CAREER: Understand effector biology in the species complex Fusarium oxysporum

病原真菌对农业生产力构成严重威胁。镰刀菌（Fusarium oxysporum）是一种子囊真菌，已知会导致100多种植物的维管枯萎病，包括番茄、棉花、西瓜和香蕉，每年造成数十亿美元的产量损失。Ma实验室的长期目标是了解镰刀菌发病机制和植物防御的分子机制，以促进抗病作物的发展。本项目将利用已建立的拟南芥尖孢菌致病系统研究尖孢菌的发病机制和植物防御机制。对这一重要病原体的深入了解将为土壤传播的真菌和植物宿主之间的相互作用提供新的见解。植物防御真菌病原体的先进知识将促进耐久抗病作物的发展。因此，该研究有可能改变许多遭受枯萎病的重要作物的全球疾病管理。利用该研究项目产生的数据和假设，PI将开发一种基于课程的本科生研究体验（CURE），作为马萨诸塞大学阿默斯特分校和多米尼加学院的本科课程的一部分。多米尼加学院是一所教学密集型学院，其学生中40%是第一代大学生，66%是女性，40%以上是少数民族学生。学生的参与也将为拟议的研究带来新鲜的思想，增加可重复性和推进科学。真菌效应物操纵宿主免疫，并对真菌-植物关系的结果做出重大贡献，从致病到互惠。这个CAREER项目将采用多种方法研究尖孢菌效应生物学，包括计算生物学、反向遗传学、定量生物物理学和实时图像分析。具体来说，该项目将首先使用反向遗传学对300个候选效应物的功能进行表征（目标1）。然后，将使用定量生物物理学和活细胞成像来监测功能重要的效应物，以追踪效应物的贩运（目标2）。最后，该项目将通过网络建模剖析效应调节（目标3）。按照逐步的方法，这个项目将通过一个大的数据集，最后集中在几个重要的效应器。该项目建立在跨学科合作的基础上，将引入定量生物物理学来研究真菌效应生物学。该方法将在细胞和分子水平上为真菌效应物与其寄主植物细胞之间的相互作用提供前所未有的、定量的和透明的信息。本CAREER项目的主要教育目标是创建一门本科课程，学生可以在其中测试Aim 3中产生的假设，并通过将ChIPseq整合到我们的本科课程中，将真实的研究带入本科教育。

Pathogenic fungi pose serious threats to agricultural productivity. Fusarium oxysporum, an ascomycete fungus, is known to cause vascular wilt in over 100 plant species, including tomato, cotton, watermelon and banana, resulting in billions of dollars annual yield loss. The Ma lab's long-term goal is to understand the molecular mechanisms underlying Fusarium pathogenesis and plant defense for the development of disease resistant crops. This CAREER project will study both pathogenesis of F. oxysporum and plant defense using an established F. oxysporum - Arabidopsis pathosystem. A deeper understanding of this important pathogen will provide novel insights into interactions between soil-borne fungi and plant hosts. The advanced knowledge of plants defense against fungal pathogens will facilitate the development of durable disease-resistant crops. Therefore the research has the potential to transform world-wide disease management of many important crops that suffer from Fusarium wilts. Using the data and hypotheses generated from this research program, the PI will develop a Course-Based Undergraduate Research Experience (CURE) as part of the undergraduate curriculum at both UMass Amherst and Dominican College, a teaching intense college, whose students are 40% first generation college students, 66% women and over 40% minority students. Student participation will also bring fresh minds into the proposed research, increase the reproducibility and advance science. Fungal effectors manipulate host immunity and contribute significantly to the outcomes of fungal-plant relationships, ranging from pathogenic to mutualistic. This CAREER project will study F. oxysporum effector biology taking diverse approaches that include computational biology, reverse genetics, quantitative biophysics and live image analysis. Specifically, this project will first characterize function of 300 candidate effectors using reverse genetics (Aim 1). Then, functionally important effectors will be monitored to trace effector trafficking using quantitative biophysics and live cell imaging (Aim 2). Finally the project will dissect effector regulation through network modeling (Aim 3). Following a step-wise approach, this project will funnel through a large dataset and finally focus on a few important effectors. Built on an interdisciplinary collaboration, the project will introduce quantitative biophysics into the investigation of fungal effector biology. This approach will provide unprecedented, quantitative and transparent information at the cellular and molecular level on the interactions between fungal effectors and their host plant cells. A major Educational Objective of this CAREER project is to create an undergraduate course in which students test hypotheses generated in Aim 3 and bring authentic research into undergraduate education by integrating ChIPseq into our undergraduate curriculum.