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：
10434875
负责人：
STEVEN A CARR
金额：
$ 163.86万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434875
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

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.

项目概要我们的跨学科团队建议开发并应用一种新方法来系统地识别蛋白质参与器官间的通讯。虽然在哺乳动物中已鉴定出多种激素肽，许多与能量稳态、水盐平衡、pH 值和血液有关的重要生理因素压力仍有待确定。作为使用质量识别血液中分泌因子的现有方法光谱分析 (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来生物素化特定器官中的分泌蛋白，然后识别远处目标器官中的生物素化蛋白通过亲和力富集，然后进行定量 MS。这些实验将分两次进行有机体、果蝇和小鼠。果蝇促进了系统的快速发展和优化基础研究策略，对器官通讯中的保守因素产生进化洞察。这小鼠为生物医学相关的器官间调节通信提供了更直接的发现模型在人类中。除了确定正常和疾病状态下参与器官通讯的因素之外在条件下，我们的研究结果将为新蛋白质提供基本见解，这些蛋白质可以在未来用作疗法。鉴于我们的目标是广泛互连器官系统，该项目与大多数 NIH 相关研究所。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Protein phosphatase 1 regulates core PCP signaling.

蛋白磷酸酶 1 调节核心 PCP 信号传导。

DOI：
发表时间：
2023-12-06
期刊：
影响因子：
7.7
作者：
Song, Song;Cho, Bomsoo;Weiner, Alexis T;Nissen, Silas Boye;Ojeda Naharros, Irene;Sanchez Bosch, Pablo;Suyama, Kaye;Hu, Yanhui;He, Li;Svinkina, Tanya;Udeshi, Namrata D;Carr, Steven A;Perrimon, Norbert;Axelrod, Jeffrey D
通讯作者：
Axelrod, Jeffrey D

Protein phosphatase 1 regulates core PCP signaling.

蛋白磷酸酶 1 调节核心 PCP 信号传导。

DOI：
发表时间：
2023-09-13
期刊：
影响因子：
0
作者：
Song, Song;Cho, Bomsoo;Weiner, Alexis T;Nissen, Silas Boye;Naharros, Irene Ojeda;Bosch, Pablo Sanchez;Suyama, Kaye;Hu, Yanhui;He, Li;Svinkina, Tanya;Udeshi, Namrata D;Carr, Steven A;Perrimon, Norbert;Axelrod, Jeffrey D
通讯作者：
Axelrod, Jeffrey D

Split-TurboID enables contact-dependent proximity labeling in cells.

Split-TurboID 可在细胞中实现接触依赖性邻近标记。

DOI：
发表时间：
2020-06-02
期刊：
影响因子：
11.1
作者：
Cho, Kelvin F;Branon, Tess C;Rajeev, Sanjana;Svinkina, Tanya;Udeshi, Namrata D;Thoudam, Themis;Kwak, Chulhwan;Rhee, Hyun;Lee, In;Carr, Steven A;Ting, Alice Y
通讯作者：
Ting, Alice Y

Proximity labeling in mammalian cells with TurboID and split-TurboID.

使用 TurboID 和 split-TurboID 在哺乳动物细胞中进行邻近标记。