MathBio Seminar

Speakers: Mikhal Banwarth-Kuhn and Jordan Collignon
Title: Quantifying the biophysical impact of budding division in yeast
Absract: Prion proteins are most commonly associated with fatal neurodegenerative diseases in mammals, but they are also responsible for a number of harmless heritable phenotypes in yeast. Under certain experimental conditions, changes in protein aggregation dynamics between neighboring cells in yeast colonies result in sectors corresponding to loss of the prion phenotype. The resulting phenotypic organization provides a rich data set that can be used to uncover relationships between molecular processes, individual cell behaviors and phenotypic transitions at the colony level. In this talk, we first develop and analyze a center-based model to study the impact of budding cell division and nutrient limitation on yeast colony organization. We find that while budding division does not impact large-scale properties of the colony (such as shape and size), local spatial organization of cells with respect to spatial layout of mother-daughter cell pairs and connectivity of subcolonies is greatly impacted. In addition, we find that nutrient limitation further promotes local spatial organization of cells and changes global colony organization by driving variation in subcolony sizes. We next present our recent success using the Hough Transform to analyze experimental images of yeast colonies as well as describe our current progress toward developing a convolutional neural-network approach for rigorously quantifying the shape, size and structure between different sectoring phenotypes in experiments. Our combined modeling and informatics approach offers the opportunity to make more meaningful comparisons between experimental data and model output in order to infer, predict, and eliminate hypotheses on the mechanisms driving experimentally observed sectored yeast colony phenotypes.