Math Biology Seminar: Adriana Dawes

Nematode worms of the genus Caenorhabditis rely on an egg laying structure, called the vulva, to properly expel embryos from the adult body. Development of the vulva involves six vulval precursor cells (VPCs) adopting one of three possible cell fates: primary, secondary and tertiary. The signaling pathways involved in vulval development are highly conserved across nematode worms, although data from our group shows differential responses to partial pathway disruption between C. elegans and C. briggsae. In order to investigate the pathway components that may be responsible for these species-specific differences, we have developed a biologically based mathematical model of the main signaling networks (EGF/Ras, Notch and Wnt) responsible for VPC cell fate specification. This highly complex, nonlinear model consists of 90 equations and 71 free parameters, making standard analytic techniques unfeasible. Using novel data visualizations such as heat maps and correlation diagrams, we have identified key components in the model that account for the observed species-specific responses. In particular, we find that C. elegans-like parameter sets are more sensitive to disruptions in the EGF/Ras signaling pathway than C. briggsae-like parameter sets, and that differences in the spatial distribution of Wnt signaling may be responsible for the C. briggsae robustness. Taken together, the data analysis and visualization in this project have allowed us to identify modifications in the underlying interaction network that may give rise to the experimentally observed phenotypic variability.