Transcriptomic and proteomic analyses of Upc2A under Candida glabrata hypoxic growth

光滑念珠菌低氧生长下 Upc2A 的转录组学和蛋白质组学分析

• 批准号: 10976654
• 负责人: Bao Gia Vu
• 金额: $ 10.1万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10976654
• 关键词: Transcriptomic; proteomic; analyses; Upc2A; under

Adaptation to hypoxia is crucial for human pathogens like Candida glabrata, since the condition mimics the infection environment inside the host. Hence, our long-term goal is to identify essential factors that are required for C. glabrata hypoxic growth, and to exploit them for novel Candida drug development. However, the transcriptional responses of C. glabrata shifting from normoxic respiratory to hypoxic metabolism is unexplored. My recent work has indicated that the transcription factor Upc2A is activated hypoxically, and its function is essential for C. glabrata hypoxic growth. Although Upc2A roles in C. glabrata drug resistance mechanism is well characterized, its intrinsic function in C. glabrata biology remains under-studied. This application takes an interdisciplinary approach combining cutting-edge next generation sequencing, proteomics, and molecular genetic techniques to determine the fundamental function of Upc2A in C. glabrata hypoxic physiology. Our overall objectives are (i) to decode the comprehensive interaction networks of Upc2A target genes as well as genes that are required for C. glabrata hypoxic adaptation, and (ii) to identify Upc2A-associated proteins required for the activity of this transcription factor and the organism’s hypoxic growth. This knowledge will provide more understanding about C. glabrata physiology under hypoxic growth conditions which could ultimately be translated into the pathogenesis of this organism inside the host.

适应缺氧对于像念珠菌（如念珠菌）的病原体至关重要，因为这种情况 模仿宿主内部的感染环境。因此，我们的长期目标是确定 C. glabrata低氧生长所需的基本因素，并将其利用为新颖 念珠菌药物开发。然而，glabrata C. glabrata的转录响应从 对低氧代谢的常氧呼吸是出乎意料的。我最近的工作表明 转录因子UPC2A被低氧激活，其功能对于C。 Glabrata低氧增长。尽管UPC2A在C. glabrata耐药性机制中的作用很好 特征是，其在Glabrata C. glabrata生物学中的内在功能仍然不足。此应用程序 采用跨学科的方法，结合了尖端的下一代测序， 蛋白质组学和分子遗传技术，以确定UPC2A的基本功能 在C. glabrata缺氧生理学中。我们的整体目标是（i）解码全面 UPC2A靶基因的相互作用网络以及glabrata所需的基因 低氧适应和（ii）以识别其活性所需的UPC2A相关蛋白 转录因子和生物体的低氧增长。这些知识将提供更多 了解在低氧生长条件下的Glabrata生理学 最终将其转化为宿主内部这种生物的发病机理。