The Role(s) of the Cation Transporter Nramp in the Intracellular Survival of Protistan Parasites

阳离子转运蛋白 Nramp 在原生生物寄生虫细胞内生存中的作用

• 批准号: 0958016
• 负责人: Gerardo Vasta
• 金额: $ 46.1万
• 依托单位: University of Maryland at Baltimore
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0958016&HistoricalAwards=false
• 关键词: Role; Cation; Transporter; Nramp; Intracellular

The protozoan parasite Perkinsus marinus causes "Dermo" disease in the eastern oyster, and is responsible for the catastrophic decline of natural and farmed oyster populations. This has resulted in severe damage to the estuarine ecosystem along the Atlantic and Gulf coasts of North America. Because iron is essential for growth, intracellular parasites such as P. marinus must acquire iron from their hosts for successful proliferation. Until recently, however, the mechanisms involved in iron uptake by intracellular parasites have remained obscure. The iron requirement for P. marinus proliferation has been demonstrated and the iron transporter Nramp (Nramp; Natural resistance-associated macrophage protein)cloned from both the parasite (PmNramp) and its oyster host (CvNramp). This has led to the hypothesis that PmNramp represents a mechanism for iron uptake that enables the parasite's successful invasion and proliferation within the oyster host. This project will use molecular, genetic, and biochemical approaches to characterize Nramp in P. marinus to gain insight into its role in virulence, and the impact of competition for iron on the outcome of the parasite/host interaction. it is anticipated that this project will lead to new insights into their role(s) in the virulence of parasites of medical and veterinary relevance. Given the regional relevance of oyster disease, this project is significant in that it will contribute to development of novel intervention strategies to restore natural and farmed oyster populations. From the educational standpoint, the oyster-P. marinus system is well suited for classroom integration of fundamental scientific principles related to host-parasite biology, and this project will involve the participation of undergraduates and high school students and teachers mostly from underrepresented minorities from the Baltimore area, both as interns at the bench and in the classroom, through training programs such as ExPERT (NSF), Chesapeake Teacher Research Fellowship (NOAA), Living Classrooms, Ingenuity, Baltimore Community College, and mentorship programs from Howard, Prince George, and Baltimore Counties.

原生动物寄生虫Perkinsus marinus导致东部牡蛎的“皮肤病”，并导致天然和养殖牡蛎种群的灾难性下降。这导致了对北美大西洋和墨西哥湾沿岸沿着河口生态系统的严重破坏。由于铁是生长所必需的，细胞内寄生虫如P. marinus必须从其宿主获得铁以成功增殖。然而，直到最近，细胞内寄生虫吸收铁的机制仍不清楚。已经证明了海泛毛虫增殖的铁需求，并且从寄生虫（PmNramp）和其牡蛎宿主（CvNramp）克隆了铁转运蛋白Nramp（Nramp;天然抗性相关巨噬细胞蛋白）。这导致了一种假设，即PmNramp代表了一种铁吸收机制，使寄生虫能够在牡蛎宿主中成功入侵和增殖。 该项目将使用分子，遗传和生物化学方法来表征P. marinus中的Nramp，以深入了解其在毒力中的作用，以及铁竞争对寄生虫/宿主相互作用结果的影响。预计该项目将导致对它们在医学和兽医相关寄生虫毒力中的作用的新认识。鉴于牡蛎疾病的区域相关性，该项目的意义在于，它将有助于开发新的干预策略，以恢复天然和养殖牡蛎种群。 从教育的角度来看，牡蛎-P. marinus系统非常适合于与宿主-寄生虫生物学相关的基本科学原理的课堂整合，该项目将涉及大部分来自巴尔的摩地区代表性不足的少数民族的本科生和高中生和教师的参与，无论是在板凳上还是在课堂上，通过ExPERT（NSF），切萨皮克教师研究奖学金（NOAA），生活教室，不安定，巴尔的摩社区学院，并从霍华德，乔治王子和巴尔的摩县的导师计划。