CAREER: Engineering principles within cell-cell communication networks in animal development

North Carolina State University, Raleigh NC

Investigators

Abstract

1254344 Reeves Regulation of signaling between cells is crucial in many areas of biology, including development, stem cell biology, and proper maintenance of adult tissues. In development, tissues are patterned by long range, yet highly variable signals that direct differences in gene expression at different locations. In the Principal Investigator's lab, the overarching goal is to connect engineering principles to the regulatory mechanisms that ensure reliable gene expression patterns in the face of highly variable intercellular signals. The proposed work aims to study two specific instances of engineering principles in biological regulatory mechanisms: feedback control and noise-filtering. The fruit fly Drosophila melanogaster is used as a model organism, as it strikes a balance between the complexity needed (as a multicellular organism) and ease of manipulation, with advanced genetic and transgenesis toolkits. In the early (1-3 hours old) Drosophila embryo, the dorsal-ventral axis is patterned by the transcription factor Dorsal. In previous work, it was found that Dorsal establishes robust gene expression patterns even in the face of high intrinsic noise and extrinsic variability. Negative feedback interactions with a secondary signaling pathway, the Bone Morphogenetic Protein (BMP) pathway, are hypothesized to increase the robustness of gene expression patterns with respect to variations in Dorsal signaling. Furthermore, dorsal target genes are expressed in a location far beyond the point in which a spatial gradient of a signaling molecule is expected to reliably act. Thus, the noise-filtering capabilities of gene expression in the tail of Dorsal signaling, where noise is the highest, will be investigated. Both negative feedback interactions and noise-filtering will be studied using genetic and transgenic manipulations, quantitative (live) imaging/models of gene expression outputs, quantitative real-time PCR and quantitative Western Blot. Related to the proposed experimental studies, the outreach goal is to facilitate the synergy between engineering and biology through educational materials that highlight the engineering principles found in biological systems. An enrichment module for high school students will be developed and disseminated in partnership with the Science House, an NCSU organization that oversees K-12 outreach. The goal is to train future biology majors, at the high school junior and senior level, to be comfortable with the language and viewpoint of engineering and physics. Undergraduate students in courses taught by the PI will participate as teaching assistants. At the graduate level, a special topics course that focuses on the engineering principles in tissue patterning will be broadly disseminated with the help of the NCSU Distance Education Program. These educational materials, together with the research work, will provide the perspective and research to understand and then utilize the ?natural engineering? present in biological systems.