因组测序表明粘细菌菌株具有小的“核心基因组”-每个菌株都拥有的基因。然而，大多数基因来自“辅助基因组”，这在很大程度上是独特的个别菌株。基因组之间的这种变异性可以用来识别负责捕食特定猎物的基因。当捕食基因被确定后，就有可能在菌株之间移植它们，以产生对特定猎物具有增强的捕食活性或对一系列猎物具有更广泛活性的“超级捕食者”菌株。超级捕食者菌株作为农业接种剂将是有利的，因为它们比环境菌株更能杀死植物病原体。本研究将验证一个假设，即移植猎物特异性捕食基因可以用来改变粘细菌捕食者的猎物范围，增强它们保护作物免受疾病侵害的能力，并增加作物产量。为了验证这个假设，比较基因组学将用于鉴定粘细菌中的猎物特异性捕食基因。捕食基因将在菌株之间移植，以增加对多种病原体的捕食活性。我们将专注于新的基因和那些编码消化酶/毒素，而不是那些导致抗菌化合物的生产。我们还将设计超级捕食者，以减少对PGPR（植物生长促进根际细菌）的捕食活动。然后将在植物中评估工程改造的“超级捕食者”保护作物免受疾病侵害和促进植物生长的能力。一个捕食性粘细菌属。这些菌株中大约有一半已经进行了基因组测序，这表明它们具有高度的个体性，具有较大的辅助基因组。菌株还表现出对一组猎物微生物（包括病原菌和真菌）的捕食活性的多样性模式，表明这些菌株中存在/不存在猎物特异性捕食基因。该学生奖学金位于遗传学，微生物学，植物生物学和生物信息学之间的界面，旨在轻轻地向学生介绍不断扩大的方法范围。项目小组将提供基因组分析、遗传工程、微生物技术、基因表达测量、植物病理学分析和生物信息学/计算方法等现代方法方面的全面培训。监督员还将提供关于使用先进的计算基础设施进行基因组分析的培训，例如国际地球资源局内部的高性能计算集群，以及通过威尔士超级计算。这些技能对生命科学和医学问题的适用性，使它们成为“一般性”的跨学科。

Plant pathogenic microbes (phytopathogens) cause huge economic losses and threaten food security globally. For example, Ralstonia solanacearum alone causes more than $1 billion worth of potato crop losses each year in just the USA. To reduce pre-harvest wastage and increase food security, there is an urgent need to fight crop disease by targeting the removal of phytopathogens. Predatory bacteria such as myxobacteria have the potential to be used as biocontrol agents for this purpose, as they can prey upon phytopathogens, thereby reducing crop disease and promoting plant growth.Myxobacteria are able to prey upon a broad range of prey microbes, including pathogenic bacteria and fungi. While all myxobacterial isolates have a broad prey range, occasional strains exhibit unusually effective predatory activity against specific prey. Such enhanced predatory activity does not correlate with strain phylogeny, which suggests that the genes responsible for enhanced predatory activity have been inherited horizontally rather than vertically.This scenario is supported by genome sequencing, which shows that myxobacterial strains have small 'core genomes' - genes which every strain possesses. However, the majority of genes come from the 'accessory genome', which is largely unique to individual strains. Such variability between genomes can be exploited to identify the genes responsible for predation of specific prey. When predation genes have been identified, it is then possible to transplant them between strains, to generate 'super-predator' strains with increased predatory activity against particular prey, or with a broader activity against a range of prey. Super-predator strains would be advantageous for use as agricultural inoculants, as they would be better able to kill phytopathogens than environmental strains.This studentship will test the hypothesis that transplantation of prey-specific predation genes can be used to alter the prey-range of myxobacterial predators, enhancing their ability to protect crops from disease and increasing crop yields.To test this hypothesis, comparative genomics will be used to identify prey-specific predation genes in myxobacteria. Predation genes will be transplanted between strains to increase predatory activity against multiple pathogens. We will focus on novel genes and those which encode digestive enzymes/toxins rather than those which cause the production of antimicrobial compounds. We will also engineer super-predators to have reduced predatory activity against PGPRs (plant growth promoting rhizobacteria). The ability of the engineered 'super-predator to protect crops from disease and to promote plant growth will then be assessed in planta.Previously, we isolated >80 strains of Corallococcus spp., a genus of predatory myxobacteria. Around half of those strains have now been genome-sequenced, which showed that they are highly individual with large accessory genomes. Strains also exhibited diverse patterns of predatory activity against a panel of prey microbes (including pathogenic bacteria and fungi), indicating the presence/absence of prey-specific predation gene in those strains.This studentship lies at the interface between genetics, microbiology, plant biology and bioinformatics, and has been designed to gently introduce the student to an ever-expanding range of methods. The project team will provide full training in modern methods of genomic analysis, genetic engineering, microbiological techniques, gene expression measurements, plant pathology assays and bioinformatics/computational methods. Training will also be provided by the supervisors in the use of advanced computational infrastructures for genomic analyses, such as the high performance computing clusters available within IBERS, and via Supercomputing Wales. The applicability of these skills to problems across the life and medical sciences, make them 'generically' cross-disciplinary.