Systems Biology of the hypoxic adaptation

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A critical but poorly understood aspect of an eukaryotic organism is the ability to sense and adapt to variations in the oxygen concentration in the local environment. Hypoxia is a state of a reduced oxygen availability that is experienced by many organisms under numerous physiological and disease conditions. Hypoxia leads to a substantial remodeling of cell metabolism in addition to a reduction of energy production and thus, organisms must develop sophisticated mechanisms to cope with oxygen depletion. The aim of our project is to understand how oxygen depletion is sensed and to identify biological processes that are essential for adaptation in such environment. We opt to study these aspects in Candida albicans, which is a unicellular eukaryotic organism that has a dual normoxic and hypoxic lifestyle. C. albicans is a commensal yeast that inhabits both aerobic human body sites including skin and mucosal surfaces, as well as oxygen-poor locations such as internal organs. Thus, C. albicans is an attractive model to study metabolic and growth adaptations in response to oxygen fluctuations. We will undertake a systematic genetic screen to identify genes required for the perception and the adaptation to oxygen depletion. The candidate genes will be functionally characterized and their role in mediating hypoxia adaptation will be dissected using different genetic and genomic approaches. Our preliminary investigations are supportive of a model where hypoxia is sensed through gauging the drop of cellular energy (ATP) generated by mitochondria. This hypothesis will be tested by different complementary approaches using genetic, chemogenomic and cellular biology tools. Hypoxia is a biological state related to different clinical problems associated with many health disorders such as ischemic heart disease, cerebral ischemia, cancers and obstetrical/perinatal complications etc. Hypoxia is also a critical factor in food industry affecting mainly fermentative bioprocess and aquaculture farming. Thus, this project will generate fundamental knowledge on the biology of hypoxia that can be translated to other field of application including biotechnology and medicine.