A novel splicing program that controls cancer cell metastasis

微生物感染每年造成400多万人死亡，侵袭性真菌感染的死亡率在40-90%之间。尽管侵袭性真菌感染的重要性、高死亡率和有限的治疗选择，但与细菌和病毒感染相比，我们对真菌毒力的了解尚处于起步阶段。随着抗真菌药物耐药性的增加（由于出现多重耐药菌株，世卫组织已将耳念珠菌宣布为全球健康威胁），迫切需要确定新的抗真菌药物靶点。为了能够引起感染，微生物必须与宿主的先天免疫系统竞争。微生物和免疫系统之间持续的军备竞赛导致病原体进化出逃避和逃避免疫系统作用的机制。到目前为止，我们已经表明机会性人类真菌病原体白色念珠菌已经进化出两种先天免疫逃避策略。第一种是通过隐藏高免疫原性碳水化合物-葡聚糖，第二种是通过抑制人体替代补体系统。然而，Hall小组最近的工作已经确定了一种新的，尚未被描述的，白色念珠菌的先天免疫逃避策略。本博士的目的是描述和定义这种新型先天免疫逃避策略背后的分子机制。将Hall实验室的真菌分子生物学和宿主-病原体相互作用专业知识与Skipp实验室的全球转录组学和蛋白质组学方法相结合，您将确定促进真菌先天免疫逃避的宿主环境条件，确定参与该过程的关键蛋白质，并揭示导致免疫逃避的调节信号通路。因此，该项目将提供昂贵的微生物学、分子生物学、显微镜和免疫学技术培训，以及大型数据集的生物信息学分析。

Microbial infections result in the death of over 4 million people/year, with the mortality rate of invasive fungal infections ranging between 40-90%. Despite the prominence, high mortality rates, and limited treatment options for invasive fungal infections, our understanding of fungal virulence is in its infancy compared to bacterial and viral infections. With antifungal resistance on the increase (Candida auris has been declared a global health threat by the WHO due to the emergence of multi-drug resistant strains), there is an urgent need to identify novel antifungal drug targets. To be able to cause infections microbes must compete with the host's innate immune system. The continued arms race between microbes and the immune system has led to pathogens evolving mechanisms to evade and escape the actions of the immune system. To date, we have shown that the opportunistic human fungal pathogen Candida albicans have evolved two innate immune evasion strategies. The first is through the concealment of the highly immunogenic carbohydrate beta-glucan, and the second is through the inhibition of the human alternative complement system. However, recent work in the Hall group has identified a new, as yet to be described, innate immune evasion strategy in C. albicans. The aim of this PhD is to characterise and define the molecular mechanism behind this novel innate immune evasion strategy. Combining the fungal molecular biology, and host-pathogen interaction expertise of the Hall lab with global transcriptomics and proteomics approaches from the Skipp lab, you will identify the host environmental conditions that promote fungal innate immune evasion, identify the key proteins involved in the process, and unravel the regulatory signalling pathways that lead to immune evasion. Therefore, this project will provide expensive training in microbiology, molecular biology, microscopy and immunology techniques, as well as bioinformatic analysis of large data sets.