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: 1613462
• 负责人: Ron Mittler
• 金额: $ 84.54万
• 依托单位: University of North Texas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1613462&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 亿年前光合生物将氧气引入大气以来，活性氧（称为活性氧）一直是有氧生命不受欢迎的伴侣。尽管目前被植物和动物细胞用作重要的信号分子，但这些活化形式的氧可能对细胞和组织具有剧毒，并导致氧化损伤（氧化应激）。该项目由北德克萨斯大学的 Ron Mittler 和 Rajeev Azad 以及以色列耶路撒冷希伯来大学的 Rachel Nechushtai 领导，其长期目标是确定细胞如何监测细胞内的活性氧水平并防止其毒性。该项目将特别强调植物和动物细胞中活性氧调节的一个未知方面，即一组新发现的蛋白质利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。这项研究获得的结果可能会导致新方法的开发，以增强作物对干旱和高温等重要胁迫的耐受性或延缓衰老。此外，拟议的研究还可以识别新型植物化合物和蛋白质，以减轻氧化应激、衰老和癌症和糖尿病等不同疾病。 PI 将培训一些研究生和本科生，并与当地教育中心和博物馆合作，向 K-12 学生提供服务。PI 将研究一类新型 Fe-S 蛋白（NEET 蛋白）在维持植物和动物细胞中的活性氧稳态。鉴于其独特的簇特征，假设 NEET 蛋白利用其氧化还原活性不稳定簇来感知细胞中的 ROS 水平并调节改变细胞代谢的不同途径。该项目的具体目标是： 1. 对 NEET 蛋白水平和/或功能发生改变的植物和动物细胞进行比较信号和调控网络分析。 2. 识别植物和动物细胞的 NEET 相互作用组网络。 3.确定NEET蛋白在细胞中的定位/功能动态，并进行哺乳动物和植物细胞之间NEET蛋白的遗传互补研究。结合功能遗传学、蛋白质组学、先进成像、RNA-Seq 和网络分析方法，将寻求对细胞中 ROS/氧化还原传感/调节的机制理解。通过拟议的 NSF-BSF 合作确定的机制将在不同领域之间进行进一步比较：植物 - 通过 NSF 部分进行研究，动物 - 通过该项目的 BSF 部分进行研究，以获得 ROS/氧化还原传感/调节的进化视角这个美国/以色列合作项目得到了美国国家科学基金会和以色列两国科学基金会的支持。