An evolutionary step ahead: developing synthetic immunity against plant-parasitic nematodes

向前迈出的进化一步：开发针对植物寄生线虫的合成免疫力

• 批准号: 2278943
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2278943
• 关键词: evolutionary; step; ahead; developing; synthetic

PhD project strategic theme: Bioscience for sustainable agriculture and foodPlant-parasitic nematodes threaten global food security and account for over 10% of the annual life-sustaining crop losses. The aim of my PhD is to develop a synthetic immune response against plant-parasitic nematode infection as a new tool to mitigate these losses.Plant pathogens are an increasing concern for global food security. Extensive use of monoculture has led to increased populations of pests, including plant-parasitic nematodes. Much research is focussed on finding and generating resistant crops. As part of the evolutionary arms-race with their host, plant-parasitic nematodes have evolved various strategies to evade and/or nullify the existing plant immune system (e.g. "effectors"). To get a step ahead in the arms-race, and increase the robustness of resistance we need an immune system that these parasites have not co-evolved with.The project will focus on the cyst nematode Heterodera schachtii, a sedentary endo-parasite that burrows into the root and parasitises a single cell. By regulating plant cell gene expression, it causes the host cell to re-differentiate into a syncytial feeding site. Once established, the survival of the nematode is dependent on this single cell: death of the cell means death of the nematode.Based on preliminary data of nematode infection we hypothesise that there is a unique transcriptional expression pattern associated with the formation of this feeding-site. We aim to utilise this unique pattern as a 'fingerprint' for nematode infection to drive circuits for selective cell death. The power of H. schachtii for testing these logic circuits lie in the ability to infect Arabidopsis thaliana in sterile tissue culture. This allows for rapid screening of circuits as genetic tools in this plant model are refined.To design and build synthetic immunity we need to investigate, understand and create the following: i) Refine the current dataset of H. schachtii infection for genes that uniquely describes feeding site formation in A. thaliana. ii) combining the dataset from objective i, with the extensive resources available for A. thaliana, identify, validate, and test promotor parts that are driven by nematode infection.; iii) construct synthetic logic circuits in A. thaliana using Boolean logic operators to detect nematode infection; and iv) Ultimately, utilise synthetic logic circuits to initiate programmed cell death and thus kill the nematode.In summary, my PhD aims to increase knowledge on the regulation of host genes which lie in the core of cyst nematode feeding site formation, use this knowledge to develop a more flexible immune system, and ultimately provide a proof-of-principle that could be applied to other plant diseases.

博士项目战略主题：可持续农业和食品寄生虫线虫的生物科学威胁着全球粮食安全，占年度维持生命的农作物损失的10％以上。我的博士学位是针对植物 - 寄生虫线虫感染发展合成免疫反应，作为减轻这些损失的新工具。植物病原体对全球粮食安全越来越关注。大量使用单一培养已导致包括植物寄生虫在内的害虫种群增加。许多研究的重点是发现和产生抗性作物。作为与宿主进化的武器竞赛的一部分，植物 - 寄生虫线虫已经进化了各种策略，以逃避和/或无效现有的植物免疫系统（例如“效应器”）。为了在武器竞赛中迈出一步，并提高了电阻的鲁棒性，我们需要一个免疫系统，这些寄生虫没有与之共同发展。该项目将重点放在囊肿线虫异质片Schachtii上，这是一种久坐的内部寄生虫，这是一个将其填充到根部并寄生在单个单元中。通过调节植物细胞基因的表达，它会导致宿主细胞重新分化为合成喂养位点。一旦建立，线虫的存活取决于这个单个细胞：细胞的死亡意味着线虫的死亡。基于线虫感染的初步数据，我们假设存在与这种饲料site形成相关的独特转录表达模式。我们旨在利用这种独特的模式作为线虫感染的“指纹”，以驱动选择性细胞死亡的电路。 H. schachtii测试这些逻辑电路的力量在于能够在无菌组织培养中感染拟南芥的能力。这可以使电路快速筛选作为该植物模型中的遗传工具。要设计和建立合成免疫，我们需要研究，理解和创建以下几点：i）完善当前H. schachtii感染的数据集，以唯一描述A. thaliana中的喂养部位形成的基因。 ii）将目标I的数据集结合在一起，以及可用于A. thaliana的广泛资源，识别，验证和测试由线虫感染驱动的启动子零件。 iii）使用布尔逻辑操作员在塔利亚纳（A. thaliana）中构建合成逻辑电路，以检测线虫感染； iv）最终，利用合成逻辑电路来启动编程的细胞死亡，从而杀死线虫。总而言之，我的博士旨在增加对位于囊肿线虫喂养部位形成核心的宿主基因的知识，利用这种知识来开发更灵活的免疫系统，最终可以提供一种验证的工厂，以便其他工厂供应其他疾病。