Intra-species diversity among L. major isolates as determinant of ZCL polymorphis
L. Major 分离株的种内多样性是 ZCL 多态性的决定因素
基本信息
- 批准号:8321822
- 负责人:
- 金额:$ 12.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至 2017-06-30
- 项目状态:已结题
- 来源:
- 关键词:BenignClinicalComplementCountryCutaneousCutaneous LeishmaniasisCytolysisDataDiseaseDisease OutcomeDisease ResistanceGene ExpressionGenesGenetic PolymorphismGenetic VariationGoalsGrowthHealedHumanImmuneImmune responseIn VitroInbred Strains MiceIndividualInfectionInfection preventionKineticsLeishmaniaLeishmania majorLesionMiddle EastMusNatural HistoryNorthern AfricaOutcomeParasitesPathogenicityPharmaceutical PreparationsPhenotypePlayPredispositionProspective StudiesProteinsProteomicsRecording of previous eventsResidual stateResistanceRiskRoleSeveritiesSeverity of illnessTestingTranscriptTunisiaVaccinesVirulenceVirulence FactorsVisceralbasecohortfollow-uphealingimprovedmacrophageprogramsprospectivetranscriptomicsvector
项目摘要
Zoonotic Cutaneous Leishmaniasis (ZCL) is a disease highly prevalent in North Africa and Middle East that
is caused by Leishmania major There is an urgent need for improved non toxic antileishmanial drugs and
for effective vaccines that could prevent infection or symptomatic disease. The TMRC proposal aims at
describing the natural history of L. major infection in Tunisia and identifying immune correlates of protection
that takes into consideration the eventual effects of intraspecies polymorphism of L major and reservoir
diversity The specific hypothesis is that genetic variation among L. major might act, in concert with the host
immune response, to determine the outcome of infection. The specific aims of project 3 are to:1)Screen
individuals with past history of ZCL, for the persistence of residual parasites in healed lesions.2) Establish a
bank of L. major isolates from the ZCL lesions that will develop during the prospective follow up of a cohort
of individuals exposed to the risk of infection. 3) Evaluate comparatively the intra-species functional
diversity of these isolates using five experimental approaches: i- Kinetics of in vitro parasite growth in culture,
ii- In vitro resistance to complement lysis, iii- In vitro infectivity to murine or human macrophages. iv-
Experimental pathogenicity in inbred mouse strains, v- Quantification of the transcripts of a set ofpre-
selected genes expressed in indicator human macrophages infected by the various isolates. 4) Select a
subset of L. major isolates on the basis of the functional tests described above and analyze their
proteomicand transcriptomic profiles to identify proteins differentially expressed among isolates.
Data on L. major diversity generated by project 3 will be correlated to the clinical and immunological base
line informations on individuals from whom the parasites were obtained (project 1 and project 2). Parasite
strains with diverse functional phenotypes may help to identify virulence factors that might play key roles in
host-parasite interactions and immune response . It will contribute to generate a holistic view on the natural
history of ZCL considering the effect of the agent and to better understand the determinants of resistance
to the disease.
人畜共患皮肤利什曼病(ZCL)是一种在北非和中东地区高度流行的疾病。
是由主要利什曼原虫引起的,迫切需要改进的无毒抗利什曼药物和
寻找可以预防感染或症状性疾病的有效疫苗。TMRC的提案旨在
描述突尼斯主要乳杆菌感染的自然历史,并确定免疫保护相关因素
这考虑到了L大熊猫和水库猪种内多态的最终影响
多样性这个具体的假设是,大斑潜蝇之间的遗传变异可能与宿主的作用一致。
免疫反应,决定感染的结局。项目3的具体目标是:1)筛选
有ZCL既往病史的个人,对于愈合的皮损中残留寄生虫的持久性。2)建立
来自ZCL皮损的主要分离株将在队列的前瞻性随访中发展
暴露于感染风险中的个人。3)比较评价种内功能
用五种实验方法研究这些菌株的多样性:I-体外培养中寄生虫生长的动力学,
II-体外对补体裂解的抵抗力,III-对小鼠或人类巨噬细胞的体外感染性。IV-
近交系小鼠的实验性致病性,一组Pre-Pre基因转录本的v-定量
被不同分离株感染的指示性人巨噬细胞中表达的选定基因。4)选择
在上述功能试验的基础上,对主要乳杆菌菌株的亚集进行了分析
蛋白质组学和转录组分谱,以确定不同分离株之间差异表达的蛋白质。
由项目3产生的主要乳杆菌多样性的数据将与临床和免疫学基础相关。
关于从其获得寄生虫的个人的在线信息(项目1和项目2)。寄生虫
具有不同功能表型的菌株可能有助于识别毒力因子,这些因子可能在
宿主与寄生虫的相互作用和免疫反应。它将有助于生成对自然的整体看法
ZCL的病史考虑药物的影响并更好地了解耐药性的决定因素
对疾病的影响。
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 }}
Dhafer Laouini其他文献
Dhafer Laouini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('Dhafer Laouini', 18)}}的其他基金
Intra-species diversity among L. major isolates as determinant of ZCL polymorphis
L. Major 分离株的种内多样性是 ZCL 多态性的决定因素
- 批准号:
7677365 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Intra-species diversity among L. major isolates as determinant of ZCL polymorphis
L. Major 分离株的种内多样性是 ZCL 多态性的决定因素
- 批准号:
7284546 - 财政年份:2007
- 资助金额:
$ 12.77万 - 项目类别:
Intra-species diversity among L. major isolates as determinant of ZCL polymorphis
L. Major 分离株的种内多样性是 ZCL 多态性的决定因素
- 批准号:
8127868 - 财政年份:
- 资助金额:
$ 12.77万 - 项目类别:
Intra-species diversity among L. major isolates as determinant of ZCL polymorphis
L. Major 分离株的种内多样性是 ZCL 多态性的决定因素
- 批准号:
7938637 - 财政年份:
- 资助金额:
$ 12.77万 - 项目类别:
相似国自然基金
Molecular Interaction Reconstruction of Rheumatoid Arthritis Therapies Using Clinical Data
- 批准号:31070748
- 批准年份:2010
- 资助金额:34.0 万元
- 项目类别:面上项目
相似海外基金
Reducing time, sample handling, and staff requirements for complement activation monitoring in clinical trials
减少临床试验中补体激活监测的时间、样品处理和人员需求
- 批准号:
9141919 - 财政年份:2016
- 资助金额:
$ 12.77万 - 项目类别:
Exhaustive analysis for clinical application of anti-complement drugs
抗补体药物临床应用详尽分析
- 批准号:
15K09502 - 财政年份:2015
- 资助金额:
$ 12.77万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Complement activation as a therapeutic target and clinical biomarker for Parkinson's disease
补体激活作为帕金森病的治疗靶点和临床生物标志物
- 批准号:
nhmrc : 1082250 - 财政年份:2015
- 资助金额:
$ 12.77万 - 项目类别:
Project Grants
The effect of genetic polymorphism in complement proteins on clinical renal transplant outcome
补体蛋白基因多态性对临床肾移植结局的影响
- 批准号:
G0701320/1 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Research Grant
Complement Genetics and Clinical Variability of Systemic Lupus Erythematosus
系统性红斑狼疮的补体遗传学和临床变异
- 批准号:
8327290 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Complement Genetics and Clinical Variability of Systemic Lupus Erythematosus
系统性红斑狼疮的补体遗传学和临床变异
- 批准号:
7906020 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Complement Genetics and Clinical Variability of Systemic Lupus Erythematosus
系统性红斑狼疮的补体遗传学和临床变异
- 批准号:
7467641 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Complement Genetics and Clinical Variability of Systemic Lupus Erythematosus
系统性红斑狼疮的补体遗传学和临床变异
- 批准号:
7680116 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Complement Genetics and Clinical Variability of Systemic Lupus Erythematosus
系统性红斑狼疮的补体遗传学和临床变异
- 批准号:
8123298 - 财政年份:2008
- 资助金额:
$ 12.77万 - 项目类别:
Clinical application of evaluation of complement protein levels in the exocrine pancreas to determine the pancreatic disease activity
评估胰腺外分泌补体蛋白水平以确定胰腺疾病活动度的临床应用
- 批准号:
09470135 - 财政年份:1997
- 资助金额:
$ 12.77万 - 项目类别:
Grant-in-Aid for Scientific Research (B)