Cells often respond to environmental cues by utilizing mitogen-activated protein (MAP) kinase cascades to regulate the expression of genes responsible for the appropriate cellular response. The experiments that I am proposing to conduct seek to advance the understanding of how cells sense environmental stress, activate the appropriate MAP kinase cascade, and then deactivate the cascade once the cell has responded. Nitrogen starvation induces the formation of pseudohyphae in S. cerevisiae via a MAP kinase cascade that shares components with a MAP kinase cascade triggered by high extracellular osmolarity. Studies from the Herskowitz lab have identified Sho1p as a potential sensor for nitrogen starvation in addition to its established role as a sensor of osmolarity. I will carry out genetic screens to identify other proteins involved in sensing low nitrogen. In addition, I shall investigate how Sho1p signaling is regulated to prevent constitutive activation of the high osmolarity glycerol and pseudohyphal growth pathways. Finally, using chemically inhibitable versions of the MAPK Hog1p in conjunction with DNA microarrays, I will identify genes regulated by Hog1p during both stress and non-stress conditions.
| Westfall, Patrick J; Patterson, Jesse C; Chen, Raymond E et al. (2008) Stress resistance and signal fidelity independent of nuclear MAPK function. Proc Natl Acad Sci U S A 105:12212-7 |
| Westfall, Patrick J; Ballon, Daniel R; Thorner, Jeremy (2004) When the stress of your environment makes you go HOG wild. Science 306:1511-2 |
