Temperature control of the C. elegans circadian clock Daily (circadian) rhythms control multiple aspects of human behavior and physiology (e.g. sleep, body temperature) and disruption of these rhythms can either cause or affect the severity of most neurological disorders such as stroke and Alzheimer's disease. These circadian rhythms are driven by clocks in our brain and body that can be entrained by daily light and/or temperature cycles. In depth analyses have identified the physiological mechanisms comprising these light-entrained clocks in humans and most model organisms studied, but how temperature information controls these clocks is unclear. Our research has established the nematode Caenorhabditis elegans as a powerful genetic model system to study temperature control of the clock. In this proposed research, we will use genetic and genomic approaches as well as real-time imaging in C elegans to investigate the molecular mechanisms and neural pathways underlying temperature control ofthe circadian clock.
Specific Aim 1 will develop a new real-time imaging system for recording and quantifying circadian rhythmicity in behavior and gene expression in freely moving C elegans. This imaging will be useful for mutant analysis and genetic screening of clock mutants.
Specific Aim 2 will define the sensory neuron types that transmit temperature information to the clock(s). This will aid in understanding the sensory pathways that process and integrate environmental information to the clock.
Specific Aim 3 will define the molecular components ofthe clock. These components are expected to encode for core-clock genes and components that process temperature information from the core-clock to clock-output genes.
Specific Aim 4 will identify circadian genes expressed in single sensory neuron types with mRNAsequencing. Identification ofthe complete set of sensory genes regulated by the C elegans clock will determine the behavioral consequences of differential expression of genes that process environmental information to the clock. Understanding the inner workings ofthe circadian clock in great depth and the impacts on circadian time keeping should provide us with new avenues of treatment or prevention of neurobehavioral consequences of disrupted circadian timing.
Studying the biological clock and impacts on biological time keeping will ultimately lead to strategies for treatment and prevention of neurological disorders where disturbances in timing are important causes of morbidity.
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