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

Muratov0211864 Shvartsman 0211755在这个合作项目中，研究人员结合了发育遗传学的机械建模、计算分析和实验技术，分析了果蝇卵(卵子发生)发育过程中的细胞通讯网络。他们关注的是由表皮生长因子受体(EGFR)介导的图案化事件，在此期间，EGFR配体的局部来源在空间和时间上受到分布的自分泌环网络的调节，以产生指定一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信号转导的机制模型。这些模型对于直接测试所提出的调控机制的一致性、做出可通过实验验证的预测以及指导未来实验的设计是必要的。这些模型应该清楚地说明EGFR系统的关键组成部分：受体、其四种配体、配体处理蛋白和细胞内信号级联。采用数值模拟、渐近技术和分叉分析相结合的方法，分析了空间分布的EGFR信号网络的非线性反应-传输模型。基于模型的预测检验依赖于果蝇遗传学的实验优势。通过表皮生长因子受体的信号转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，并在分子水平上进行了广泛的研究。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作用-运输过程。在果蝇的背景下，研究人员的目标是捕捉在调节基因剂量的定量操作后观察到的蛋壳形态中的大量表型转变。这导致了一类在其他生物和物理化学环境中也相关的数学问题。鉴于EGFR系统的高度保守性，所提出的对果蝇卵子发生中的模式事件的分析可能被用来理解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：它将学生和博士后集中在一起，培训生物、工程和数学方面的博士后。

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.