NSF/MCB-BSF: Integrating ROS, redox and cell metabolism across plant and animal cells

NSF/MCB-BSF：整合植物和动物细胞中的 ROS、氧化还原和细胞代谢

• 批准号: 1936590
• 负责人: Ron Mittler
• 金额: $ 66.47万
• 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: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1936590&HistoricalAwards=false
• 关键词: NSF; MCB; BSF; Integrating; ROS

Ever since the introduction of oxygen into the atmosphere by photosynthetic organisms, about 2.7 billion years ago, activated forms of oxygen (called reactive oxygen) have been the unwelcome companions of aerobic life. Although currently used by plant and animal cells as important signaling molecules, these activated forms of oxygen could be highly toxic to cells and tissues and cause oxidative injury (oxidative stress). The long-term goal of this project, led by Ron Mittler and Rajeev Azad of the University of North Texas and Rachel Nechushtai of Hebrew University in Jerusalem, Israel, is to determine how cells monitor their intracellular levels of reactive oxygen and prevent its toxicity. In particular, the project will highlight an unknown aspect of the regulation of reactive oxygen in plant and animal cells, namely the use of iron-sulfur clusters by a newly discovered group of proteins to monitor reactive oxygen levels and regulate cellular metabolism and other vital processes. Results obtained from this study could lead to the development of new and novel approaches to enhance the tolerance of crops to important stresses such as drought and heat or delay senescence. In addition, the proposed study could identify novel plant-based compounds and proteins that mitigate oxidative stress, aging and different diseases such as cancer and diabetes. The PIs will train a number of graduate and undergraduate students and partner with a local education center and museum to provide outreach to K-12 students.The PIs will investigate the role of a novel class of Fe-S proteins, NEET proteins, in maintaining ROS homeostasis in plant and animal cells. In light of their unique cluster features, it is hypothesized that NEET proteins use their redox-active labile clusters to sense ROS levels in cells and regulate different pathways that alter cellular metabolism. The Specific Aims of the project are: 1. Perform a comparative signaling and regulatory network analysis of plant and animal cells with altered level and/or function of NEET proteins. 2. Identify the NEET interactome network of plant and animal cells. 3. Determine the dynamics of NEET protein localization/ function in cells and conduct genetic complementation studies of NEET proteins between mammalian and plant cells. Using a combination of functional genetics, proteomics, advanced imaging, RNA-Seq and network analysis approaches, a mechanistic understanding of ROS/redox sensing/regulation in cells will be pursued. The mechanisms identified through this proposed NSF-BSF collaboration will be further compared between different kingdoms: plant - studied through the NSF part, and animal - studied through the BSF part of this project, to obtain an evolutionary perspective of ROS/redox sensing/regulation in cells.This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.

自从大约27亿年前通过光合生物将氧气引入大气中以来，活化形式的氧气（称为活性氧）一直是有氧生活的不受欢迎的伴侣。尽管目前被动植物和动物细胞用作重要的信号分子，但这些活化的氧气形式可能对细胞和组织剧毒，并引起氧化损伤（氧化应激）。该项目的长期目标是由北德克萨斯大学的罗恩·米特勒（Ron Mittler）和拉吉夫·阿扎德（Rajeev Azad）和以色列耶路撒冷希伯来语大学的雷切尔·尼古什（Rachel Nechushtai）领导，目的是确定细胞如何监测其细胞内反应性氧气水平并防止其毒性。特别是，该项目将突出植物和动物细胞中活性氧调节的未知方面，即通过新发现的蛋白质组使用铁硫簇来监测活性氧水平并调节细胞代谢和其他重要过程。从这项研究中获得的结果可能导致开发新的和新颖的方法，以增强农作物对重要压力（例如干旱，热或延迟衰老）的耐受性。此外，拟议的研究可以鉴定出新的基于植物性的化合物和蛋白质，以减轻氧化应激，衰老和癌症和糖尿病等不同疾病。 PI将培训许多研究生和本科生，并与当地的教育中心和博物馆合作，向K-12学生提供宣传。PIS将调查一种新型的Fe-S蛋白NEET蛋白质NEET蛋白质的作用，在维持动植物细胞中的ROS稳态中。鉴于其独特的簇特征，可以假设NEET蛋白使用其氧化还原活性不稳定簇在细胞中感知ROS水平并调节改变细胞代谢的不同途径。该项目的具体目的是：1。对NEET蛋白的水平和/或功能改变的动植物细胞进行比较信号传导和调节网络分析。 2。确定动植物细胞的NEET相互作用网络。 3。确定细胞中NEET蛋白定位/功能的动力学，并对哺乳动物和植物细胞之间的NEET蛋白进行遗传互补研究。使用功能遗传学，蛋白质组学，高级成像，RNA-seq和网络分析方法的结合，将采用对细胞中ROS/Redox感应/调控的机械理解。通过该拟议的NSF -BBF协作确定的机制将在不同王国之间进行进一步比较：通过NSF部分进行的植物和通过该项目的BSF部分进行了研究，以获得ROS/ISRAEL Project在US/ISRAECATIC PROVICATION PRACTICATION SCRICANTION ISRAECAINTIC PROCECTS SPARINCTIOND ISRAELICHIDENT和ISRAELI基金会支持ROS/REDOX传感/调节的进化观点。