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

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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.