MAPPING PHOSPHORYLATION OF A CANDIDA ALBICANS VIRULENCE FACTOR

白色念珠菌毒力因子磷酸化图谱

• 批准号: 8365805
• 负责人: SUZANNE M NOBLE
• 金额: $ 0.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365805
• 关键词: Animal Model; Biology; Blood Circulation; Candida albicans; Cells; Environment; Fission Yeast; Funding; Fungal Genome; Gastrointestinal tract structure; Genes; Grant; Iron; Maps; Modification; National Center for Research Resources; Organism; Phosphorylation; Principal Investigator; Research; Research Infrastructure; Resources; Source; Transcription Coactivator; United States National Institutes of Health; Virulence Factors; Yeast Model System; Yeasts; cost; feeding; insight; interest; pathogen; transcription factor; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. All pathogens struggle to obtain iron from the host bloodstream, whereas commensal organisms of the mammalian gastrointestinal tract must struggle with a surfeit of iron. The commensal-pathogenic yeast Candida albicans manages to succeed in both environments through previously unknown mechanisms. We discovered that unlike other model organisms like S. pombe, C. albicans inserts a transcriptional activator called Sef1 between two more broadly conserved transcriptional regulators, a repressor of iron uptake genes called Sfu1 and a repressor of iron utilization genes called Hap43. These three transcription factors form a feed-forward circuit that is distinct from those described in nonpathogenic model yeasts. Interesting, we found that Sef1 undergoes post-transcriptional modification when the cells are shift from high iron to low iron environments and our preliminary results suggest that phosphorylation may contribute to this modification. Mapping Sef1 phosphorylation will yield insight into the mechanisms regulating iron acquisition in this commensal-pathogenic yeast.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 所有病原体都难以从宿主血液中获取铁，而哺乳动物胃肠道的共生生物必须与过量的铁作斗争。 共生致病酵母白色念珠菌通过以前未知的机制在这两种环境中都取得了成功。我们发现，与其他模式生物（如粟酒裂殖酵母）不同，白色念珠菌在两个更广泛保守的转录调节因子（称为 Sfu1 的铁摄取基因阻遏物和称为 Hap43 的铁利用基因阻遏物）之间插入了一个名为 Sef1 的转录激活子。这三个转录因子形成一个前馈回路，与非致病性模型酵母中描述的回路不同。有趣的是，我们发现当细胞从高铁环境转移到低铁环境时，Sef1 会发生转录后修饰，我们的初步结果表明磷酸化可能有助于这种修饰。绘制 Sef1 磷酸化图谱将深入了解这种共生致病酵母中调节铁获取的机制。