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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 所有病原体都努力从宿主血液中获得铁，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先前未知的机制在这两种环境中成功地获得了成功。我们发现，与庞氏葡萄球菌等其他模式生物不同，白色念珠菌会在两个更保守的转录调控因子之间插入一种名为Sef1的转录激活因子，一种是铁吸收基因的抑制因子Sfu1，另一种是铁利用基因的抑制因子Hap43。这三个转录因子形成了一个前馈电路，与非致病模型酵母中描述的不同。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经历了转录后修饰，我们的初步结果表明，磷酸化可能有助于这种修饰。绘制Sef1磷酸化图谱将有助于深入了解这种共生致病酵母中铁获取的调控机制。