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

Princeton University, Princeton NJ

Investigators

Abstract

Muratov 0211864 Shvartsman 0211755 In this collaborative project the investigators combine mechanistic modeling, computational analysis, and experimental techniques of developmental genetics to analyze cell communication networks in the development of the Drosophila egg (oogenesis). They focus on the patterning events mediated by the Epidermal Growth Factor Receptor (EGFR), during which a localized source of the EGFR ligand is modulated in space and time by a distributed network of autocrine loops to produce a biochemical blueprint specifying the formation of a pair organ. The investigators develop mechanistic models of EGFR signaling in Drosophila oogenesis. These models are necessary to directly test consistency of the proposed regulatory mechanisms, to make the experimentally verifiable predictions, and to guide the design of future experiments. The models should explicitly account for the key components of the EGFR system: the receptor, four of its ligands, ligand processing proteins, and intracellular signaling cascades. The nonlinear reaction-transport models of spatially distributed EGFR signaling networks are analyzed using a combination of numerical simulations, asymptotic techniques, and bifurcation analysis. The tests of model-based predictions rely on experimental advantages of Drosophila genetics. Signaling through the Epidermal Growth Factor Receptor EGFR is essential in a number of developmental processes across species, from fruitflies to humans, and is extensively studied at the molecular level. The main goal of the project is to develop modeling and computational tools necessary to describe reaction-transport processes in developing epithelial layers. In the context of Drosophila, the investigators aim to capture a large number of phenotypic transitions in eggshell morphology that have been observed following quantitative manipulations in the doses of the regulatory genes. This leads to a class of mathematical problems that are also relevant in other biological and physico-chemical settings. Given the highly conserved nature of EGFR systems, it is possible that the proposed analysis of patterning events in Drosophila oogenesis may be used to understand the role of EGFR in the formation of branched epithelial structures in the development of higher organisms. The project has a significant educational component: it brings together and trains students and postdocs in biology, engineering and mathematics.