Regulation of protein synthesis by metabolic signals and the circadian clock

通过代谢信号和生物钟调节蛋白质合成

基本信息

批准号：
10797235
负责人：
Albrecht G. von ARNIM
金额：
$ 2.86万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
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：
2018-07-01 至 2024-06-30
项目状态：
已结题

项目摘要

Project Summary Protein synthesis is a core function of all cells and is the target of multiple signaling pathways that coordinate the translation of mRNAs into proteins in response to exogenous and internal signals. Work from this and other laboratories has highlighted that cyclical signals from the light environment, temperature, metabolic biomarkers, and the circadian clock are integrated to coordinate mRNA ribosome loading on a genome-wide scale. Central in this network is the signaling axis known as the TOR-S6 kinase pathway. It regulates the phosphorylation of several components of the cytosolic translation apparatus including one prominent target on the ribosome, the eS6 protein located at the foot of the small ribosomal subunit. The model system underlying the current project, Arabidopsis thaliana, is not only representative of higher eukaryotes because of the conservation of its TOR-S6K-eS6 signaling channel, but is also an ideal system to study the integration of various cyclical signals in a chronobiological context. The first aim of the project builds on innovative and established molecular, biochemical, and cellular assays to tackle a long-standing question, the biochemical and cellular role of eS6-phosphorylation. Plants in which phosphorylation of eS6 is abolished or otherwise disrupted display at most minor defects in their growth, development, and transcriptome. Therefore, detailed assays of translational fidelity, ribosome biogenesis, translation, and autophagy will be refined and applied to identify the biochemical and cellular scope of eS6 phosphorylation. The second aim is a collaboration with a group of versatile computational biologists under co-investigator Tian Hong. As the cell processes multiple independent circadian signals, it can be predicted theoretically that the precise mode of their integration will lead to new circuit properties including complex waveforms or even ultradian periods. The project will use bioinformatic data mining, mathematical modeling, and wet-lab experimentation to distinguish between competing hypotheses to explain how multiple cyclical signals are integrated with each other.

项目摘要蛋白质合成是所有细胞的核心函数，是坐标的多个信号通路的目标响应外源和内部信号的mRNA转化为蛋白质。从这个和其他工作实验室强调了来自光环境，温度，代谢的周期性信号生物标志物和昼夜节律的集成以协调在全基因组上的mRNA核糖体负载规模。该网络中的中心是被称为Tor-S6激酶途径的信号轴。它调节胞质翻译设备的几个成分的磷酸化，包括一个突出的靶标核糖体，ES6蛋白位于小核糖体亚基的脚下。基础模型系统当前的项目，拟南芥，不仅代表着较高的真核生物，因为其TOR-S6K-ES6信号通道的保护，但也是研究整合的理想系统在时间生物学环境中的各种周期性信号。该项目的第一个目的是建立在创新和已建立的分子，生化和细胞测定法，以解决一个长期存在的问题，即生化 ES6-磷酸化的细胞作用。消除了ES6磷酸化的植物或其他在其成长，开发和转录组中，最小缺陷的显示中有破坏的显示。因此，详细翻译保真度，核糖体生物发生，翻译和自噬的测定将被完善并应用于确定ES6磷酸化的生化和细胞范围。第二个目标是与共同投资者天洪的多功能计算生物学家小组。随着单元格的多重处理独立的昼夜信号，可以从理论上预测其集成的精确模式将导致新的电路特性，包括复杂的波形甚至超大时期。该项目将使用生物信息学数据挖掘，数学建模和湿LAB实验，以区分竞争假设可以解释如何相互整合多个周期性信号。