Mechanistic analysis of Toxoplasma gondii sexual development in tissue culture and mouse models
组织培养和小鼠模型中弓形虫性发育的机制分析
基本信息
- 批准号:10738256
- 负责人:
- 金额:$ 6.95万
- 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:2022-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcidsAffectAgreementAnimal ExperimentationBiological ModelsBiologyBrainCause of DeathCell Culture TechniquesCell Differentiation processCellsDataDevelopmentDiseaseEnvironmentEpigenetic ProcessEthicsEyeFamily FelidaeFatty AcidsFelis catusGenesGenetic TranscriptionGoalsGrowthHDAC3 geneHistone DeacetylaseHistone Deacetylase InhibitorHistonesHumanImmunocompromised HostIn VitroIndividualIntegration Host FactorsIntestinesKnowledgeLinoleic AcidsLipidsLiteratureMammalsMeasuresMediatingModelingModificationMolecularMusOocystsParasitesPolyunsaturated Fatty AcidsPrevalenceProductionProteinsResearchRoleSeroprevalencesSex DifferentiationSexual DevelopmentSignal PathwaySmall Interfering RNATestingTherapeuticToxoplasma gondiiToxoplasmosisUnited StatesWorkasexualautomated image analysiscell typecompanion animalexperimental studyfoodborne illnessimprovedin vivointestinal epitheliumknock-downmouse modeloverexpressionpermissivenesspreventresponsesextissue culturetransmission processvaccine development
项目摘要
Project Summary
Toxoplasma gondii is the causative agent of toxoplasmosis, a leading cause of death due to foodborne illness
that causes serious disease in immunocompromised individuals. The parasite develops asexually and
sexually, and asexual parasite development is well-studied. However, the parasite completes its sexual stage
only in the cat intestinal epithelium, presenting a significant ethical and logistical barrier to sexual stage
research. To remove the need for companion animal research and study the unknown biology of sexual stage
T. gondii, our lab developed murine and tissue culture models that support T. gondii sexual development. The
polyunsaturated fatty acid linoleic acid is a critical factor for T. gondii to complete sexual development that is
uniquely elevated in the feline intestine. The mechanisms by which linoleic acid acts on host or parasite remain
unknown. The goal of this proposal is to determine the mechanism of linoleic acid in promoting T. gondii sexual
development in cell culture and in vivo. Preliminary data from our group and others suggests that linoleic acid
acts on both host and parasite to promote a permissive environment for T. gondii sexual development. I
hypothesize that intracellular accumulation of linoleic acid activates T. gondii lipid signaling pathways to
promote sexual development. I further hypothesize that sexual development relies on activation of similar
signaling pathways in the host. In Aim 1, I will determine the mechanism of linoleic acid action on the parasite
by measuring parasite transcriptional responses to linoleic acid treatment. I will also test our new mouse model
of linoleic acid accumulation for its ability to promote efficient T. gondii sexual development in vivo. In Aim 2, I
will use automated image analysis to determine the importance of host cell type in T. gondii sexual
development. siRNA-mediated ablation of linoleic acid-responsive host factors will identify host genes that
influence sexual development. Successful completion of these Aims will better define how linoleic acid enables
growth of T. gondii sexual stages. The long-term implication of this work is a shareable model of T. gondii
sexual development that will help reduce the burden of toxoplasmosis.
项目摘要
弓形虫是弓形虫病的病原体,弓形虫病是由食源性疾病导致死亡的主要原因
导致免疫功能低下的人患上严重疾病这种寄生虫无性繁殖,
有性和无性寄生虫的发育已得到充分研究。然而,寄生虫完成了它的有性阶段,
仅存在于猫肠道上皮中,对性阶段构成了重大的道德和后勤障碍
research.为了消除伴侣动物研究的需要,研究性阶段的未知生物学
T. gondii,我们的实验室开发了小鼠和组织培养模型,支持T。弓形虫性发育的
多不饱和脂肪酸亚油酸是T.完成性发育,即
在猫科动物的肠道中含量特别高亚油酸作用于宿主或寄生虫的机制仍然存在
未知本研究旨在探讨亚油酸促进T。性弓形虫
在细胞培养和体内的发育。我们小组和其他人的初步数据表明,
作用于宿主和寄生虫,促进T.弓形虫性发育我
假设亚油酸细胞内积累激活T.弓形虫脂质信号通路
促进性发育。我进一步假设性发育依赖于类似的激活,
宿主体内的信号通路在目标1中,我将确定亚油酸对寄生虫的作用机制
通过测量寄生虫对亚油酸处理的转录反应。我也会测试我们的新老鼠模型
亚油酸积累的能力,促进有效T。体内弓形虫性发育。在目标2中,我
将使用自动图像分析来确定宿主细胞类型在T.性弓形虫
发展siRNA介导的亚油酸应答宿主因子的消除将鉴定
影响性发育。成功完成这些目标将更好地定义亚油酸如何使
T.的生长弓形虫性期这项工作的长期意义是T。弓形虫
性发育,这将有助于减轻弓形虫病的负担。
项目成果
期刊论文数量(2)
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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Nicole Marie Davis其他文献
Nicole Marie Davis的其他文献
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{{ truncateString('Nicole Marie Davis', 18)}}的其他基金
Mechanistic analysis of Toxoplasma gondii sexual development in tissue culture and mouse models
组织培养和小鼠模型中弓形虫性发育的机制分析
- 批准号:
10533513 - 财政年份:2022
- 资助金额:
$ 6.95万 - 项目类别:
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