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Cellular morphogeneisis in the human pathogen Candida albicans

Candida albicans is a major human pathogen. As well as being responsible for common mucosal infections such as thrush, it is responsible for life-threatening bloodstream and disseminated infections in immunocompromised and other groups of vulnerable patients.

Some surveys place C. albicans infections as the second most common cause of death from all hospital-acquired infections. It can grow in a variety of morphogenic forms ranging from unicellular yeast, chains of elongated cells known as pseudohyphae and finally true hyphae consisting of long tubes with parallel sides.

These different morphogenic forms are thought to be important in the infective process. We are studying the mechanisms that remodel cell growth during the formation of hyphae and pseudohyphae from unbudded yeast cells.

We use high resolution fluorescence microscopy to visualise the protein components of the polarised growth machinery in real time inside growing hyphae. This has allowed us to construct of a model of polarised hyphal growth in which secretory vesicles are transported along actin cables to accumulate in a subapical structure called the Spitzenkörper.

From there the vesicles are tethered at the cell surface by a multiprotein complex called the exocyst.

The focus of our current research is to understand how hyphal growth is controlled by the action of protein kinases.

We have identified the particular kinases and the proteins they target. We have investigated the physiological role of these phosphorylation events by mutating the phosphoacceptor sites in the target proteins to residues that either mimic phosphorylation, so the proteins behave as if they were permanently phosphorylated, or to non-phosphorylatable residues to investigate the consequences of the absence of phosphorylation.

We are now employing Mass Spectroscopy-based methods to carry out unbiased, proteome-wide surveys of the targets of kinases known to be essential for hyphal growth.