Fungi are a major kingdom among the eukaryotes and have a great impact on life. Yeast cause bread to rise or juice to ferment to wine or beer, and fungal symbiotes may be necessary for optimal growth of many plants. However, fungi can also be harmful. Fungal diseases destroy much of the world's food crop, and human fungal infections are often the immediate cause of death in cancer and AIDS victims.
Unlike animal cells, fungal cells are surrounded by thick cell walls, the structure and synthesis of which affect all their interactions with other cells. For instance, mating in fungi requires proteins on the surface of the walls for recognition and binding to cells of opposite mating type. With support from the National Institutes of Health, Peter Lipke, Professor of Biochemistry and Biology at The Graduate Center and Hunter College, and his research group have been studying these wall-bound recognition proteins for many years. In bakers' yeast, the sexual agglutinins bind together the two mating types. Each sex expresses one type of agglutinin, and these complementary proteins bind to each other to potentiate the mating response. The Lipke group has discovered that certain sub-structures in these proteins recognize each other. One of the proteins has a structure like immunoglobulins, a very common class of recognition proteins that also mediate cell-cell recognition and signaling in our own immune systems.
A related set of proteins cause the pathogenic yeast Candida albicans to adhere to our mucous surfaces. This adhesion is the first step in the development of yeast infections, including vaginal candidiasis and thrush. These pathogenic adhesions have an extra structure that is not present in the proteins from bakers' yeast. This additional structure causes the yeast to congregate and grow as colonies on and in our tissues. We are determining the structural basis for this broad binding specificity.
Professor Lipke's laboratory is also interested in how fungi synthesize and assemble their cell walls, which can be 30% of the cell mass. They find that the pathway used by bakers' yeast is common to many pathogenic and environmentally important fungi. Using cell adhesion proteins and fluorescent tracking proteins, the scientists are following the genesis of these wall proteins from the ER to the Golgi to the membrane and finally to the wall, as well. The goals are to elucidate biochemical reactions unique to wall assembly, and then to evaluate these steps as targets for antifungal drugs. Utilizing techniques in molecular engineering, microscopy, protein purification, bioinformatics, structural biochemistry, and detailed binding analyses, the lab currently has 12-15 people, including undergraduates, graduate students, and post-doctoral associates. The research is a component of the $9.9 million grant (approx 2.4 M per year) from the National Institutes of Health for the Support for Continuous Research Excellence (SCORE) Program, which funds 25 Hunter research labs.