Office Address: 208 PLSB
Lab: (434) 924-3943

Education

B.A. and B.S., State University of New York, Buffalo, 1989
Ph.D., Yale University, 1995
Postdoctoral Research, U. of California, Berkeley, 1995-2001

Research Interests

Current research in the lab focuses on the molecular mechanisms that regulate asymmetric or polarized cell growth. The formation of a daughter cell by the baker's yeast S. cerevisiae, via budding of the cell cortex, is our experimental model.  Study of yeast budding is important for two reasons.  First, many organisms depend upon polarized cell growth for life, relying upon the cellular asymmetry generated by polarized cell growth to support cellular specializations that confer a selective advantage (e.g., root hairs in plants,  axons of nerve cells, microvilli of intestinal epithelia, hyphae in fungi).  Regulation of polarized cell growth is critical.  Death of an individual organism or the inability to propagate is a common outcome of mis-regulated polarized cell growth, ensuing from defects in development, tissue failure, or errors in cell division. Polarized cell growth in yeast and mammalian cells share many commonalities on the molecular level. Thus, use of a less complex eukaryote such as yeast allows us to decipher how more complex eukaryotic cells such as human cells function.  Second, knowledge of polarized cell growth will provide blueprints for innovations in synthetic biology and engineering. Currently, there are few, if any, engineering systems in which control modules self-organize from diffusible molecules as they do in polarized cell growth.  While many key processes in polarized cell growth are known (e.g., selection of a growth site, establishing an axis of polarity, polarized exocytosis), the molecular picture of how these processes are interconnected and regulated by diffusible molecules is far from complete. Budding yeast offers many experimental advantages toward deciphering the links between these processes. These advantages include the strong amenability of S. cerevisiae to classical genetics, molecular genetics, high throughput genomic/proteomic analysis, cell biology, and biochemistry. 

Research questions currently under investigation in the Kozminski Lab include the following:

1.  How does a cell maintain a sufficient concentration of activated Cdc42p, a small GTPase that is a potent morphogenic regulator, at sites of polarized growth so as to maintain a stable axis of growth?

2.  What are the molecular events that link polarized exocytosis with cell cycle progression?

3.  How do lipid binding proteins such as oxysterol binding proteins (OSBPs) regulate polarized exocytosis and, in turn, polarized cell growth?

Representative Publications 

Heckle, L.A. and K.G. Kozminski. 2023.  Osh-dependent and -independent Regulation of PI4P Levels During Polarized Growth of Saccharomyces cerevisiae.  Molecular Biology of the Cell.  In press.

Smindak, R.J., L.A. Heckle, S.S. Chittari, M.A. Hand, D.M. Hyatt, G.E. Mantus, W.A. Sanfelippo, and K.G. Kozminski. 2017.  Lipid-dependent regulation of exocytosis in S. cerevisiae by OSBP Homologue (Osh) 4.  Journal of Cell Science 130: 3891-3906.  Read Paper.  Read Highlight.

ARCHIVED PUBLICATIONS