Morphogenesis and iron acquisition in pathogenic fungi
human host environment. Candida albicans is the most common systemic fungal pathogen, increasingly prevalent among immunosuppressed patients. Investigations in our laboratory focus on two distinct adaptations of this organism to the host environment: the ability to change shape under different conditions between yeast and mold morphologies, enabling it to spread, attach and penetrate host tissues; and the ability to extract iron from host hemoglobin. With regard to morphogenesis, we are focusing on regulators that inhibit the switch from yeast to mold. We have identified a role for phosphorylation and ubiquitin-mediated degradation of specific cellular proteins in the suppression of this morphogenetic switch. Regarding hemoglobin iron acquisition, we have identified a network of specialized cell surface heme-binding proteins, and are characterizing the mechanism by which these extracellular heme receptors function within the pathway of hemoglobin-iron uptake into the cell, using methods of structural biology, biophysics and subcellular imaging. We anticipate that molecular understanding of the factors required for Candida albicans virulence will lead ultimately to new ways to combat human infection.
– Systematic analyses of kinase and phosphatase function in Candida albicans , collaboration with Rob Arkowitz (CNRS Nice) and Joachim Morschhauser (U. Wurzburg).
– Pharmacological inhibition of Candida albicans morphogenesis, with Steve Kron (U. of Chicago).
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