Mathematical modeling of the Candida albicans yeast to hyphal transition reveals key decision points and predicts control strategies
Phenotypic plasticity between two morphological phenotypes, yeast and hyphae, is a key mechanism by which Candida albicans can thrive in many microenvironments and cause disease in a host. Understanding the decision points and key driver genes controlling this important transition and how these genes respond to different environmental signals is critical to understanding how C. albicans causes infections. My group built a mathematical model of the C. albicans yeast to hyphal transition, integrating multiple environmental factors and regulatory mechanisms. We validated the model by a systematic comparison to prior experiments. The discrepancies motivated alternative hypotheses that are testable by follow-up experiments. Analysis of this model (by methods initiated by my group) revealed two time-constrained windows of opportunity that must be met for the complete transition from the yeast to hyphal phenotype, as well as control strategies that can robustly prevent this transition. Our collaborators experimentally validated two of these control predictions in C. albicans strains lacking the transcription factor UME6 and the histone deacetylase HDA1, respectively. We expect this model will serve as a strong base from which to develop a systems biology understanding of C. albicans morphogenesis.
Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies, DJ Wooten, JGT Zañudo, D Murrugarra, AM Perry, A Dongari-Bagtzoglou, Reinhard Laubenbacher, Clarissa J Nobile, Réka Albert, PLoS computational biology 17 (3), e1008690 (2021)