A COMPREHENSIVE RESOURCE FOR HIGH-THROUGHPUT PROFILING OF WORM AND ZEBRAFISH METABOLOMES
A COMPREHENSIVE RESOURCE FOR HIGH-THROUGHPUT PROFILING OF WORM AND ZEBRAFISH METABOLOMES
批准号:
10168257
负责人:
Gary J Patti
金额:
$75.33万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-04 至 2022-06-30
关键词:
2019-nCoVAddressAnimal ModelAnimalsAwardBiological ModelsCOVID-19COVID-19 pandemicCaenorhabditis elegansClinical TrialsComplexDataData SetDependenceDiseaseDisease modelDoseDrug ScreeningDrug TargetingExposure toFunctional disorderFutureGlycolysisGoalsHealthHumanHydroxychloroquineInfectionKnowledgeMapsMetabolicMetabolic PathwayMetabolic dysfunctionMetabolismModelingOrgan failureParentsPathogenesisPathologyPathway interactionsPatientsPharmaceutical PreparationsPharmacologyPositioning AttributeProblem SolvingProcessRecoveryReportingResearchResearch PersonnelResourcesRespiratory distressSamplingTechnologyTestingTherapeuticTimeToxic effectTranslatingViralViral PathogenesisVirusVirus ReplicationWorkZebrafishautomated analysiscytokine release syndromedefined contributiondesignexperimental studyfatty acid oxidationglobal healthhigh throughput screeninghuman diseasehuman subjectimprovedinsightmetabolic abnormality assessmentmetabolic profilemetabolomemetabolomicsmetabolomics resourcenew therapeutic targetnovel therapeuticsresponsesmall molecule
中文摘要
项目总结
英文摘要
Project Summary
Coronavirus disease 2019, also known as COVID-19, has created an unprecedented global health crisis.
Thus far, the only strategy to minimize spread of the virus has been physical distancing. Unfortunately, these
efforts are negatively impacting the psychiatric health of the nation and devastating our economy. It is therefore
imperative that a treatment for COVID-19 be developed expeditiously.
Worms (Caenorhabditis elegans) and zebrafish (Danio rerio) are premier model organisms that have
historically provided profound insight into a number of human diseases. At this time, however, the application
of worms and zebrafish to COVID-19 has been severely limited. Currently, the major issue is that there are no
reported models in these animals to capture the complex pathophysiology of COVID-19. The overarching
objective of the current proposal is to create a resource that will help bridge this gap. Specifically, we aim to
facilitate the application of metabolomics to COVID-19 related studies in worms and zebrafish.
The basis of our work will be metabolomic analysis of human patients with COVID-19. In addition to
comparing patients with mild and severe disease, samples from an infected patient will be compared to
samples from the same patient after recovery. Together, we expect these experiments to provide a
comprehensive picture of metabolic pathways that are altered during COVID-19 pathology.
We will then map the metabolic dysfunction we uncover in patients to the worm and zebrafish metabolomes
by using technologies that we have developed in the parent award. The result will be a resource delineating a
comprehensive set of reference COVID-19 pathways in worms and in zebrafish. This will empower the use of
worms and zebrafish to answer important COVID-19 questions, two examples of which we propose to pursue
here. Our first question is: what is the mode of action of small-molecule drugs in clinical trials to treat COVID-
19 patients (e.g., hydroxychloroquine)? We will perform dose-response metabolomics on zebrafish exposed to
20 small-molecule drugs currently in clinical trials to treat COVID-19. A comparison of each drug’s target to
reference COVID-19 pathways will provide insight into mode of action, off-target toxicity, and potentially assist
in the improved design of new drugs. Our second question is: which disease processes contribute to COVID-
19 pathology? We will perform metabolomics on zebrafish models of cytokine storm, respiratory distress, and
organ failure. Comparing metabolic changes from each of these models to reference COVID-19 pathways will
improve our understanding of which disease processes contribute to COVID-19 pathology.
We note that the drugs and disease processes that we propose to evaluate here are largely incomplete,
with many additional drugs and C. elegans disease models available to test. These opportunities, and many
others, represent exciting future applications of our resource to advance our understanding of COVID-19
through the use of model animals.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Washington University Omics Production Center
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批准号:10743660
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项目类别:
-
资助金额:$311.0万
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财政年份:2023
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负责人:Gary J Patti
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依托单位:
A COMPREHENSIVE RESOURCE FOR HIGH-THROUGHPUT PROFILING OF WORM AND ZEBRAFISH METABOLOMES
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批准号:10206284
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项目类别:
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资助金额:$73.68万
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财政年份:2018
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负责人:Gary J Patti
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依托单位:
A Comprehensive Platform for High-Throughput Profiling of the Human Reference Metabolome
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批准号:10237905
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项目类别:
-
资助金额:$44.87万
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财政年份:2018
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负责人:Gary J Patti
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依托单位:
Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
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批准号:9977200
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项目类别:
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资助金额:$74.06万
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财政年份:2017
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负责人:Gary J Patti
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依托单位:
Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
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批准号:10228022
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项目类别:
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资助金额:$72.47万
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财政年份:2017
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负责人:Gary J Patti
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依托单位:
Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
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批准号:10673074
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项目类别:
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资助金额:$68.25万
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财政年份:2017
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负责人:Gary J Patti
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依托单位:
Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
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批准号:10455670
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项目类别:
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资助金额:$70.4万
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财政年份:2017
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负责人:Gary J Patti
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依托单位:
Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
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批准号:9754149
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项目类别:
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资助金额:$76.11万
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财政年份:2017
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负责人:Gary J Patti
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依托单位:
CELL-SPECIFIC ISOTOPE LABELING TO TRACK INTERCELLULAR METABOLITE EXCHANGE IN CANCER
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批准号:8928878
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项目类别:
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资助金额:$19.9万
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财政年份:2015
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负责人:Gary J Patti
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依托单位:
DEVELOPING THE UNTARGETED METABOLOMIC WORKFLOW FOR HIGH-THROUGHPUT ANALYSES
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批准号:8687653
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项目类别:
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资助金额:$36.86万
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财政年份:2012
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负责人:Gary J Patti
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依托单位:
DEVELOPING THE UNTARGETED METABOLOMIC WORKFLOW FOR HIGH-THROUGHPUT ANALYSES
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批准号:8545852
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项目类别:
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资助金额:$35.75万
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财政年份:2012
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负责人:Gary J Patti
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依托单位:
DEVELOPING THE UNTARGETED METABOLOMIC WORKFLOW FOR HIGH-THROUGHPUT ANALYSES
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批准号:8416083
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项目类别:
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资助金额:$36.86万
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财政年份:2012
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负责人:Gary J Patti
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依托单位:
DEVELOPING THE UNTARGETED METABOLOMIC WORKFLOW FOR HIGH-THROUGHPUT ANALYSES
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批准号:8857439
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项目类别:
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资助金额:$36.86万
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财政年份:2012
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负责人:Gary J Patti
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依托单位:
Clinical Science Research Core
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批准号:10617229
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项目类别:
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资助金额:$33.28万
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财政年份:1999
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负责人:Gary J Patti
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依托单位:
海外基金