Phosphoinositide signalling and fungal cell wall integrity: investigating the essential role of the conserved protein Ypp1

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Living cells can tolerate extensive changes to their environment. Several signalling mechanisms exist which detect environmental changes, leading to activation of an appropriate response. We have identified Ypp1, a protein in baker's yeast, that is a key modulator of a particular signalling pathway contributing to maintenance of the fungal cell wall. Human cells don't have a cell wall, so this structure is regarded as a principal target for the development of antifungal agents which are non-toxic to humans. Signalling pathways in pathogenic fungi and baker's yeast are similar, so we will use baker's yeast as a model organism for investigating the role of Ypp1 in maintaining fungal cell wall integrity. The precise nature by which Ypp1 affects signalling will be determined, by measuring key biochemical intermediates of the signalling pathway involved. This will be followed by assessing how loss of Ypp1 affects the responses activated by the signalling pathway, with emphasis on how the chemical structure of the cell wall is re-modelled. Also, because the genome of baker's yeast can be manipulated with ease, we will identify pathways and proteins that involve the action of Ypp1. In this way, we will identify additional targets for antifungal drug design.