Date of this Version
Bird, S. 2021. Boolean Network Model Reveals Different Dynamics of Far1 and Hog1 in Inhibiting Budding Yeast Cell with Stress. Undergraduate Honors Thesis. University of Nebraska-Lincoln.
Mitogen-activated protein kinase (MAPK) Hog1 and cyclin-dependent kinase inhibitor (CKI) Far1 are both well-known for negatively regulating cell cycle progression in Saccharomyces cerevisiae. Existing data suggests that Hog1 arrests or delays cell cycle phase G1 and also delays cell cycle phase G2 by indirectly inhibiting and downregulating the transcription of cyclins in response to osmotic stress. Meanwhile, Far1 arrests or delays G1 by directly inhibiting G1 cyclin complexes in response to mating pheromones. Although the mechanisms of Hog1 and Far1 have been well studied, a direct comparison of the dynamics between the two mechanisms of arrest has not yet been characterized to the best of our knowledge. Validated models of the budding yeast cell cycle regulatory network were inputted into the Boolean modeling-based Cell Collective platform, and simulation graphs of these models were used to elucidate and compare the impacts of Hog1 and Far1. We show that Far1 is extremely effective at arresting the cell cycle during very specific time points, whereas the effects of Hog1 occur with generally lesser influence over a wider range of time points and cell cycle phases. Our results are consistent with the known functions of both cell cycle inhibitors: Hog1 as an acute osmotic stress response and Far1 as a mediator of the less immediate mating process.