The aim of my research is to understand how the cell cycle is regulated and coordinated with differentiation. In one program, we investigate cell cycle control and development in Candida albicans, one of the most common fungal pathogens of humans. C. albicans differentiates into several cell types, including yeast, pseudohyphae or hyphae. This trait is crucial for virulence; cells locked in one form are significantly less pathogenic. Cell cycle signals have profound effects on differentiation and polar morphogenesis in C. albicans, but the basic cell cycle circuitry and mechanisms linking it with development are not well defined. We specifically investigate regulatory aspects of the G1/S transition, mitosis and polar morphogenesis. Our work revealed distinct features that have important implications for new drug target discovery and controlling growth of the pathogen. In a second program, we focus on the roles of a polo-like kinase, PLKA, in cell cycle regulation and development of the filamentous fungus Aspergillus nidulans. Polo-like kinases are multi-functional cell cycle regulators in yeast to humans, up-regulated in many cancers, and play additional roles in metazoan development. We identified PLKA in A. nidulans, which is the only filamentous fungal polo-like kinase characterized to date, and demonstrated that it has many novel functions, including negatively regulating sexual development. Phylogenetic analyses suggest that filamentous fungal polo-like kinases are a distinct group, which has important implications for the evolution of the polo-like kinase family.
