Keith Kozminski

Current research in the lab primarily focuses on the role of small G proteins in signal transduction during polarized cell growth. In particular, we are interested in how the Rho-family GTPase Cdc42p promotes protrusion of the cell cortex. In mammalian cells, the protrusions form filopodia and are essential for cell movement during processes such as neuronal migration, wound healing, and immune responses. In some fungi, these protrusions produce a daughter cell or bud. In each of these examples, Cdc42p asymmetrically organizes the actin cytoskeleton and, in turn, the secretory apparatus, prior to polarized growth. Thus, Cdc42p is a key regulator of polarized cell growth. Interestingly, to function properly, Cdc42p itself must acquire an asymmetric distribution on the cell cortex. This observation presents an important question: How does a protein that triggers the development of cellular asymmetry become asymmetrically distributed in the first place and remain asymmetrically distributed? To address this question, the lab has turned to the budding yeast S. cerevisiae (baker's yeast) as an experimental model for Cdc42p-dependent cell polarization. Budding yeast offers many experimental advantages. Among these are the amenability of this organism to classical genetics, molecular genetics, high throughput genomic/proteomic analysis, cell biology, and biochemistry. In addition, and very importantly, polarized cell growth and Cdc42p function in yeast is very similar to that found in mammalian cells. Thus, a less complex eukaryote such as yeast is being used to decipher how more complex eukaryotic cells (i.e., human) function.