Collaborative Research: Modeling and Computational Analysis of Cell Communication in Drosophila Ogenesis

合作研究：果蝇发育中细胞通讯的建模和计算分析

• 批准号: 0211755
• 负责人: Stanislav Shvartsman
• 金额: $ 15.59万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0211755&HistoricalAwards=false
• 关键词: Collaborative; Research; Modeling; Computational; Analysis

Muratov0211864 Shvartsman 0211755 In this collaborative project the investigators combinemechanistic modeling, computational analysis, and experimentaltechniques of developmental genetics to analyze cellcommunication networks in the development of the Drosophila egg(oogenesis). They focus on the patterning events mediated by theEpidermal Growth Factor Receptor (EGFR), during which a localizedsource of the EGFR ligand is modulated in space and time by adistributed network of autocrine loops to produce a biochemicalblueprint specifying the formation of a pair organ. Theinvestigators develop mechanistic models of EGFR signaling inDrosophila oogenesis. These models are necessary to directly testconsistency of the proposed regulatory mechanisms, to make theexperimentally verifiable predictions, and to guide the design offuture experiments. The models should explicitly account for thekey components of the EGFR system: the receptor, four of itsligands, ligand processing proteins, and intracellular signalingcascades. The nonlinear reaction-transport models of spatiallydistributed EGFR signaling networks are analyzed using acombination of numerical simulations, asymptotic techniques, andbifurcation analysis. The tests of model-based predictions relyon experimental advantages of Drosophila genetics. Signaling through the Epidermal Growth Factor Receptor EGFRis essential in a number of developmental processes acrossspecies, from fruitflies to humans, and is extensively studied atthe molecular level. The main goal of the project is to developmodeling and computational tools necessary to describereaction-transport processes in developing epithelial layers. Inthe context of Drosophila, the investigators aim to capture alarge number of phenotypic transitions in eggshell morphologythat have been observed following quantitative manipulations inthe doses of the regulatory genes. This leads to a class ofmathematical problems that are also relevant in other biologicaland physico-chemical settings. Given the highly conserved natureof EGFR systems, it is possible that the proposed analysis ofpatterning events in Drosophila oogenesis may be used tounderstand the role of EGFR in the formation of branchedepithelial structures in the development of higher organisms. Theproject has a significant educational component: it bringstogether and trains students and postdocs in biology, engineeringand mathematics.

在这个合作项目中，研究人员将发育遗传学的力学建模、计算分析和实验技术结合起来，分析果蝇卵（卵发生）发育过程中的细胞通信网络。他们专注于表皮生长因子受体（EGFR）介导的模式事件，在此过程中，EGFR配体的局部来源通过自分泌环的分布式网络在空间和时间上进行调节，以产生指定成对器官形成的生化蓝图。研究人员开发了果蝇卵发生中EGFR信号传导的机制模型。这些模型对于直接检验所提出的调控机制的一致性、做出实验可验证的预测以及指导未来实验的设计是必要的。这些模型应该明确地解释EGFR系统的关键组成部分：受体、它的四种配体、配体加工蛋白和细胞内信号级联。利用数值模拟、渐近技术和分岔分析相结合的方法，分析了空间分布的EGFR信号网络的非线性反应-输运模型。基于模型的预测测试依赖于果蝇遗传学的实验优势。从果蝇到人类，表皮生长因子受体（egfrs）的信号传导在许多跨物种的发育过程中都是必不可少的，并且在分子水平上被广泛研究。该项目的主要目标是开发必要的建模和计算工具来描述上皮层发育中的转运过程。在果蝇的背景下，研究人员的目标是捕获大量蛋壳形态的表型转变，这些转变是在调控基因剂量的定量操作后观察到的。这导致了一类数学问题，这些问题也与其他生物和物理化学环境相关。鉴于EGFR系统的高度保守性，有可能对果蝇卵发生过程中的模式事件进行分析，以理解EGFR在高等生物发育中分支上皮结构形成中的作用。该项目有一个重要的教育组成部分：它汇集并培养了生物学、工程学和数学方面的学生和博士后。