Molecular Analysis of Plasmodium vivax Surface Antigens

间日疟原虫表面抗原的分子分析

• 批准号: 8274864
• 负责人: MARY R GALINSKI
• 金额: $ 54.88万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 2014-05-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274864
• 关键词: Adhesions; Apical; Binding; Binding Proteins; Biochemical; Bioinformatics; Biologic Characteristic; Biological; Biological Assay; Biological Models; Biology; Blood; Cells; Cellular biology; Characteristics; Clinical; Communities; Complement; Complex; Country; Databases; Development; Drug Delivery Systems; Erythrocytes; Experimental Models; Family; Future; Gene Expression Profile; Gene Proteins; Gene Targeting; Generations; Genes; Genetic; Genetic Recombination; Genetic Transformation; Genome; Human; Image; In Vitro; Infection; Intervention; Investigation; Knock-in Mouse; Knock-out; Knowledge; Label; Laboratories; Lead; Location; Malaria; Malaria Vaccines; Methodology; Methods; Modeling; Molecular; Molecular Analysis; Molecular Biology; Monoclonal Antibodies; Orthologous Gene; Parasites; Pharmaceutical Preparations; Plasmids; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Positioning Attribute; Post-Translational Protein Processing; Process; Proteins; Proteome; Proteomics; Public Health; Reagent; Research; Resolution; Resources; Rodent; Saimiri; Staging; Structure; Surface; Surface Antigens; Techniques; Technology; Testing; Toxoplasma; Training; Transfection; Vaccines; Vivax Malaria; asexual; base; comparative genomics; design and construction; experience; follow-up; functional genomics; genetic manipulation; genome database; global health; nonhuman primate; novel; polyclonal antibody; positional cloning; programs; protein complex; protein expression; research study; socioeconomics; tool; vaccine candidate

DESCRIPTION (provided by applicant): The broad long term objective of this project is to analyze and understand structurally and functionally the molecular make-up of Plasmodium vivax merozoites. This knowledge will identify and characterize proteins that may serve as important vivax malaria vaccine candidates or targets of anti-malaria drug interventions. Plasmodium vivax is a highly predominant malaria species, causing 80 million cases or more of malaria each year and major socioeconomic public health ramifications worldwide. Nevertheless, P. vivax is under investigated in part because it cannot be cultured reliably long term in vitro. Specialized expertise and non human primate resources are therefore required for in depth laboratory investigations on this human parasite species. Experimental models using P. vivax parasites and the related simian malaria species P. knowlesi and P. cynomolgi in non-human primates are fundamental to this research program. Plasmodium merozoites are very complex and there are many gaps in knowledge regarding the full scope of molecules involved in their adhesion to and entry into red blood cells. The specific aims of this research are to 1) Identify novel P. vivax genes encoding merozoite proteins with surface, organellar and apical locations, 2) Investigate structural and functional characteristics of P. vivax merozoite surface and apically localized proteins and protein complexes, and 3) Develop a P. vivax model for integrated transfection and reverse genetics investigations. This research capitalizes extensively on the recent availability of Plasmodium genome databases, utilizing bioinformatics, micro-arrays, proteomics, genetic manipulation strategies, high resolution imaging capabilities, functional adhesion and invasion assays, immunochemical methods and cell biological technologies. This research will reveal new P. vivax merozoite proteins, gain a fuller understanding of the structure and coordinated expression of specific merozoite proteins and develop new knowledge on protein complexes, post translational modifications and function. As priorities, this project will also provide reagents for the broader malaria research community and develop a P. vivax blood-stage transcriptome and merozoite proteome, which will be valuable for vivax research specifically, as well as comparative genomics research aimed to distinguish features that are distinctive to the biology of P. vivax or conserved among Plasmodium parasites. Project Narrative Plasmodium vivax is a major species of malaria, which causes an estimated 80 million or greater infections annually in about 60 countries. This project aims to discover and characterize the structure and function of merozoite proteins that facilitate the successful entry of this parasite species into red blood cells, and which can serve as future malaria vaccine or drug targets.

描述（由申请人提供）：该项目的广义长期目标是在结构和功能上分析和理解植物植物元素的分子组成。这些知识将识别和表征蛋白质，这些蛋白质可能是重要的抗麦芽疟疾疫苗或抗马拉里亚药物干预措施的靶标。疟原虫是一种高度的疟疾物种，每年造成8000万例或更多的疟疾病例，并且在全球范围内引起重大的社会经济公共卫生后果。然而，Vivax的部分研究部分是因为不能在体外长期可靠地培养它。因此，对这种人类寄生虫物种进行深度实验室调查需要专业知识和非人类灵长类动物资源。使用Vivax P.寄生虫和相关的邻虫疟疾物种P. knowlesi和P. cynomolgi中的实验模型是该研究计划的基础。元素元素非常复杂，关于其粘附与红细胞粘附并进入红细胞的全部分子范围的知识有很多差距。这项研究的具体目的是：1）确定编码具有表面，细胞器和顶端位置的蛋白蛋白的新型疟原虫基因，2）研究Vivax Merozoite表面以及顶端局部局部蛋白质和蛋白质复合物的结构和功能特征，以及3）为整合的转染和反向基因研究而开发了P. Vivax模型。这项研究大量利用了疟原虫基因组数据库的最新可用性，利用生物信息学，微观阵列，蛋白质组学，遗传操纵策略，高分辨率成像能力，功能性粘附和入侵测定，免疫化学方法和细胞生物学技术。这项研究将揭示新的Vivax Merozoite蛋白质，对特定蛋白蛋白的结构和协调表达有了更深入的了解，并发展有关蛋白质复合物，翻译后修饰和功能的新知识。作为优先事项，该项目还将为更广泛的疟疾研究界提供试剂，并开发植发于疟原虫的血阶段转录组和梅罗洛佐伊特蛋白质组，该蛋白质蛋白蛋白组对于Vivax研究而言是有价值的，旨在与质子孢子或质子孢子岩的生物学独特的比较基因组学研究具有独特的特征。 项目叙事疟原虫是疟疾的主要物种，在大约60个国家 /地区估计每年引起8000万或更高的感染。该项目旨在发现和表征梅洛罗齐蛋白蛋白的结构和功能，这些蛋白促进了该寄生虫物种成功地进入红细胞，并且可以用作未来的疟疾疫苗或药物靶标。

项目成果

Antigenicity and immunogenicity of Plasmodium vivax merozoite surface protein-3.

• DOI: 10.1371/journal.pone.0056061
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Bitencourt AR;Vicentin EC;Jimenez MC;Ricci R;Leite JA;Costa FT;Ferreira LC;Russell B;Nosten F;Rénia L;Galinski MR;Barnwell JW;Rodrigues MM;Soares IS
• 通讯作者: Soares IS

Phylogenetic analysis of CSP and MSP-9 gene sequences demonstrates the close relationship of Plasmodium coatneyi to Plasmodium knowlesi.

CSP 和 MSP-9 基因序列的系统发育分析表明，科氏疟原虫与诺氏疟原虫有密切的关系。

• DOI: 10.1016/s1567-1348(03)00007-8
• 发表时间: 2003
• 期刊: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
• 作者: Vargas-Serrato,Esmeralda;Corredor,Vladimir;Galinski,MaryR
• 通讯作者: Galinski,MaryR

Plasmodium coatneyi in rhesus macaques replicates the multisystemic dysfunction of severe malaria in humans.

恒河猴中的科氏疟原虫复制了人类严重疟疾的多系统功能障碍。

• DOI: 10.1128/iai.00027-13
• 发表时间: 2013
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Moreno,Alberto;Cabrera-Mora,Monica;Garcia,Anapatricia;Orkin,Jack;Strobert,Elizabeth;Barnwell,JohnW;Galinski,MaryR
• 通讯作者: Galinski,MaryR

In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax.

• DOI: 10.1084/jem.169.5.1795
• 发表时间: 1989-05-01
• 期刊: The Journal of experimental medicine
• 作者: Barnwell JW;Nichols ME;Rubinstein P
• 通讯作者: Rubinstein P

In silico Identification and Validation of a Linear and Naturally Immunogenic B-Cell Epitope of the Plasmodium vivax Malaria Vaccine Candidate Merozoite Surface Protein-9.

间日疟原虫疟疾疫苗候选裂殖子表面蛋白 9 的线性和天然免疫原性 B 细胞表位的计算机鉴定和验证。

• DOI: 10.1371/journal.pone.0146951
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Rodrigues-da-Silva,RodrigoNunes;MartinsdaSilva,JoãoHermínio;Singh,Balwan;Jiang,Jianlin;Meyer,EsmeraldaVS;Santos,Fátima;Banic,DalmaMaria;Moreno,Alberto;Galinski,MaryR;Oliveira-Ferreira,Joseli;Lima-Junior,JosuédaCosta
• 通讯作者: Lima-Junior,JosuédaCosta