Plasmodium sporozoites and the mosquito

疟原虫子孢子和蚊子

• 批准号: 7010712
• 负责人: Brenda T Beerntsen
• 金额: $ 35.89万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010712
• 关键词: Culicidae; Plasmodium; SDS polyacrylamide gel electrophoresis; functional /structural genomics; gene expression; gene targeting; genetic translation; immunologic substance development /preparation; information retrieval; laboratory rabbit; liquid chromatography mass spectrometry; malaria; mass spectrometry; matrix assisted laser desorption ionization; molecular biology information system; parasite infection mechanism; parasitism; protein localization; protein signal sequence; proteomics; protozoal antigen; protozoal genetics; salivary glands; secretory protein; spores

DESCRIPTION (adopted from the application): Sporozoites exhibit infectivity for both mosquito salivary glands and vertebrate host tissues, and therefore they are a critical stage in the development of the parasite that can be exploited in efforts to control or eradicate malaria. New control measures involving vaccines, drug therapy and novel mosquito control methods are needed, and efforts toward this end have been expedited with the recent genomic and proteomic advances in the field of malaria research. This application describes an in silico, or data "mining" approach to selecting novel Plasmodium falciparum sporozoite genes that are translationally expressed in sporozoites, that contain a signal peptide sequence, and that are predicted, via sequence analysis, to be on the surface of or secreted by sporozoites. The hypothesis of this research is that the selected genes expressed by the sporozoite play a role in invading the vector and/or vertebrate host tissues. The specific aims of this research are the following: (1) to determine the cellular location of the proteins encoded by the three P. falciparum sporozoite genes that are selected following mining of PlasmoDB, and likewise to characterize Pf4, a homolog of Pg4 that is a surface molecule on P. gallinaceum sporozoites; (2) to perform a functional analysis of the four selected sporozoite genes using gene knock-out technology; and (3) to compare the proteome profiles of the mutant P. falciparum sporozoites with the wild-type strains to determine the impact of the selected genes on other gene products and pathways in the sporozoite. This research should elucidate the function of the four selected genes and help to identify their roles in sporozoite biology. In addition, a beginning will be made to assess the impact of the selected genes on other genes and processes or pathways in the sporozoite using state-of-the-art proteomic technologies. Ultimately, potential vaccine candidates and/or molecules that could be used to genetically manipulate the mosquito vector to prevent disease transmission could be discovered and eventually exploited to provide new additions to the arsenal of weapon available to better control malaria.

描述（从应用中采用）：孢子菌对蚊子型唾液腺和脊椎动物宿主组织都表现出感染性，因此它们是寄生虫发展的关键阶段，可以在控制或消除疟疾的努力中被利用。需要采取涉及疫苗，药物治疗和新型蚊子控制方法的新的控制措施，并且在疟疾研究领域的最新基因组和蛋白质组学进步加快了这一目的的努力。该应用描述了选择一种新型的恶性疟原虫孢子岩基因中的数据“挖掘”方法，该基因在孢子岩中翻译表达，该基因包含信号肽序列，并通过序列分析预测，以序列分析在Sporozoite的表面上进行序列分析。这项研究的假设是，孢子岩表达的所选基因在入侵载体和/或脊椎动物宿主组织中起作用。这项研究的具体目的如下：（1）确定由plasmodb挖掘后选择的三个恶性疟原虫孢子岩基因编码的蛋白质的细胞位置，并同样表征PF4，PF4是PG4的同源物，是P. gallinaceum sporozoite上的表面分子； （2）使用基因敲除技术对四个选定的孢子岩基因进行功能分析； （3）比较突变的恶性疟原虫孢子岩与野生型菌株的蛋白质组谱，以确定所选基因对孢子岩中其他基因产物和途径的影响。这项研究应阐明四个选定基因的功能，并有助于鉴定其在孢子岩生物学中的作用。此外，将开始使用最先进的蛋白质组学技术来评估所选基因对孢子岩中其他基因和过程或途径的影响。最终，可以发现可用于操纵蚊子载体以防止疾病传播的潜在候选疫苗和/或分子，并最终被利用，以为可用的武器库提供新的补充，以更好地控制疟疾。