Genetic analysis of cercarial release in schistosomes
血吸虫尾蚴释放的遗传分析
基本信息
- 批准号:10190794
- 负责人:
- 金额:$ 50.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-03 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AfricaBiochemical PathwayBiologyBiomphalariaBrazilCRISPR/Cas technologyCandidate Disease GeneChromosome MappingComputing MethodologiesDataDrug resistanceFranceGenesGeneticGenetic CrossesGenetic TranscriptionGenetic VariationGenomeGenomicsGenotypeHelminthsHeritabilityHumanInbreedingIndividualLaboratoriesLarvaLightMapsMeasuresMediatingMetabolic PathwayMethodsMiddle EastMolecularMutationNetwork-basedOmanParasitesParentsPatternPenetrationPeriodicityPhotoperiodPopulationProtozoaQuantitative Trait LociRNA InterferenceResistanceRodentSamplingSchistosomaSchistosoma mansoniSchistosome ParasiteSignal PathwaySnailsSouth AmericaSpecificitySporocystsTimeTranscriptTransfectionTrematodaUniversitiesVariantVirulenceWaterWorkbasecandidate validationcell motilitycohortexomeexome sequencingexperimental studygenetic analysisgenetic approachgenetic architecturegenetic linkagegenetic linkage analysisgenetic manipulationgenome-wideimprovedinfected vector rodentinterestknock-downlaboratory experimentlife historymortalityneglectnoveltraittranscriptome sequencingtransmission process
项目摘要
SUMMARY
Identification of the parasite genes that influence transmission, virulence and host specificity is of central interest
for understanding host/parasite interactions. The central aim of this proposal is to identify the genetic basis of two
such traits in Schistosoma mansoni, a parasitic fluke that infects 67 million people in South America, Middle-East
and Africa. We will focus on the larval stage of the parasite lifecycle in aquatic snails. Following penetration of the
snail host, schistosome larvae reproduce clonally, castrating their snail host, and hundreds to tens of thousands of
motile cercariae larvae are released into the water where they infect humans or rodents. Two key transmission-
related traits show high levels of heritable genetic variation among parasites. First, the timing of cercarial release
from the snail varies among populations and overlaps with the water contact patterns of their vertebrate hosts. Most
S. mansoni populations that primarily infect humans shed cercariae larvae in late morning, while parasite
populations that primarily infect rodents shed cercariae in late afternoon or night. Late shedding has evolved at least
three times in S. mansoni populations. Laboratory crosses demonstrate a simple genetic basis for this trait, but the
genetic architecture of late shedding is different in the three populations where it has been documented. Second, the
number of cercariae larvae shed from the intermediate aquatic snail host varies ≥7-fold among individual
schistosome genotypes. High shedding parasites have greater potential for transmission but also castrate and kill
their intermediate snails more rapidly than low shedding parasites. Laboratory experiments demonstrate that this
trait responds rapidly to selection and is highly heritable.
Schistosome parasites are unusual among parasites of humans because the complete lifecycle can be easily
maintained in the laboratory, so genetic crosses can be staged and thousands of progeny isolated, while a complete
genome sequence and a growing molecular toolkit now allows genomic and functional characterization. In
preliminary work, we conducted genetic crosses between diurnal and nocturnal shedding parasites from Oman and
identified a region on chr.1 that determines cercarial shedding time (LOD=6.1). In Aim 1, we will exploit the
growing schistosome molecular toolkit to fine map and functionally analyze the gene(s) that determine shedding
time in the Omani cross, and we will conduct additional crosses to determine the genetic basis of this trait in other
parasite populations where late shedding is observed. In Aim 2, we will use RNAseq to examine rhythms in
expression of nocturnal and diurnal shedding parasites from Oman across the 24 hr light/dark cycle, to investigate
the metabolic pathways underlying control of cercarial release. Finally, in Aim 3, we will analyze genetic crosses
between parasites showing 7-fold differences in numbers of cercariae shed from infected snails, and then fine map
and functionally analyze the genes involved.
We have previously used genetic linkage mapping and functional analysis to identify the mutations underlying
oxamniquine resistance in S. mansoni. We anticipate that this approach will be equally powerful for identifying the
genes that underlie heritable parasite traits that are critical for transmission, host specificity and virulence in this
important human helminth parasite. Our genetic approach also provides a novel way to probe the biology of
schistosome sporocysts, a neglected stage in the schistosome lifecycle that is key to understanding transmission
from the snail to the vertebrate host.
总结
鉴定影响寄生虫传播、毒力和宿主特异性的基因是人们感兴趣的中心
来理解宿主和寄生虫之间的相互作用这项建议的主要目的是确定两种遗传基础,
曼氏血吸虫的这种特征,这种寄生吸虫感染了南美、中东和非洲的6700万人,
和非洲我们将集中在水生蜗牛寄生虫生命周期的幼虫阶段。在渗透了
蜗牛宿主,寄生虫幼虫克隆繁殖,阉割他们的蜗牛宿主,和数百至数万
活动的尾蚴幼虫被释放到水中,在那里它们感染人类或啮齿动物。两个关键的传输-
相关性状显示寄生虫之间存在高度可遗传的遗传变异。首先,尾蚴释放的时间
不同种群之间的蜗牛,并与脊椎动物宿主的水接触模式重叠。最
S.主要感染人类的曼氏线虫种群在上午晚些时候释放尾蚴幼虫,
主要感染啮齿动物的种群在下午晚些时候或晚上排出尾蚴。晚期脱落至少进化出了
在S. mansoni人口。实验室杂交证明了这种性状的简单遗传基础,但
晚脱落的遗传结构在已记录的三个种群中是不同的。二是
从中间水生螺宿主上脱落的尾蚴幼虫数个体间差异≥7倍
多基因型。高脱落寄生虫具有更大的传播潜力,但也会阉割和杀死
它们的中间蜗牛比低脱落寄生虫更快。实验室实验表明,
性状对选择反应迅速,具有高度遗传性。
血吸虫寄生虫在人类寄生虫中是不寻常的,因为完整的生命周期可以很容易地
保持在实验室中,因此可以进行遗传杂交,并分离出数千个后代,而一个完整的
基因组序列和不断增长的分子工具包现在允许基因组和功能表征。在
初步工作,我们进行了遗传杂交昼夜脱落寄生虫从阿曼和
确定了一个决定尾蚴脱落时间的区域(LOD=6.1)。在目标1中,我们将利用
不断发展的血吸虫分子工具包,用于精细绘制和功能分析决定脱落的基因
时间在阿曼交叉,我们将进行额外的杂交,以确定这种性状的遗传基础,在其他
观察到晚期脱落的寄生虫种群。在目标2中,我们将使用RNAseq检查
阿曼夜间和昼夜脱落寄生虫在24小时光/暗周期中的表达,以研究
控制尾蚴释放的代谢途径。最后,在目标3中,我们将分析遗传杂交
寄生虫之间显示7倍的差异,从受感染的蜗牛脱落的尾蚴数量,然后精细地图
并对相关基因进行功能分析。
我们以前使用遗传连锁图谱和功能分析来确定潜在的突变,
S. mansoni我们预计,这种方法将同样强大的识别
这些基因是可遗传的寄生虫特征的基础,这些特征对传播、宿主特异性和毒力至关重要,
重要人体蠕虫寄生虫。我们的遗传学方法也提供了一种新的方法来探索生物学,
血吸虫孢子囊,血吸虫生命周期中被忽视的阶段,是了解传播的关键
从蜗牛到脊椎动物宿主
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genetic Crosses and Linkage Mapping in Schistosome Parasites.
- DOI:10.1016/j.pt.2018.08.001
- 发表时间:2018-11
- 期刊:
- 影响因子:9.6
- 作者:Anderson TJC;LoVerde PT;Le Clec'h W;Chevalier FD
- 通讯作者:Chevalier FD
Prospecting for Zoonotic Pathogens by Using Targeted DNA Enrichment.
- DOI:10.3201/eid2908.221818
- 发表时间:2023-08
- 期刊:
- 影响因子:11.8
- 作者:Enabulele, Egie E.;Le Clec'h, Winka;Roberts, Emma K.;Thompson, Cody W.;McDonough, Molly M.;Ferguson, Adam W.;Bradley, Robert D.;Anderson, Timothy J. C.;Platt, Roy N.
- 通讯作者:Platt, Roy N.
Urogenital schistosomiasis in Nigeria post receipt of the largest single praziquantel donation in Africa.
- DOI:10.1016/j.actatropica.2021.105916
- 发表时间:2021-07
- 期刊:
- 影响因子:2.7
- 作者:Enabulele EE;Platt RN;Adeyemi E;Agbosua E;Aisien MSO;Ajakaye OG;Ali MU;Amaechi EC;Atalabi TE;Auta T;Awosolu OB;Dagona AG;Edo-Taiwo O;Ejikeugwu CEP;Igbeneghu C;Njom VS;Orji MN;Oyinloye FOP;Ozemoka HJ;Ugah UI;Anderson TJC
- 通讯作者:Anderson TJC
The hemolymph of Biomphalaria snail vectors of schistosomiasis supports a diverse microbiome.
- DOI:10.1111/1462-2920.15303
- 发表时间:2020-12
- 期刊:
- 影响因子:5.1
- 作者:Chevalier FD;Diaz R;McDew-White M;Anderson TJC;Le Clec'h W
- 通讯作者:Le Clec'h W
No evidence for schistosome parasite fitness trade-offs in the intermediate and definitive host.
- DOI:10.1186/s13071-023-05730-3
- 发表时间:2023-04-17
- 期刊:
- 影响因子:3.2
- 作者:
- 通讯作者:
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Tim J Anderson其他文献
Tim J Anderson的其他文献
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{{ truncateString('Tim J Anderson', 18)}}的其他基金
Genomic consequences of schistosome hybridization
血吸虫杂交的基因组后果
- 批准号:
10346459 - 财政年份:2021
- 资助金额:
$ 50.36万 - 项目类别:
Genomic consequences of schistosome hybridization
血吸虫杂交的基因组后果
- 批准号:
10678916 - 财政年份:2021
- 资助金额:
$ 50.36万 - 项目类别:
Efficient Linkage Mapping Methods for Schistosoma mansoni
曼氏血吸虫的高效连锁作图方法
- 批准号:
8386269 - 财政年份:2012
- 资助金额:
$ 50.36万 - 项目类别:
Efficient Linkage Mapping Methods for Schistosoma mansoni
曼氏血吸虫的高效连锁作图方法
- 批准号:
8500172 - 财政年份:2012
- 资助金额:
$ 50.36万 - 项目类别:
Genetic Analysis of Host Specificity in Schistosoma mansoni
曼氏血吸虫宿主特异性的遗传分析
- 批准号:
8401136 - 财政年份:2011
- 资助金额:
$ 50.36万 - 项目类别:
Identification of Novel Plant-derived Antimalarial Compounds
新型植物源抗疟化合物的鉴定
- 批准号:
8298963 - 财政年份:2011
- 资助金额:
$ 50.36万 - 项目类别:
Genetic Analysis of Host Specificity in Schistosoma mansoni
曼氏血吸虫宿主特异性的遗传分析
- 批准号:
8586839 - 财政年份:2011
- 资助金额:
$ 50.36万 - 项目类别:
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