Transcriptomic and proteomic analyses of Upc2A under Candida glabrata hypoxic growth

适应缺氧对于光滑念珠菌等人类病原体至关重要，因为这种情况 模仿宿主体内的感染环境因此，我们的长期目标是确定 C.所需的基本因素。glabrata低氧生长，并利用它们作为新的 念珠菌药物开发。然而，C. glabrata从 常氧呼吸到低氧代谢尚未探索。我最近的研究表明， 转录因子Upc2A在缺氧条件下被激活，其功能是C. 光叶苔低氧生长。虽然Upc2A在C.光滑果耐药机制良好 特征，其内在功能在C.光果草生物学仍处于研究阶段。本申请 采用跨学科的方法，结合尖端的下一代测序， 蛋白质组学和分子遗传学技术来确定UPC2A的基本功能 in C.光叶苔缺氧生理学我们的总体目标是（i）解码全面的 Upc2A靶基因以及C.光滑 低氧适应，和（ii）鉴定UPc 2A相关蛋白的活性所需的这种 转录因子和生物体的缺氧生长。这些知识将提供更多 了解C。光滑的生理学在缺氧的生长条件下， 最终转化为宿主体内这种生物的发病机制。

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.