Elucidation of serine hydroxymethyltransferase-mediated mechanisms of nematode disease resistance

大豆囊线虫（SCN）是一种微小的土壤传播的蛔虫，是一种广泛传播的大豆病原体，也是美国农业中一个价值数十亿美元的问题。几十年来种植单一类型的遗传抗性导致这种病原体在市售的抗scn大豆品种上的广泛毒力降低了它们的整体有效性。该项目的目标是更好地了解大豆植物的抗性机制，以深入了解SCN如何能够适应克服它，并使大豆的抗性设计更加持久。研究人员将研究在一种大豆中发现的与抗SCN能力增强有关的遗传差异，但目前还没有广泛应用于大豆生产商。这些遗传变化影响了一种参与叶酸代谢的大豆酶，即丝氨酸羟甲基转移酶8 （SHMT8）。利用包括结构生物学和植物研究在内的科学方法，将鉴定SHMT8遗传差异对大豆植物的影响，并用于开发对抗大豆田SCN侵染的新方法。这是两位具有互补专业知识的研究人员之间的合作努力：结构生物学和生化研究将在密苏里大学进行，而基于植物的研究将在乔治亚大学进行。参与该项目的研究生和本科生研究人员将在密苏里大学和乔治亚大学的pi实验室之间参加为期两周的体验式学习暑期交流计划，以接触两个实验室的互补学科。本科生，包括女性和代表性不足的少数民族，将直接参与研究工作。每年夏天，针对K-5未被充分代表的少数民族的为期一周的线虫训练营将吸引研究生和本科生参与科学推广，以改善STEM教育。大豆囊线虫（soybean囊肿nematode， SCN）是一种微小的蛔虫，是大豆最重要的病原菌。目前的管理几乎完全依赖于抗SCN大豆品种的使用。不幸的是，随着时间的推移，这种方法已经变得不那么有效，因为线虫已经适应了市售的抗性大豆基因型。该项目旨在对大豆中SCN抗性的分子基础进行了解，从而能够开发更持久的抗性和潜在的新策略来对抗这种破坏性的农业病原体。具体而言，该项目将重点研究大豆丝氨酸羟甲基转移酶8 (SHMT8)，该酶具有与SCN抗性相关的遗传差异：在SCN敏感的大豆品种中，SHMT8的“抗性版本”与SHMT8相比仅存在两个氨基酸的差异。提出了SHMT8的结构、生化和生物物理特性，以帮助揭示SHMT8的分子差异如何转化为大豆的SCN抗性。这项工作将通过基于植物的研究来补充，以阐明shmt8介导的大豆根系代谢扰动对SCN感染的反应和影响大豆抗性的寄主途径。采用现代基因组编辑工具的基于植物的研究对于确认来自体外研究的关于SCN抗性的新假设也至关重要。大豆农业是美国经济的重要组成部分，除了对大豆农业有利外，该合作研究项目还涵盖了x射线晶体学、蛋白质化学、植物-病原体相互作用和大豆分子遗传学等领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The soybean cyst nematode (SCN), a microscopic soil-borne roundworm, is a widespread pathogen of soybean and a billion dollar problem in US agriculture. Decades of planting a single type of genetic resistance has led to widespread virulence of this pathogen on commercially available SCN-resistant soybean cultivars reducing their overall effectiveness. The goal of this project is to better understand the resistance mechanisms of the soybean plant to gain insight into how SCN are able to adapt to overcome it and enable the design of more durable resistance in soybean. The investigators will study the genetic differences found in a type of soybean linked with increased resistance to SCN, but currently not broadly available to soybean producers. These genetic changes affect a soybean enzyme involved in folate metabolism known as serine hydroxymethyltransferase 8 (SHMT8). Using a combination of scientific approaches, including structural biology and plant-based studies, the impacts of the genetic differences in SHMT8 on the soybean plant will be characterized and used to develop new ways to fight SCN infestations in soybean fields. This is a collaborative effort between two investigators with complementary expertise: the structural biology and biochemical studies will be performed at the University of Missouri and the plant-based studies will be conducted at the University of Georgia. Graduate and undergraduate researchers involved in the project will participate in a 2-week experiential learning summer exchange program between the PIs’ laboratories at the Universities of Missouri and of Georgia, to gain exposure to the complementary disciplines in both laboratories. Undergraduates, including women and underrepresented minorities, will directly participate in the research efforts. A week-long Nematode Boot Camp each summer targeting K-5 underrepresented minorities will engage graduate and undergraduate students in science outreach for improved STEM education.The soybean cyst nematode (SCN), a microscopic roundworm, is the most important pathogen of soybean. Current management relies almost exclusively on the use of SCN resistant soybean cultivars. Unfortunately, this approach has become less effective over time as nematodes have adapted to the commercially available resistant soybean genotypes. This project aims to provide a molecular understanding of the basis of SCN resistance in soybeans and thereby enable the development of more durable resistance and potentially novel strategies for combating this destructive agricultural pathogen. Specifically, this project will focus on studies of the soybean enzyme serine hydroxymethyltransferase 8 (SHMT8), which has genetic differences linked to SCN resistance: the “resistant version” of SHMT8 differs by only two amino acids relative to SHMT8 found in SCN susceptible soybean cultivars. Structural, biochemical and biophysical characterization of SHMT8 is proposed to help unravel how the molecular differences in SHMT8 translate to SCN resistance in soybean. This work will be complemented by plant-based studies to elucidate SHMT8-mediated metabolic perturbations in soybean roots in response to SCN infection and host pathways that affect soybean resistance. Plant-based studies employing modern genome editing tools will also be critical for confirming novel hypotheses regarding SCN resistance derived from the in vitro studies. In addition to benefits for soybean agriculture, a critical part of the U.S. economy, this collaborative research project spans the areas of X-ray crystallography, protein chemistry, plant-pathogen interactions, and soybean molecular genetics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.