PHOSPHOLIPASE B: A VIRULENCE FACTOR FOR CANDIDA GLABRATA

描述(改编自申请摘要)：在本K08申请中， 科尼利厄斯·克兰西请求3年的支持，以学习必要的技能 实现他成为一名成功的临床医生-科学家的职业目标。这个 申请者的长期研究兴趣是识别和研究 酵母致病菌光滑假丝酵母的毒力因子 美国的血液真菌感染。光肩星毛藻是一种典范 研究分子遗传学的有机体，因为它有单倍体基因组和 与酿酒酵母有密切的亲缘关系。申请人S实验室 细胞外磷脂酶B(PLB)活性水平与 光滑毛囊线虫侵袭性感染在人类中的严重性。他假设 CgPLB2基因对光肩星天牛S的PLB活性有很大影响，并且 CgPLB2的破坏将显著降低病毒的毒力 有机体。申请者S的短期目标是最终证明 CgPLB2通过实现Koch‘s的分子形式在毒力中发挥重要作用 假设。具体地说，他将完成克隆cgPLB2，证明 破坏cgPLB2引起的PLB活性降低可减弱毒力 在播散性感染的小鼠模型中，并展示了修复 通过重新插入cgPLB2来抑制PLB的活性可以恢复毒力。正在完成 在这个项目中，他将学习广泛的分子生物学技术， 生物化学和播散性感染的动物模型。此外，他 将学会表述假设，设计适当的实验，应用 统计工具，并解释数据。这些技能将得到以下补充 包括基础科学课程和高级研讨会的教育计划 和统计数据。他将接受多学科的培训 环境由医学系和安大略省医学部资源支持 佛罗里达大学分子遗传学和微生物学 由他的导师阿尔弗雷德·勒文(一位酵母遗传学家)和他的合作导师密切合作， Frederick Southwick(传染病科主任，微生物专家 发病机制和细胞生物学)。

DESCRIPTION (adapted from application abstract): In this K08 application, Cornelius Clancy requests 3 years of support to learn the skills necessary to achieve his career goal of becoming a successful clinician-scientist. The applicant's long-term research interest is in identifying and studying virulence factors for the yeast pathogen Candida glabrata, now a leading bloodstream fungal infection in the United States. C. glabrata is a model organism for studying molecular genetics because it has a haploid genome and is closely related to Saccharomyces cerevisiae. The applicant s laboratory has correlated levels of extracellular phospholipase B (PLB) activity with the severity of C. glabrata invasive infections in humans. He hypothesizes that the gene cgPLB2 is responsible for much of C. glabrata s PLB activity, and that disruption of cgPLB2 will significantly reduce the virulence of the organism. The applicant s short-term goal is to conclusively prove that cgPLB2 is important in virulence by fulfilling the molecular form of Koch's postulates. Specifically, he will finish cloning cgPLB2, demonstrate that the reduction of PLB activity caused by disruption of cgPLB2 attenuates virulence in a murine model of disseminated infection, and demonstrate that restoration of PLB activity by reinsertion of cgPLB2 restores virulence. In completing this project, he will learn a wide range of techniques in molecular biology, biochemistry, and animal models of disseminated infections. In addition he will learn to formulate hypotheses, design appropriate experiments, apply statistical tools, and interpret data. These skills will be complemented by an educational plan including courses and advanced seminars in basic sciences and statistics. He will receive this training in a multidisciplinary environment supported by the resources of the Dept of Medicine and the Dept of Molecular Genetics and Microbiology at the University of Florida, guided closely by his mentor, Alfred Lewin (a yeast geneticist) and his co-mentor, Frederick Southwick (Chief of Infectious Diseases and an expert in microbial pathogenesis and cell biology).