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: 0211864
• 负责人: Cyrill Muratov
• 金额: --
• 依托单位: New Jersey Institute of Technology
• 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=0211864&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.

Shvartsman 0211755 在这个合作项目中，研究人员结合了发育遗传学的机制建模、计算分析和实验技术来分析果蝇卵子发育（卵子发生）中的细胞通讯网络。 他们专注于表皮生长因子受体（EGFR）介导的模式化事件，在此期间，EGFR配体的局部来源在空间和时间上受到自分泌环的分布式网络的调节，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子发生中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都是必要的。 这些模型应该明确地解释EGFR系统的关键组成部分：受体、四种亚型、配体加工蛋白和细胞内信号级联。 结合数值模拟、渐近技术和分岔分析，对空间分布EGFR信号网络的非线性反应-传递模型进行了分析。 基于模型的预测的测试依赖于果蝇遗传学的实验优势。 通过表皮生长因子受体EGFR的信号传导在从果蝇到人类的许多物种的发育过程中是必不可少的，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，以描述发育中的上皮层的反应-运输过程。 在果蝇的研究中，研究者的目标是捕捉大量的蛋壳形态的表型转变，这些转变是在调控基因剂量下进行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有关。 鉴于EGFR系统的高度保守性，我们提出的果蝇卵子发生中的模式化事件分析可能用于理解EGFR在高等生物体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：它将学生和博士后聚集在一起，并在生物学，工程学和数学方面进行培训。