白念珠菌是临床极为重要的条件性致病真菌，探索其致病机制具有重要意义。Spf1是本实验室从白念珠菌中鉴定出的内质网钙泵，介导胞质钙向内质网腔的转运，在细胞离子稳态维持、内质网压力耐受、形态发生调控方面扮演重要角色，但其作用机制尚未明确。内质网-质膜连接是近年发现的一类新型膜连接复合体，参与内质网与质膜的物质与信息交换，在蛋白与脂质运输、信号转导、离子转运等诸多方面发挥关键作用。本项目通过系统鉴定白念珠菌内质网-质膜连接蛋白，构建连接蛋白缺失株与内质网-质膜连接定位体系，结合共聚焦显微镜观察、透射电镜观察、双分子荧光互补分析等手段，从调控内质网-质膜连接的角度深入探索Spf1对钙信号途径、形态发生途径等关键信号通路的调控机制，以及内质网-质膜连接在促进白念珠菌内质网与质膜之间物质及信号交换方面的作用，同时发掘针对白念珠菌的新型药物靶点，为临床治疗其感染提供新的理论依据。

Candida albicans is one of the most important opportunistic fungal pathogens in clinic. It is of significance to investigation of its pathogenicity mechanisms. Spf1 is the endoplasmic reticulum (ER) calcium pump identified by our group. This protein mediates calcium transport from the cytoplasm to the ER, and plays an important role in maintenance of ion homeostasis, stress tolerance and morphogenesis. However, its function mechanisms remain unknown. ER-PM contact is a novel kind of membrane contact system, mediating exchange of materials and signals between the ER and the plasma membrane (PM), and thus is involved in transport of proteins and lipids, signaling transduction and ion transport. In this study, by systematically identification of ER-PM contact proteins, construction of contacting protein mutants and ER-PM contact indicators, confocal microscopy, transmission electron microscopy and BiFC analysis, we will explore the mechanisms by which Spf1 regulates the key signaling pathways, i.e., the calcium signaling pathway and the morphogenesis pathway, and uncover the role of the ER-PM contact in promotion of the exchange of materials and signals. Furthermore, this study aims to discover new antifungal targets and shed a novel light on development of antifungal therapy.