TRANSCRIPTOME ANALYSIS OF LEISHMANIA PANAMENSIS DEVELOPMENTAL STAGES
巴拿马利什曼原虫发育阶段的转录组分析
基本信息
- 批准号:8415833
- 负责人:
- 金额:$ 8.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AfricanAfrican TrypanosomiasisBiologyBiteCattleCentral AmericaChagas DiseaseChronicCodeCollaborationsColombiaCommunicable DiseasesCommunitiesComplementary DNACutaneousDNA Microarray ChipData SetDetectionDeteriorationDevelopmentDiseaseDomestic PigEconomic ConditionsEpidemiologyFamily memberFemaleFutureGene ExpressionGene Expression ProfileGene Expression ProfilingGenesGenetic TranslationGenomeGrantHumanImmunotherapeutic agentIn VitroInfectionInsect VectorsLeishmaniaLeishmania vianniaLeishmania viannia panamensisLeishmaniasisLesionLife Cycle StagesLivestockMalariaMastigophoraMessenger RNAMethodologyModelingMolecularMonitorMusParasitesPathogenesisPatternPharmaceutical PreparationsPhlebotominaePhylogenetic AnalysisPrevalenceProtozoaPrunella vulgarisPublic HealthRNARNA InterferenceRegimenRelative (related person)ResistanceRibosomesSamplingSignal TransductionSocial ConditionsSouth AmericaStagingSurveysSystemTechnologyTherapeuticTimeToxic effectTranscriptTranslationsTrypanosomaTrypanosomatinaVaccinesVianniaVirulencecDNA Librarydeep sequencingdisorder controlin vivointerestmacrophagenagananext generation sequencingobligate intracellular parasiteresearch studysocioeconomicstooltranscriptome sequencingtransmission processvectorwasting
项目摘要
DESCRIPTION (provided by applicant): This application focuses on trypanosomatid protozoa of the genus Leishmania, the causative agent of leishmaniasis. More than 20 species of Leishmania parasites are able to infect and cause disease in humans and their epidemiological features involve a considerable range of reservoir hosts and insect vectors, suggesting specific adaptations. Leishmaniasis is the second biggest parasitic killer following malaria, with a significant impact on deterioration of social and economic conditions. There is no vaccine available and current therapeutic regimens have serious limitations. The Leishmania (Viannia) subgenus represents a distinct phylogenetic and evolutionary group of Leishmania. Despite the prevalence of these parasites in Central and South America and their association with cutaneous and mucocutaneous disease, their mechanisms of virulence and pathogenesis have not been extensively studied. The Leishmania life cycle entails two morphologically distinct forms: transmission to the vertebrate host is initiated by flagellated metacyclic promastigotes via the bite of an infected female sandfly vector. In the mammalian host, Leishmania are obligate intracellular parasites that replicate within late endosomal/lysosomal compartments of macrophages and may be persistent for months or years. This proposal builds on the availability of a robust murine model for L. (V.) panamensis chronic infection, as well as promastigote and infectious axenic amastigote in vitro cultures. We propose to study differentiation at the molecular level by monitoring the transcriptional landscape using deep-sequencing technologies (RNA-Seq) and examining translation features of mRNA by "ribosome profiling". Traditionally, DNA microarrays were used to survey global patterns and changes in gene expression. Recent pioneering experiments have introduced RNA-Seq, a methodology employing next generation sequencing, i.e. massive parallel sequencing of cDNA. We will also explore potential translation regulatory mechanism(s) by implementing the newly-established "ribosome profiling" methodology, which correlates ribosome occupancy on mRNA with relative mRNA translation efficiencies. The proposed studies will further our understanding of L. (V.) panamensis biology, enhance our understanding of the genome coding capacity of the subgenus Viannia, contribute to determine the possible impact of translational control in Leishmania and have the potential to identify genes important for macrophage infection. The identified genes could be of interest as potential immunotherapeutic and pharmacological targets for treatment and disease control.
描述(由申请人提供):本申请关注利什曼原虫属的锥虫原虫,利什曼病的病原体。超过20种利什曼原虫能够感染人类并引起疾病,其流行病学特征涉及相当大范围的储库宿主和昆虫载体,表明特定的适应性。利什曼病是继疟疾之后的第二大寄生虫杀手,对社会和经济状况的恶化产生重大影响。没有可用的疫苗,目前的治疗方案有严重的局限性。利什曼原虫(Viannia)亚属代表利什曼原虫的一个独特的系统发育和进化组。尽管这些寄生虫在中美洲和南美洲的流行及其与皮肤和粘膜皮肤疾病的关系,其毒力和发病机制尚未得到广泛研究。利什曼原虫的生命周期需要两种形态上不同的形式:通过感染雌性白蛉媒介的叮咬,由有鞭毛的后环前鞭毛体启动向脊椎动物宿主的传播。在哺乳动物宿主中,利什曼原虫是专性细胞内寄生虫,在巨噬细胞的晚期内体/溶酶体隔室内复制,并且可能持续数月或数年。这一建议建立在一个强大的鼠模型的可用性L。(五)Panamensis慢性感染,以及前鞭毛体和感染性无鞭毛体体外培养。我们建议通过使用深度测序技术(RNA-Seq)监测转录景观并通过“核糖体分析”检查mRNA的翻译特征来研究分子水平上的分化。传统上,DNA微阵列用于调查基因表达的全球模式和变化。最近的开创性实验已经引入了RNA-Seq,这是一种采用下一代测序的方法,即cDNA的大规模平行测序。我们还将通过实施新建立的“核糖体分析”方法来探索潜在的翻译调控机制,该方法将核糖体在mRNA上的占据与相对mRNA翻译效率相关联。 这些研究将进一步加深我们对L.(五)Panamensis生物学,增强我们对Viannia亚属基因组编码能力的理解,有助于确定利什曼原虫翻译控制的可能影响,并有可能鉴定对巨噬细胞感染重要的基因。所鉴定的基因可能作为潜在的免疫学和药理学靶点用于治疗和疾病控制。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Diane McMahon Pratt其他文献
Diane McMahon Pratt的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Diane McMahon Pratt', 18)}}的其他基金
TRANSCRIPTOME ANALYSIS OF LEISHMANIA PANAMENSIS DEVELOPMENTAL STAGES
巴拿马利什曼原虫发育阶段的转录组分析
- 批准号:
8242959 - 财政年份:2012
- 资助金额:
$ 8.31万 - 项目类别:
A nanoparticle-based vaccine against leishmaniasis
基于纳米颗粒的利什曼病疫苗
- 批准号:
8318569 - 财政年份:2011
- 资助金额:
$ 8.31万 - 项目类别:
A nanoparticle-based vaccine against leishmaniasis
基于纳米颗粒的利什曼病疫苗
- 批准号:
8121354 - 财政年份:2011
- 资助金额:
$ 8.31万 - 项目类别:
Integrated Functional Genomics: On the road to leishmaniasis control Dormy House
综合功能基因组学:迈向利什曼病控制之路 Dormy House
- 批准号:
7408287 - 财政年份:2007
- 资助金额:
$ 8.31万 - 项目类别:
STRUCTURAL ANALYSIS OF GLYCOLIPID ANTIGENS OF LEISHMANIA PIFANOI AMASTIGOTES
皮法诺利什曼原虫无鞭毛体糖脂抗原的结构分析
- 批准号:
7369217 - 财政年份:2006
- 资助金额:
$ 8.31万 - 项目类别:
STRUCTURAL ANALYSIS OF GLYCOLIPID ANTIGENS OF LEISHMANIA PIFANOI AMASTIGOTES
皮法诺利什曼原虫无鞭毛体糖脂抗原的结构分析
- 批准号:
7182172 - 财政年份:2005
- 资助金额:
$ 8.31万 - 项目类别:
Intervenable Host Leishmania (Viannia) Interactions
可干预宿主利什曼原虫(Viannia)相互作用
- 批准号:
7112323 - 财政年份:2005
- 资助金额:
$ 8.31万 - 项目类别:
Intervenable Host Leishmania (Viannia) Interactions
可干预宿主利什曼原虫(Viannia)相互作用
- 批准号:
7247979 - 财政年份:2005
- 资助金额:
$ 8.31万 - 项目类别:
Intervenable Host Leishmania (Viannia) Interactions
可干预宿主利什曼原虫(Viannia)相互作用
- 批准号:
6964088 - 财政年份:2005
- 资助金额:
$ 8.31万 - 项目类别:
相似海外基金
The catalytic core of the proteasome as a drug target to treat Human African Trypanosomiasis
蛋白酶体的催化核心作为治疗非洲人类锥虫病的药物靶点
- 批准号:
10511408 - 财政年份:2022
- 资助金额:
$ 8.31万 - 项目类别:
A One Health approach to investigating the ecology of East African trypanosomiasis in Malawian wildlife
调查马拉维野生动物中东非锥虫病生态学的“同一个健康”方法
- 批准号:
476178 - 财政年份:2022
- 资助金额:
$ 8.31万 - 项目类别:
Studentship Programs
The catalytic core of the proteasome as a drug target to treat Human African Trypanosomiasis
蛋白酶体的催化核心作为治疗非洲人类锥虫病的药物靶点
- 批准号:
10677879 - 财政年份:2022
- 资助金额:
$ 8.31万 - 项目类别:
Multi-target approach to rational design of novel therapeutics for human African trypanosomiasis
多目标方法合理设计非洲人类锥虫病新疗法
- 批准号:
10466942 - 财政年份:2021
- 资助金额:
$ 8.31万 - 项目类别:
Multi-target approach to rational design of novel therapeutics for human African trypanosomiasis
多目标方法合理设计非洲人类锥虫病新疗法
- 批准号:
10296873 - 财政年份:2021
- 资助金额:
$ 8.31万 - 项目类别:
Multi-target approach to rational design of novel therapeutics for human African trypanosomiasis
多目标方法合理设计非洲人类锥虫病新疗法
- 批准号:
10706306 - 财政年份:2021
- 资助金额:
$ 8.31万 - 项目类别:
Reducing and replacing the animal cost of functional genetics in African trypanosomiasis
减少和替代非洲锥虫病功能遗传学的动物成本
- 批准号:
NC/W001144/1 - 财政年份:2021
- 资助金额:
$ 8.31万 - 项目类别:
Research Grant
Development of new drug for African trypanosomiasis based on elucidation of the mechanism of antiprotozoal action by ribavirin.
基于利巴韦林抗原虫作用机制的阐明,开发治疗非洲锥虫病的新药。
- 批准号:
21K18230 - 财政年份:2021
- 资助金额:
$ 8.31万 - 项目类别:
Grant-in-Aid for Challenging Research (Pioneering)
Development of a novel control measure for African trypanosomiasis based on the blocking of lifecycle progression
基于生命周期进展阻断的非洲锥虫病新型控制措施的开发
- 批准号:
20K07467 - 财政年份:2020
- 资助金额:
$ 8.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Drug-diagnostic co-development in Tropical Medicine, combating Human African Trypanosomiasis
热带医学药物诊断联合开发,抗击非洲人类锥虫病
- 批准号:
18KK0454 - 财政年份:2019
- 资助金额:
$ 8.31万 - 项目类别:
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))