Malaria parasite determinants of host cell tropism
疟疾寄生虫宿主细胞趋向性的决定因素
基本信息
- 批准号:10522253
- 负责人:
- 金额:$ 83.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AgeBindingBiomassBloodBlood CirculationCandidate Disease GeneCell surfaceCellsCellular TropismCessation of lifeDiseaseErythrocytesExhibitsFamilyGenesGenetic CrossesGenetic PolymorphismGlycophorinGorilla gorillaGrowthHemoglobinopathiesHeterogeneityHumanIndividualInfectionInterventionLigandsMalariaMapsMediatingMolecularMorbidity - disease rateNatural SelectionsParasitesParasitic infectionPathogenesisPathogenicityPathway interactionsPhenotypePlasmodiumPlasmodium falciparumPopulationProcessProliferatingProteinsPublic HealthQuantitative Trait LociRecombinantsReticulocytesRoleScourgeSickle HemoglobinStagingTherapeutic InterventionTropismVariantblood groupcell agecell typedesigndisorder controlforward geneticsgenetic approachloss of functionmembermortalitypreferencepublic health interventionreceptorreverse geneticstherapy developmenttransmission processvaccine development
项目摘要
PROJECT SUMMARY
Malaria continues to be a major scourge of humanity, and is caused by infection of red blood cells (RBCs) by
the protozoan Plasmodium spp. parasites. Plasmodium falciparum can achieve high parasite biomasses in the
circulation causing severe morbidity and mortality. Blood-stage parasites have a strict cellular tropism for RBCs,
interacting with numerous molecular determinants in the RBCs for productive infection and transmission.
Parasite polymorphisms that allow parasites to propagate and persist in different types of RBCs present a major
challenge to malaria control and elimination. This includes the ability of the invasive merozoite forms to use
different receptors on RBCs, known as invasion pathways. We will leverage the power of forward genetics to
identify the molecular determinants mediating two key features of the cellular tropism of P. falciparum: RBC age
and RBC species preference. We have found that different P. falciparum strains vary significantly in these
preferences, and hypothesize that the parasite polymorphisms underlying this variation are critical to the
emergence and persistence of P. falciparum in human populations, and are key determinants of pathogenesis
and transmission. We will employ a forward genetics approach to identify polymorphisms and genes associated
with RBC age and species preference, specifically Bulk Segregant Analysis (BSA) of progeny from genetic
crosses of P. falciparum parental lines with varying invasion preferences. Reverse genetics approaches will be
used for the functional analysis of naturally occurring polymorphisms in candidate genes, both singly and in
combination. Together these studies will provide a comprehensive understanding of the molecular basis of
cellular tropism in P. falciparum parasites, focused on RBC age and species preference. In the long-term we
hope that our studies will elucidate the critical interactions required for the persistence, pathogenicity and
transmission of P. falciparum in parasite populations, to inform public health interventions and inform vaccine
development.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Manoj T Duraisingh其他文献
Hungry for control: metabolite signaling to chromatin in emPlasmodium falciparum/em
渴望控制:恶性疟原虫中代谢物向染色质的信号传导
- DOI:
10.1016/j.mib.2024.102430 - 发表时间:
2024-04-01 - 期刊:
- 影响因子:7.500
- 作者:
Ruth Lappalainen;Manish Kumar;Manoj T Duraisingh - 通讯作者:
Manoj T Duraisingh
Manoj T Duraisingh的其他文献
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{{ truncateString('Manoj T Duraisingh', 18)}}的其他基金
Linking metabolite sensing and gene expression in malaria parasites
将疟疾寄生虫的代谢物传感和基因表达联系起来
- 批准号:
10593642 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Malaria parasite determinants of host cell tropism
疟疾寄生虫宿主细胞趋向性的决定因素
- 批准号:
10646370 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Evaluating host-directed therapeutics against blood-stage malaria parasites
评估针对血期疟疾寄生虫的宿主导向疗法
- 批准号:
10665779 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Evaluating host-directed therapeutics against blood-stage malaria parasites
评估针对血期疟疾寄生虫的宿主导向疗法
- 批准号:
10528133 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Molecular basis of antimalarial drug resistance in Plasmodium vivax
间日疟原虫抗疟药物耐药性的分子基础
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10593992 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies
开发带条形码的疟原虫面板来评估广泛中和抗体
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10655645 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Comparative systems biology of apicomplexan cell division
顶端复合体细胞分裂的比较系统生物学
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10539938 - 财政年份:2022
- 资助金额:
$ 83.78万 - 项目类别:
Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies
开发带条形码的疟原虫面板来评估广泛中和抗体
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10511052 - 财政年份:2022
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Comparative systems biology of apicomplexan cell division
顶端复合体细胞分裂的比较系统生物学
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10669790 - 财政年份:2022
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