权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Evolutionary dynamics of zoonotic malaria

人畜共患疟疾的进化动力学

基本信息

批准号：
10639432
负责人：
Amy Goldberg
金额：
$ 66.67万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-25 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10639432
关键词：
Alouatta Americas Asia Back Binding Proteins Blood Cells Brazil Case Study Cell Surface Proteins Cells Clinical Complement Complex Computer Models Computing Methodologies Demography Development Drug Targeting Environment Erythrocytes European Evolution Face Future Gene Expression Gene Family Genes Genetic Genetic Variation Genome Genome Scan Genomics Goals Health Human Human Genome Infection Intervention Invaded Life Cycle Stages Location Malaria Methods Modeling Monkeys Parasites Pattern Phylogenetic Analysis Phylogeny Plasmodium Plasmodium falciparum Plasmodium vivax Population Population Genetics Predisposition Primates Proteins Publishing Recording of previous events Reporting Reticulocytes Risk Role Route Sampling Sexual Reproduction South America South American Southeastern Asia Specificity System Techniques Testing Transgenic Organisms Variant Work Zoonoses burden of illness cross-species transmission experimental study genetic evolution genetic signature genome resource genome sequencing genome-wide genomic data improved insight method development nonhuman primate novel offspring preference pressure protein structure simulation timeline tool transmission process whole genome

项目摘要

Dozens of malaria species, of the genus Plasmodium, infect human and nonhuman primates worldwide. At least eight of these parasite species have moved from primate reservoirs into human populations, including historical host expansion of P. vivax and P. falciparum, the two primary malaria-causing agents in humans worldwide. As we make progress towards elimination of these common malaria parasites, emerging host switches or expansions that introduce new or rare malaria parasites into human population are an increasing barrier to global elimination. Indeed, in parts of Southeast Asia, a zoonotic malaria parasite is now the main cause of clinical malaria. The lack of genomic resources for zoonotic malaria strains, particularly from wild primates, has been a major barrier to understanding the emergence of malaria parasites and their risk for spread in human populations. Using the emerging zoonotic parasite from Brazil, P. simium, as a case study, we combine whole-genome sequencing of multiple parasite and their host populations to characterize the genetic basis of host specificity and evolution in malaria parasites. P. simium is an ideal system because it is a close relative of the well-studied P. vivax, and importantly, has recently shifted host ranges twice, first from historical human P. vivax into primates, and more recently back into humans. To interpret this new genomic data, we will combine experimental techniques with development of a whole-genome simulation framework that incorporated aspects of parasite lifecycle to better interpret neutral genetic diversity. This opens up recent developments in simulation-based inference techniques that we will use to infer the population history of South American malaria parasites, the timing of zoonoses, and identify loci under selection in multiple hosts. The function of candidate loci identified from computational approaches will then be tested with a specially- developed transgenic line expressing P. simium genes and computational modeling of protein structures from host and parasites. In sum, we combine insights from parasite genomics with complementary analyses of whole genomes from their wild primate hosts—from computational methods development to functional experiments—giving insight into the selective pressures that parasites face inside hosts and host-specific susceptibility.

数十种疟疾，疟原虫属，感染世界各地的人类和非人类灵长类动物。在