Elucidation of serine hydroxymethyltransferase-mediated mechanisms of nematode disease resistance

阐明丝氨酸羟甲基转移酶介导的线虫抗病机制

• 批准号: 2152548
• 负责人: Lesa Beamer
• 金额: $ 62.41万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2152548&HistoricalAwards=false
• 关键词: Elucidation; serine; hydroxymethyltransferase; mediated; mechanisms

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.

大豆孢囊线虫（SCN）是一种微小的土传蛔虫，是大豆的广泛病原体，也是美国农业中的一个十亿美元的问题。几十年来，种植单一类型的遗传抗性导致这种病原体对商业上可获得的SCN抗性大豆品种的广泛毒力，降低了它们的总体有效性。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，并能够在大豆中设计更持久的抗性。研究人员将研究在一种大豆中发现的遗传差异，这种大豆与对SCN的抗性增加有关，但目前大豆生产商还没有广泛使用。这些基因变化影响了一种参与叶酸代谢的大豆酶，称为丝氨酸羟甲基转移酶8（SHMT 8）。使用科学方法的组合，包括结构生物学和基于植物的研究，SHMT 8的遗传差异对大豆植物的影响将被表征，并用于开发新的方法来对抗大豆田中的SCN侵染。这是两名具有互补专业知识的研究人员之间的合作努力：结构生物学和生物化学研究将在密苏里州大学进行，基于植物的研究将在格鲁吉亚大学进行。参与该项目的研究生和本科生研究人员将参加为期2周的体验式学习夏季交流计划，该计划在密苏里州和格鲁吉亚大学的PI实验室之间进行，以接触两个实验室的互补学科。包括妇女和代表性不足的少数民族在内的本科生将直接参与研究工作。每年夏天，针对K-5代表性不足的少数民族举办为期一周的线虫靴子夏令营，让研究生和本科生参与科学推广活动，以改善STEM教育。大豆胞囊线虫（SCN）是一种显微镜下的蛔虫，是大豆最重要的病原体。目前的管理几乎完全依赖于使用抗SCN大豆品种。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。该项目旨在提供对大豆SCN抗性基础的分子理解，从而能够开发更持久的抗性和对抗这种破坏性农业病原体的潜在新策略。具体而言，该项目将重点研究大豆酶丝氨酸羟甲基转移酶8（SHMT 8），该酶具有与SCN抗性相关的遗传差异：相对于SCN易感大豆品种中发现的SHMT 8，SHMT 8的“抗性版本”仅相差两个氨基酸。提出了SHMT 8的结构、生化和生物物理特性，以帮助阐明SHMT 8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，以阐明大豆根部响应SCN感染和影响大豆抗性的宿主途径的SHMT 8介导的代谢扰动。采用现代基因组编辑工具的基于植物的研究对于确认有关来自体外研究的SCN抗性的新假设也至关重要。除了对大豆农业（美国经济的重要组成部分）的益处外，该合作研究项目还涵盖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NSF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。