Profiles

Alexander van der Linden, Ph.D.

Postdoctoral Fellow

Ph.D., University of Utrecht, Netherlands

slinden [at] brandeis.edu

Circadian Rhythms of C. elegans

The circadian clock is an internal timing mechanism that enables organisms to respond to, and even anticipate changing environmental conditions associated with rotation of the earth. The output of these clocks results in circadian rhythms, which oscillate with circa 24 hr periods and control multiple aspects of behavior and physiology. These include the regulation of the daily timing of sleep/wake cycles, feeding and locomotory behavior as well as multiple physiological and metabolic processes. Disruption of the timing of these processes can lead to severe metabolic and behavioral disorders, including sleep dysfunction, obesity and even cancer. Thus, a complete understanding of the mechanisms that underlie circadian rhythms is highly relevant to human health and quality of life.

Circadian rhythms can be entrained by daily environmental signals (zeitgebers) such as light/dark and temperature. Following entrainment, circadian rhythms persist for days, weeks, and even months under free-running conditions. In depth genetic and genomic analyses have identified the molecular mechanisms comprising these clocks in most model organisms studied such as cyanobacteria, Neurospora, Arabidopsis, Drosophila and mouse, and it has been shown that while some molecules are conserved, other clocks are driven by highly divergent mechanisms. Current models of these clocks revolve around transcriptional/post-translational feed-back loops, in which clock proteins negatively regulate their cognate clock genes. More recently, a whole new level of circadian feedback regulation was revealed, implicating post-transcriptional regulatory miRNAs in the control of the circadian clock.

Surprisingly, the circadian clock in the model organism C. elegans remains uncertain and certainly uncharacterized. C. elegans exhibits circadian rhythms in locomotory behavior and hyperosmotic stress following light/dark entrainments, but the clock genes involved are unknown. Homologs of clock genes are represented in the genome of C. elegans, but their only certain function is to regulate developmental timing. Thus, whether C. elegans has a bona fide circadian clock remains an open question.

I am interested in determining whether C. elegans possesses a circadian clock, and in identifying the underlying components and molecular mechanisms.

I use expression profilling to identify transcripts that cycle in a circadian manner in C. elegans after light/dark and temperature entrainment. It’s my hope to identify candidate clock and clock-output genes, and examine the spatial and temporal expression pattern of these candidate genes using in vivo reporters. Using these reporters, I hope to identify the sensory cells and pathways required for light/dark and temperature entrainment of the C. elegans clock.

This work is being done in collaboration with Michael Rosbash (Brandeis University).

Sengupta Lab Publications

van der Linden, A.M., Wiener, S., You, Y-J., Kim, K., Avery L., and Sengupta, P. (2008) The EGL-4 PKG acts with the KIN-29 SIK and KIN-2 PKA to regulate chemoreceptor gene expression and sensory behaviors in C. elegans. Genetics. In Press. [PubMed]

van der Linden, A.M., Nolan, K.M., and Sengupta, P. (2007). KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC. EMBO J 26, 358-370. [PubMed]