Daily (circadian) rhythms control multiple aspects of human behavior and physiology (e.g. sleep, mood, body temperature), and disruption of these rhythms can either cause or affect the severity of most neurological disorders. Circadian rhythms are driven by clocks in our brain and body that can be entrained by daily light and/or temperature cycles. Mechanisms comprising these light-entrained clocks in humans and most model organisms studied are well known, but how temperature signals control these clocks is poorly understood. Recent studies in mammals have demonstrated that natural body temperature cycles are crucial entrainment signals for keeping peripheral body clocks in sync. Our research has discovered for the first time circadian genes entrained by temperature cycles in the model organism Caenorhabditis elegans, establishing this animal as a new model in the clock field for studying the temperature-entrained clock(s). C. elegans is a well- established system to study temperature responses;it has a well-mapped neural circuitry that senses small changes in temperature, and exhibits circadian behavior induced by temperature cycles. This proposal will use real-time imaging combined with genetic approaches in C. elegans and a recently developed transgenic circadian reporter to investigate the mechanisms underlying temperature-entrainment of the clock(s).
Aim 1 will develop a real-time automated imaging system for long-term recording and quantification of circadian rhythms in gene expression in C. elegans induced by temperature cycles. This new in vivo automated imaging system will be useful for studying temperature-entrained rhythms in genetic mutants and strains defective in perception and transduction of temperature signals in C. elegans. The automated system will also allow to genetically screen and isolate new mutations in genes that change temperature-entrained circadian rhythms.
Aim 2 will define and characterize the molecular components of the temperature-entrained clock(s). These components are expected to be coding for clock genes and components that process temperature information to the clock(s). We will use advanced whole-genome re-sequencing approaches to identify these molecular components. This genetic model organism provides an attractive new avenue for understanding the circadian clock, and it is possible that homologs of new genes identified in C. elegans that are necessary for temperature-entrainment of this clock may function in higher organisms.
This proposal will address the genetic and neurobiological basis of temperature-entrained circadian rhythms. Understanding the inner workings of the circadian clock in great depth and the impacts on circadian time keeping is crucial in better understanding circadian rhythm disruptions, such as changes in natural body temperature cycles, commonly found in patients with neurological disorders, such as stroke.
|Winbush, Ari; Gruner, Matthew; Hennig, Grant W et al. (2015) Long-term imaging of circadian locomotor rhythms of a freely crawling C. elegans population. J Neurosci Methods 249:66-74|