Cell wall structure and biogenesis
Role of GPI anchors in fungal cell walls. We discovered that GPI anchors cross-link many
cell wall proteins to the glucans. This was the basis for the current models of fungal cell walls.
Two reviews summarize our knowledge:
Gonzalez, M., P.W.J. de Groot, F.M. Klis, and P.N. Lipke. 2009. Glycoconjugate
Structure and Function in Fungal Cell Walls. In A. Moran, P. Brennan, O. Holst and
F. von Itzstein (eds.) Microbial Glycobiology: Structures, Relevance, and
Applications. Elsevier. pp. 169-183.
Gonzalez, M., P.N. Lipke, and R. Ovalle. 2009. GPI Proteins in Biogenesis and structure
of yeast cell walls. In The Enzymes vol 26, Glycosylphophatidylinositol (GPI)
anchoring of proteins, eds. Menon, Kinoshita, Orlean and Tamanoi, Academic
Press/Elsevier pp. 321-355.
A 2010 paper and a patent application are the start of our ideas to exploit this knowledge
to find drug targets to ameliorate fungal infections.
Gonzalez, M., N. Goddard, C. Hicks, R. Ovalle, C.K. Jue, and P.N. Lipke. 2010. A
Screen for Deficiencies in GPI-Anchorage of Wall Glycoproteins in Yeast. Yeast 27:
583-596.
Link to cell wall assembly cartoon
We are currently engaged in searches for ways to interfere with this anchorage, as an opening to
discovery of new antifungal drugs.
Other Papers:
Kipnis, P., Thomas, N., Ovalle, R. and Lipke, P.N. 2004. The v-SNARE Bet1p is required for cell
wall cross-linking of S. cerevisiae a-Agglutinin. Microbiology 150: 3219-3228.
Lipke, P.N. and R. Ovalle. 1998. Yeast Cell Walls: New Structures, New Challenges. J. Bacteriol.
180: 3735-3740
With Dr. Rafael Ovalle, we are also investigating how oxidative drugs destroy
fungal cell walls and developing analytic techniques to characterize the products of oxidation.
Ovalle, R., C. Soll, F. Lim, C. Flanagan, T. Rotunda, and P.N. Lipke. 2001. Systematic analysis of
oxidative degradation of polysaccharides using PAGE and HPLC/MS. Carbohydrate Res. 330:
131-139.
Ovalle, R., M. Spencer, M. Thiwamont, and P.N. Lipke. 1999. The spheroplast lysis assay for
yeast in microtiter format. Applied Environ. Microbiol. 65: 3325-3327
Ovalle, R., S.T. Lim, B. Holder,C.K. Jue, C. Wood Moore, and P.N. Lipke. 1998. Spheroplast rate
assay for determination of cell wall integrity in yeast. Yeast 14: 1159-1166