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

活细胞可以忍受环境的广泛变化。有几种信号机制可以检测环境变化，从而激活适当的反应。我们已经确定了Ypp1，面包酵母中的一种蛋白质，它是一种有助于维持真菌细胞壁的特定信号通路的关键调节剂。人类细胞没有细胞壁，因此这种结构被认为是开发对人类无毒的抗真菌剂的主要目标。致病真菌和面包酵母中的信号通路是相似的，因此我们将使用面包酵母作为模式生物来研究Ypp1在维持真菌细胞壁完整性中的作用。Ypp1影响信号传导的确切性质将通过测量所涉及的信号传导途径的关键生化中间体来确定。随后将评估Ypp1的缺失如何影响信号通路激活的反应，重点是细胞壁的化学结构如何被重新建模。此外，由于面包酵母的基因组可以轻松操纵，我们将确定涉及Ypp1作用的途径和蛋白质。通过这种方式，我们将确定抗真菌药物设计的其他目标。

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.