This project will define critical steps in fungal growth for the development of antifungal agents, relevant to the agricultural industry and other economic sectors. Fungal cells regulate their growth in response to nutrient availability in part by controlling the abundance of molecules that can act as messengers within cells. One such class of messengers, inositol polyphosphates (InsPs), contribute to the control of cell shape and the resulting physical properties of fungal biofilm mats, resistant sheets of fungal cells that form on plastics and other solid surfaces. Little is known about the regulation of these InsP messengers or the cell components to which they attach. This research will provide missing molecular and biophysical detail regarding InsP messengers and their effect on fungal biology and growth. This level of understanding is fundamental for the development of new methods to control fungal overgrowth. From an educational perspective, undergraduate students from underrepresented backgrounds will have the opportunity to receive summer training in molecular and cellular biology for the analysis of InsPs. These students will also participate in departmental events and diversity workshops to provide them with the background and foundational resources to better succeed in graduate educational settings.
Cells use metabolite levels to signal conditions of nutritional stress for the regulation of cell shape, cell cycle progression, gene expression, and polarized growth, but the molecular basis of this signaling is incompletely understood. The yeasts S. cerevisiae and C. albicans are highly informative fungal models of cell signaling. Under conditions of nutrient limitation, yeast cells form extended and connected filaments as pseudohyphae, hyphae, and biofilms, through a signaling network recently found to involve the regulatory control of an important and conserved metabolite, inositol polyphosphate (InsP). InsPs are phosphorylated variants of the six-carbon inositol ring that regulate diverse cell processes. Pathways required for yeast cell growth and filamentation are required for wild-type InsP levels under conditions of nutrient limitation, and the genes encoding InsP biosynthetic enzymes are required for wild-type filamentation. In particular, the respective levels of pyrophosphorylated InsP species with doubly phosphorylated carbon residues in the inositol ring correlates strongly with the degree of filamentation in S. cerevisiae. This research will dissect the molecular mechanisms linking the regulation of filamentation and biofilm formation with InsP signaling. The molecular function of the conserved AMPK family kinase Snf1p in modulating activity of the InsP kinases Kcs1p and Vip1p will be determined. This research identifies the role of InsPs in controlling the protein composition and structure of the plasma membrane. The effect of InsP signaling on the filamentous morphology and rheological properties of biofilms in C. albicans will be quantified. Collectively, the project investigates conserved signaling pathways regulating InsP abundance and new downstream effectors of this regulatory network. Further, the research quantifies the effects of InsP signaling on the biophysics of C. albicans biofilms, presenting an important advancement in understanding the molecular basis of this economically significant fungal multicellular structure.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
