Functional analysis of Candida glabrata Upc2A under hypoxia and a search for its chemical inhibitor

University Of Oklahoma Hlth Sciences Ctr, Oklahoma City OK

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Abstract

RESEARCH PROJECT SUMMARY RPL: Bao Vu, PhD Project Title: Functional analysis of Candida glabrata Upc2A under hypoxia and a search for its chemical inhibitor Adaptation to hypoxia is crucial for human pathogens like Candida glabrata, since the condition mimics the infection environment inside the host. 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. The transcription factor Upc2A is activated hypoxically, and its function is essential for C. glabrata hypoxic growth. Therefore, this application takes an interdisciplinary approach combining cutting-edge next generation sequencing 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 develop chemical inhibitors targeting the function of Upc2A. This knowledge will provide more understanding about C. glabrata physiology under hypoxic conditions and serve as a foundation for future antifungal therapy development against pathogenic fungi.