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

原生动物寄生虫Perkinsus marinus会在东部牡蛎中引起“德尔莫”病，并导致自然和养殖牡蛎数量的灾难性下降。这对北美洲大西洋和海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，所以细胞内的寄生虫，如海洋假单胞菌，必须从它们的宿主那里获得铁才能成功繁殖。然而，直到最近，细胞内寄生虫摄取铁的机制仍然不清楚。已有研究表明，马利氏疟原虫的增殖需要铁，并从该寄生虫(PmNramp)及其牡蛎宿主(CvNramp)中克隆了铁转运蛋白Nramp(Nramp；天然抗性相关巨噬细胞蛋白)。这导致了一种假设，即PmNramp代表了一种铁摄取机制，使寄生虫能够在牡蛎宿主内成功入侵和增殖。本项目将使用分子、遗传和生化方法来表征海洋拟青霉中的Nramp，以深入了解它在毒力中的作用，以及竞争铁对寄生虫/宿主相互作用结果的影响。预计该项目将导致对它们(S)在与医学和兽医相关的寄生虫的毒力中所起的作用的新的见解。鉴于牡蛎病的区域相关性，该项目具有重要意义，因为它将有助于制定新的干预战略，以恢复自然和养殖的牡蛎种群。从教育的角度来看，牡蛎-P。Marinus系统非常适合与宿主-寄生虫生物学相关的基本科学原理的课堂整合，该项目将包括来自巴尔的摩地区未被充分代表的少数族裔的本科生、高中生和教师，作为法官和课堂上的实习生，通过培训计划，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，以及来自霍华德、乔治王子和巴尔的摩县的指导计划。

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.