| The genetic program encoded by DNA molecules is the source of information for all proteins responsible for cellular biochemistry. We now know the complete DNA blueprints of several eukaryotic organisms including man, which in principle allows the prediction of the primary structure of all their proteins. In addition, DNA contains the information required for regulating the amount and/or activity of the encoded proteins, controlling gene expression at many different levels. We are studying the biochemical function of proteins and the way these functions are controlled in the human yeast pathogens, Candida albicans and Cryptococcus neoformans. The incidence of life-threatening yeast infections has increased at a high rate during the last few decades, as a result of a growing number of patients whose immune system is compromised, for example as a result of chemotherapy, organ transplantation, or infection with human immunodeficiency virus. In the course of an infection, C. albicans switches from its yeast form to the hyphal form able to generate the massive forces needed for penetration, whereas C. neoformans turns into an intracellular parasite of phagocytes (such as macrophages). We wish to understand the molecular programme that enables these yeasts not only to survive but also to grow and multiply inside the human host. In particular, we wish to study how C. albicans and C. neoformans interact with the human immune system. Our work focuses on an intracellular compartment, the peroxisome, and an extracellular compartment, the cell wall. Both compartments are essential for a successful infection, because peroxisomes and lipid metabolism are vital for the supply of nutrients, whereas the cell wall is required for structural integrity. We attempt to understand how these compartments are formed and maintained in C. albicans and C. neoformans, applying knowledge gathered from studies with two model yeasts: budding yeast, Saccharomyces cerevisiae, and fission yeast, Schizosaccharomyces pombe. Since the complete genome sequence of all four yeasts is known, we are able to integrate bioinformatics and functional genomics approaches with more classical cell biology and biochemistry. Together, our research may have important clinical implications, because both peroxisomes and the cell wall form ideal targets for antifungal drug design. |
