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

这种原生动物寄生虫会引起东部牡蛎的“皮肤病”，并导致自然和养殖牡蛎数量的灾难性下降。这对北美大西洋和墨西哥湾沿岸的河口生态系统造成了严重破坏。因为铁是生长所必需的，细胞内寄生虫如P. marinus必须从宿主那里获得铁才能成功增殖。然而，直到最近，细胞内寄生虫摄取铁的机制仍然不清楚。研究证实了P. marinus对铁的增殖需求，并从寄生虫（PmNramp）及其牡蛎宿主（CvNramp）中克隆了铁转运蛋白Nramp （Nramp；天然耐药相关巨噬细胞蛋白）。这导致了一种假设，即PmNramp代表了一种铁摄取机制，使寄生虫能够在牡蛎宿主内成功入侵和增殖。该项目将使用分子、遗传和生化方法来表征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。预计这一项目将使人们对它们在与医学和兽医有关的寄生虫毒性中的作用有新的认识。鉴于牡蛎疾病的区域相关性，该项目具有重要意义，因为它将有助于开发新的干预策略来恢复自然和养殖牡蛎种群。从教育的角度来看，牡蛎。marinus系统非常适合与寄主-寄生虫生物学相关的基础科学原理的课堂整合，该项目将涉及来自巴尔的摩地区的本科生、高中生和教师，他们大多来自代表性不足的少数民族，既可以作为长凳上的实习生，也可以作为课堂上的实习生，通过诸如专家（NSF）、切萨皮克教师研究奖学金（NOAA）、生活教室、独创性、巴尔的摩社区学院，以及霍华德、乔治王子和巴尔的摩县的指导项目。

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.