ChBE Seminar Series: Greg Reeves, NC State University
Formation and interpretation of intercellular signals
Proper signaling between cells in both animal development and adult homeostasis is crucial for the health of the organism, while misregulated signaling results in disease states. The goal of my lab is to understand the regulation of intercellular signaling at a fundamental level to help advance knowledge of human health. As a model system, we study patterning networks in the early fruit fly embryo. This model system is extraordinarily tractable and amenable to live and fixed imaging, genetic manipulations, transgenesis, and formulation/analysis of mechanistic models.
Here we will discuss the formation and interpretation of the Dorsal/NF-κB signaling gradient, which patterns the embryo’s dorsal-ventral (DV) axis. Dorsal, a transcription factor, is retained in the cytoplasm through binding to the inhibitor, Cactus/IκB. Toll signaling on the ventral side of the embryo results in the degradation of Cactus (Cact) and the import of Dorsal into the nucleus. This results in a ventral-to-dorsal gradient in the nuclear concentration of Dorsal. The cells in the embryo respond to this gradient in a concentration-dependent fashion. In this way, a single signal through Dorsal directs the differentiation of multiple domains of sub-tissue types.
Recent measurements of the Dorsal gradient have shown that it is highly dynamic and too narrow to pattern the entire DV axis. However, our modeling work suggests that when a noise-filtering mechanism is taken into account, the Dorsal gradient may carry sufficient positional information to pattern the entire DV axis. Further model analysis on the dynamics of Dorsal gradient formation shows that the dynamics are the result of slow accumulation of total dl on the ventral side of the embryo. We present experimental and modeling results that uncover the mechanism behind this overall accumulation, and suggest this mechanism may lend robustness to the system.
Dr. Greg Reeves earned a bachelor’s degrees in Chemical Engineering and in Mathematics from University of Florida in 2002. He attended graduate school at Princeton University, where he studied computational modeling of tissue patterning in the fruit fly under the tutelage of Dr Stanislav Shvartsman. He started his postdoc at Caltech in 2007 under Dr Angela Stathopoulos and Dr Scott Fraser. He focused on quantitative imaging and image analysis of the dorsal-ventral axis of the early fly embryo. He started work at NC State University in 2010, where he has continued to study tissue patterning, using the fly embryo as his model system. His lab focuses on bringing together cutting edge live, quantitative imaging and mathematical modeling.