Data-driven Models of Cell Communication in Embryos

理解多细胞生物中控制细胞间通信的复杂信号集是一个具有挑战性的问题，需要多种工具来解决。该项目将使用发育生物学、应用数学和计算机科学的方法来揭示在发育中的果蝇胚胎中调节组织形成的复杂信号模式。本研究开发的定量、计算和可视化工具将适用于复杂三维组织或生物体中的广泛信号机制，从而为生物学提供普遍适用性的方法。此外，该项目还将为化学与生物工程、分子生物学和计算机科学系的学生以及具有应用数学和生命科学背景的博士后提供跨学科培训。受体酪氨酸激酶（RTK）激活的改变与多种发育异常有关，这激发了对发育RTK信号的定量研究。参与胚胎发生的信号系统在进化过程中高度保守，这意味着对模式生物（如果蝇）的研究将产生广泛适用的见解。早期果蝇胚胎为高通量定量实验提供了独特的机会，该项目将重点研究表皮生长因子受体（EGFR）的信号传导，EGFR是许多物种发育组织的关键调节因子。早期胚胎中的EGFR信号被准确地描述为一个导致基因表达稳定模式的时间脉冲，本项目将研究控制该脉冲定量参数及其功能的分子机制，并建立实验可测试的EGFR信号在体内的模型。该项目还将开发方法，将来自不同实验分析的信息结合起来，解决不同胚胎发育动力学的不同方面，以产生一个典型的发育轨迹。该奖项由分子和细胞生物科学部的系统和合成生物学项目以及化学、生物工程、环境和运输系统部的生物医学工程项目共同资助。

Understanding the complex set of signals that control communication between cells in a multicellular organism is a challenging problem that requires a diverse set of tools to solve. This project will use methods from developmental biology, applied mathematics and computer science to uncover the complex signaling patterns that regulate tissue formation in the developing fruit fly (Drosophila) embryo. The quantitative, computational and visualization tools to be developed in this study will be applicable to a broad range of signaling mechanisms in complex three-dimensional tissues or organisms, thereby providing methods of general applicability in biology. In addition, this project will provide interdisciplinary training for students from chemical and biological engineering, molecular biology, and computer science departments, as well as for postdoctoral fellows with applied mathematics and life sciences backgrounds. Alterations in the activation of receptor tyrosine kinases (RTKs) have been implicated in multiple developmental abnormalities, motivating quantitative studies of developmental RTK signaling. Signaling systems involved in embryogenesis have been highly conserved in evolution, which implies that studies in model organisms, such as Drosophila, yield broadly applicable insights. The early Drosophila embryo provides unique opportunities for high-throughput quantitative experiments, and this project will focus on signaling by the Epidermal Growth Factor Receptor (EGFR), a key regulator of developing tissues in many species. EGFR signaling in the early embryo is accurately described as a temporal pulse that leads to a stable pattern of gene expression, and this project will examine the molecular mechanisms controlling the quantitative parameters of this pulse and its function, as well as establishing experimentally testable models of EGFR signaling in vivo. This project will also develop methods to combine information from different experimental assays that address different aspects of developmental dynamics in different embryos to generate a stereotypical developmental trajectory.This award is funded jointly by the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences and the Biomedical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.