OXYGEN SENSING SIGNED

Project "OXYGEN SENSING" data sheet

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 Project objective

Oxygen (O2) levels can vary enormously in the environment, which induces dramatic behavioral and physiological changes to resident animals. Adaptations to O2 variations can be either acute or sustained. How animals detect and respond to the changes of O2 availability remains elusive at the molecular level. In particular, what is the precise mechanism of acute O2 sensing, what are the primary sensor for acute hypoxia, and why do neurons of various species exhibit completely different sensitivity to hypoxic challenges? The research proposed here aims at addressing these intriguing but challenging questions in the model system nematode C. elegans, which offers unique advantages to systematically dissect O2 sensing at both genetic and neural circuit levels. C. elegans responds dramatically to acute O2 variations by altering its locomotory speed. We will make use of this robust behavioral response to O2 stimulation for high-throughput genetic screens, aiming to identify a collection of molecules critical for acute O2 sensing. These molecules will be subsequently characterized in the context of a well-described nervous system of C. elegans. Our findings will offer the opportunity to shed light on conserved principles of acute O2 sensing that are operating in the O2 sensing systems in humans such as carotid body. In addition to its robust responses to O2 variation, C. elegans exhibits remarkable tolerance to a complete lack of O2, anoxic exposure. My team will thoroughly investigate anoxia tolerance of C. elegans by performing a screen for anoxia-sensitive mutants that has previously been challenging. The discoveries will allow us to delineate the molecular underpinning of anoxia tolerance in C. elegans, and to inspire other researchers to develop better strategies to cope with hypoxic challenges caused by certain diseases such as stroke and ischemia, which are the most causes of human deaths in developed countries.