Mapping protein communication between organs in homeostasis and disease

绘制稳态和疾病中器官之间的蛋白质通讯图

基本信息

批准号：
10197922
负责人：
STEVEN A CARR
金额：
$ 164.21万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-25 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10197922
关键词：
Address Adipose tissue Affinity B Cell Proliferation Basic Science Biomedical Research Biotin Blood Blood Pressure Blood specimen Brain Communication Communities Complex Destinations Development Disease Disputes Distant Drosophila genus Engineering Equilibrium Escherichia coli Exercise Family member Fatty acid glycerol esters Future GDF11 gene Genetic Goals Gonadal structure Grant Growth Homeostasis Human Hypertension Institutes Interleukin-6 Ketone Bodies Kidney Label Leptin Ligase Liver Mammals Mass Spectrum Analysis Mediator of activation protein Metabolic Metabolism Methods Modeling Mus Muscle Myocardial Contraction Nature Nutrient Obesity Organ Organism Peripheral Physiological Problem Solving Process Proteins Proteomics Refuse Disposal Reporting Reproducibility Reproduction Signal Pathway Signal Transduction Skeletal Muscle Source Technology Therapeutic Therapeutic Intervention Tissues Transforming Growth Factor beta United States National Institutes of Health Water adipokines adiponectin base biomedical resource body system brain behavior experimental study in vivo innovation insight novel novel strategies overexpression peptide hormone protein transport salt balance sugar therapeutic candidate tool uptake

Address Adipose tissue Affinity B Cell Proliferation Basic Science Biomedical Research Biotin Blood Blood Pressure Blood specimen Brain Communication Communities Complex Destinations Development Disease Disputes Distant Drosophila genus Engineering Equilibrium Escherichia coli Exercise Family member Fatty acid glycerol esters Future GDF11 gene Genetic Goals Gonadal structure Grant Growth Homeostasis Human Hypertension Institutes Interleukin-6 Ketone Bodies Kidney Label Leptin Ligase Liver Mammals Mass Spectrum Analysis Mediator of activation protein Metabolic Metabolism Methods Modeling Mus Muscle Myocardial Contraction Nature Nutrient Obesity Organ Organism Peripheral Physiological Problem Solving Process Proteins Proteomics Refuse Disposal Reporting Reproducibility Reproduction Signal Pathway Signal Transduction Skeletal Muscle Source Technology Therapeutic Therapeutic Intervention Tissues Transforming Growth Factor beta United States National Institutes of Health Water adipokines adiponectin base biomedical resource body system brain behavior experimental study in vivo innovation insight novel novel strategies overexpression peptide hormone protein transport salt balance sugar therapeutic candidate tool uptake

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项目摘要

PROJECT SUMMARY Our interdisciplinary team proposes to develop and apply a novel method to systematically identify proteins involved in inter-organ communication. While a number of hormone peptides have been identified in mammals, many physiologically important factors involved in energy homeostasis, water-salt balance, pH, and blood pressure remain to be identified. As existing methods of identifying secreted factors from the blood using mass spectrometry (MS) have serious limitations, we will use an engineered promiscuous biotin protein ligase to biotinylate secreted proteins in a specific organ, and then identify biotinylated proteins in distant target organs through affinity enrichment followed by quantitative MS. These experiments will be performed in two organisms, Drosophila and the mouse. Drosophila facilitates the rapid development and optimization of the basic research strategy, generating evolutionary insight into conserved factors in organ communication. The mouse provides a more direct discovery model for biomedically-relevant, inter-organ regulatory communication in humans. In addition to identifying factors involved in organ communication, both in normal and disease conditions, our findings will provide fundamental insight into novel proteins that could be used in the future as therapeutics. Given our goal to broadly interconnect organ systems, the project is relevant to most NIH Institutes.

项目摘要我们的跨学科团队建议开发和应用一种新颖的方法来系统地识别蛋白质参与器官间交流。虽然在哺乳动物中鉴定出许多激素肽，但能量稳态，水盐平衡，pH和血液中涉及的许多生理上重要的因素压力仍有待确定。作为现有的使用质量从血液中识别分泌因素的方法光谱法（MS）有严重的局限性，我们将使用工程化的混杂生物素蛋白连接酶在特定器官中的生物素基因分泌蛋白，然后鉴定远处靶器官中的生物素化蛋白通过亲和力富集，然后进行定量MS。这些实验将在两次中进行生物，果蝇和小鼠。果蝇促进了快速发展和优化基础研究策略，产生对器官通信中保守因素的进化洞察力。这鼠标提供了更直接的发现模型，用于与生物医学相关的，器官间的调节通信在人类中。除了确定正常和疾病中器官通信涉及的因素条件，我们的发现将提供对新型蛋白质的基本见解，这些蛋白质将来可以用作疗法。鉴于我们的目标是广泛互连器官系统，该项目与大多数NIH有关机构。