UCSF

Complex emergent biological behavior requires coordinated activity among an entire genome’s biomolecules. Cells respond to changes in environmental conditions by activating signaling pathways and gene expression programs to maintain homeostasis. Here, we first present a synthetic tool that can either dynamically regulate the expression levels of two genes independently or regulate the log mean and variance of a single gene’s expression. We then present the use of similar tools to perturb and produce a large dataset of perturbed, whole genome, gene expression measurements to explore the relationship between environmental stresses, kinase signaling, and global gene expression in S. Cerevisiae. With these data, we reconstructed canonical stress pathways, identified examples of crosstalk among pathways, and implicated numerous kinases in novel environment-specific roles. Specifically, we investigated how individual kinases tuned the magnitude of induction of the environmental stress response (ESR) in environment-specific ways. Our findings suggest that the ESR integrates inputs from multiple sensory kinases to modulate gene expression and growth control.