Multi-Omics Characterization of Plasmodium Vivax Hypnozoites

间日疟原虫休眠子的多组学表征

• 批准号: 10565802
• 负责人: David Serre
• 金额: $ 72.51万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-22 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565802
• 关键词: ATAC-seq; Acute; Africa; Anatomy; Biological; Biological Assay; Biological Markers; Biology; Cambodia; Cambodian; Cells; Clinical; Collection; Culicidae; Custom; Data; Endogenous Factors; Epigenetic Process; Falciparum Malaria; Foundations; Gene Expression; Gene Expression Profiling; Genetic Transcription; Hepatic; Hepatocyte; Human; Immune response; In Vitro; Infection; Knowledge; Laboratories; Liver; Location; Maintenance; Malaria; Malaria Vaccines; Messenger RNA; Metabolic; Methods; Modeling; Molecular; Monkeys; Organ; Organism; Outcome; Parasites; Patients; Plasmodium falciparum; Plasmodium vivax; Population; Populations at Risk; Prevalence; Process; Regulation; Relapse; Research; Role; Saimiri; Salivary Glands; Solid; Sporozoites; Testing; Tissues; United States National Institutes of Health; Variant; Vivax Malaria; Work; biomarker identification; cell type; clinically relevant; epigenomics; gene complementation; human pathogen; humanized mouse; improved; in vitro Assay; in vitro Model; in vivo; infection risk; insight; lipidomics; liver development; mass spectrometric imaging; multiple omics; nano; nonhuman primate; novel; novel therapeutic intervention; prevent; resilience; response; single-cell RNA sequencing; specific biomarkers; transcriptome sequencing; transcriptomics; vector

Abstract Plasmodium vivax parasites threaten half of the world’s population and are surprisingly resilient to on-going malaria elimination efforts, partially due to their ability to remain dormant in the liver as hypnozoites for weeks or months. Here, we propose to conduct state-of-the-art transcriptomic, epigenomic and lipidomic analyses using materials collected from non-human primates infected with P. vivax, and in vitro infections of human hepatocytes with patient-derived P. vivax sporozoites. Our analyses will provide a comprehensive perspective on the molecular and cellular mechanisms underlying the onset, maintenance and exit of P. vivax dormancy, and well as on the response of the host, from the infected hepatocytes to the organ- and organism-wide responses. Our findings will not only provide a better understanding of the fundamental processes underlying the fate and development of liver-stage P. vivax parasites but will also provide a solid foundation to develop better malaria vaccines and therapies against this important but understudied human pathogen.

摘要