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

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.