Ecology of Cystic Fibrosis

囊性纤维化的生态学

基本信息

  • 批准号:
    8327914
  • 负责人:
  • 金额:
    $ 2.51万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-12-01 至 2014-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cystic Fibrosis (CF) is a genetic disease that dramatically decreases life expectancy and quality. The disease is characterized by polymicrobial infections, which lead to lung remodeling and airway mucus plugging. CF patients experience intermittent exacerbations that cause airway scarring and eventually result in seriously impaired respiration. Despite aggressive therapy, most CF patients will die from respiratory failure caused by the chronic lung infections. Standard clinical microbiological studies and antibiotic susceptibility testing have severe limitations in predicting medical outcomes from specific therapies. This is due in part because the dynamics of microbes and their viral predators (phage) are essentially unknown in the CF lung. The goal of this study is to use metagenomics and microscopy to characterize these two communities and determine how they change in response to perturbations such as disease severity, antibiotic treatments, and chemical treatments designed to break up the mucus plugs. The metagenomic data will be used to determine how the types and metabolic functions of both the viral and microbial communities change. Microbial growth rates and phage-mediated death will also be measured. To better understand the spatial dynamics of the microbial and viral communities, we will also be dissecting lungs of CF patients. Viral and microbial metagenomes from individual lobes will be sequenced. To determine where specific species of microbes reside in the mucus plugs, fluorescent in situ hybridization with 16S rDNA probes will used on tissue samples. Together these data sets will be used to parameterize three complementary ecological models of the CF lung. Then these models will be used as in silico tests of alternative treatment regimes (e.g., adjust timing of antibiotic administration). When completed, we will have generated an unprecedented view of the viral and microbial communities in CF and how they respond to treatments. With the models, we will be able to better understand the dynamics of these communities and test alternative treatment regimes to prolong and improve the lives of CF patients.
描述(申请人提供):囊性纤维化(CF)是一种遗传性疾病,显著降低预期寿命和质量。这种疾病的特点是多菌感染,导致肺重塑和呼吸道粘液堵塞。Cf患者会出现间歇性加重,导致呼吸道结疤,最终导致呼吸严重受损。尽管进行了积极的治疗,但大多数CF患者仍会死于慢性肺部感染引起的呼吸衰竭。标准的临床微生物学研究和抗生素敏感性测试在预测特定治疗的医疗结果方面存在严重限制。这在一定程度上是因为微生物及其病毒捕食者(噬菌体)的动态在CF肺中基本上是未知的。这项研究的目标是使用元基因组学和显微镜来描述这两个群落的特征,并确定它们如何随着疾病严重性、抗生素治疗和旨在打破粘液堵塞的化学治疗等扰动而变化。元基因组数据将用于确定病毒和微生物群落的类型和代谢功能如何变化。微生物生长率和噬菌体介导的死亡也将被测量。为了更好地了解微生物和病毒群落的空间动态,我们还将解剖CF患者的肺。来自单个肺叶的病毒和微生物元基因组将被测序。为了确定特定种类的微生物在粘液塞中的位置,将在组织样本上使用16S rDNA探针的荧光原位杂交。这些数据集一起将被用来对三个互补的CF肺生态模型进行参数化。然后,这些模型将被用于替代治疗方案的计算机测试(例如,调整抗生素给药的时间)。完成后,我们将对CF中的病毒和微生物群落以及它们对治疗的反应产生前所未有的看法。有了这些模型,我们将能够更好地了解这些社区的动态,并测试替代治疗方案,以延长和改善CF患者的生命。

项目成果

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FOREST L ROHWER其他文献

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{{ truncateString('FOREST L ROHWER', 18)}}的其他基金

Fecal Phage: Exposing Unknown in the Dark Matter of the Human Gut
粪便噬菌体:暴露人类肠道暗物质中的未知物质
  • 批准号:
    8532486
  • 财政年份:
    2012
  • 资助金额:
    $ 2.51万
  • 项目类别:
Hydra as an Antiviral Innate Immunity Model System
Hydra 作为抗病毒先天免疫模型系统
  • 批准号:
    8233283
  • 财政年份:
    2011
  • 资助金额:
    $ 2.51万
  • 项目类别:
Hydra as an Antiviral Innate Immunity Model System
Hydra 作为抗病毒先天免疫模型系统
  • 批准号:
    8096864
  • 财政年份:
    2011
  • 资助金额:
    $ 2.51万
  • 项目类别:
Ecology of Cystic Fibrosis
囊性纤维化的生态学
  • 批准号:
    8390507
  • 财政年份:
    2010
  • 资助金额:
    $ 2.51万
  • 项目类别:
Ecology of Cystic Fibrosis
囊性纤维化的生态学
  • 批准号:
    8197889
  • 财政年份:
    2010
  • 资助金额:
    $ 2.51万
  • 项目类别:
Ecology of Cystic Fibrosis
囊性纤维化的生态学
  • 批准号:
    8587487
  • 财政年份:
    2010
  • 资助金额:
    $ 2.51万
  • 项目类别:
Ecology of Cystic Fibrosis: Administrative Supplement
囊性纤维化的生态学:行政补充
  • 批准号:
    8637669
  • 财政年份:
    2010
  • 资助金额:
    $ 2.51万
  • 项目类别:
Ecology of Cystic Fibrosis
囊性纤维化的生态学
  • 批准号:
    8015189
  • 财政年份:
    2010
  • 资助金额:
    $ 2.51万
  • 项目类别:

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