Transcriptomic and proteomic analyses of Upc2A under Candida glabrata hypoxic growth

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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.