Data-driven Models of Cell Communication in Embryos

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Understanding the complex set of signals that control communication between cells in a multicellular organism is a challenging problem that requires a diverse set of tools to solve. This project will use methods from developmental biology, applied mathematics and computer science to uncover the complex signaling patterns that regulate tissue formation in the developing fruit fly (Drosophila) embryo. The quantitative, computational and visualization tools to be developed in this study will be applicable to a broad range of signaling mechanisms in complex three-dimensional tissues or organisms, thereby providing methods of general applicability in biology. In addition, this project will provide interdisciplinary training for students from chemical and biological engineering, molecular biology, and computer science departments, as well as for postdoctoral fellows with applied mathematics and life sciences backgrounds. Alterations in the activation of receptor tyrosine kinases (RTKs) have been implicated in multiple developmental abnormalities, motivating quantitative studies of developmental RTK signaling. Signaling systems involved in embryogenesis have been highly conserved in evolution, which implies that studies in model organisms, such as Drosophila, yield broadly applicable insights. The early Drosophila embryo provides unique opportunities for high-throughput quantitative experiments, and this project will focus on signaling by the Epidermal Growth Factor Receptor (EGFR), a key regulator of developing tissues in many species. EGFR signaling in the early embryo is accurately described as a temporal pulse that leads to a stable pattern of gene expression, and this project will examine the molecular mechanisms controlling the quantitative parameters of this pulse and its function, as well as establishing experimentally testable models of EGFR signaling in vivo. This project will also develop methods to combine information from different experimental assays that address different aspects of developmental dynamics in different embryos to generate a stereotypical developmental trajectory.This award is funded jointly by the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences and the Biomedical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.