SSA - Elucidating the role of Endocytosis in Candida survival and proliferation in host cells

真菌，如念珠菌是医院获得性感染的主要原因，特别是在老年人和免疫功能低下的患者中，侵袭性念珠菌病与高死亡率有关。白色念珠菌毒力的核心是细胞在圆形酵母和丝状菌丝形式之间转换形状的能力。这种能力被认为允许生物体在血液中（如酵母）和通过组织（有菌丝）有效地传播。越来越多的证据表明，内吞途径参与了芽向菌丝转化的机制，并参与了菌丝极化生长的维持。这个项目将允许前所未有的深入了解白色念珠菌的环境适应性和与宿主细胞的相互作用机制。具体来说，学生将-1。探讨白色念珠菌内吞途径对巨噬细胞摄取后存活和增殖的重要性2。开发工具来研究巨噬细胞摄取后关键蛋白的表面水平3。使用斑马鱼模型系统来确定内吞受损的念珠菌是否可以在体内增殖和传播。总的来说，成功的学生将受益于国际公认实验室进行的多学科项目。他们将获得体外和体内细胞技术以及一系列先进显微镜方法的专业知识。

Fungi such as Candida species are a major cause of hospital-acquired infections especially in elderly and immuno-compromised patients, and invasive candidiasis is associated with a high mortality rate. Central to Candida albicans virulence is the ability of cells to switch shape between round yeast and filamentous hyphal forms. This capacity is thought to allow the organism to disseminate effectively in blood (as yeast) and through tissues (with hyphae). There is increasing evidence implicating the endocytic pathway in the mechanism for bud to hyphal transition, and in the maintenance of polarised growth in hyphae. This project will allow unprecedented insight into machinery underlying C.albicans environmental fitness and interaction with host cells. Specifically, the student will-1. investigate the importance of the C.albicans endocytic pathway for survival and proliferation following uptake by macrophages2. develop tools to investigate surface levels of key proteins following macrophage uptake 3. use a zebrafish model system to determine whether endocytically-compromised Candida can proliferate and be disseminated in vivo Overall, the successful student will benefit from a multi-disciplinary project to be undertaken within internationally-recognized laboratories. They will gain expertise in in vitro and in vivo cell techniques as well as in a range of advanced microscopy approaches.