Highlights d B. subtilis PXN21 inhibits and reverses a-syn aggregation in a C. elegans model d Spores and vegetative cells protect through different mechanisms d The probiotic inhibits a-syn aggregation by changing the host sphingolipid metabolism d Biofilm formation in the gut and bacterial metabolites reduce a-syn aggregation
Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems-including mice, flies, fungi, plants, and bacteria-have provided important insights into the mechanisms of circadian rhythmicity. However, the general principles that govern the circadian clock of Caenorhabditis elegans have remained largely elusive. Here we report robust molecular circadian rhythms in C. elegans recorded with a bioluminescence assay in vivo and demonstrate the main features of the circadian system of the nematode. By constructing a luciferase-based reporter coupled to the promoter of the suppressor of activated let-60 Ras (sur-5) gene, we show in both population and single-nematode assays that C. elegans expresses ∼24-h rhythms that can be entrained by light/dark and temperature cycles. We provide evidence that these rhythms are temperature-compensated and can be re-entrained after phase changes of the synchronizing agents.In addition, we demonstrate that light and temperature sensing requires the photoreceptors LITE and GUR-3, and the cyclic nucleotidegated channel subunit TAX-2. Our results shed light on C. elegans circadian biology and demonstrate evolutionarily conserved features in the circadian system of the nematode.C. elegans | circadian rhythms | luminescence | temperature | light
Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.
Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms, ranging from bacteria to fungi, plants, and animals. Circadian rhythms are generated by endogenous clocks that can be entrained daily by environmental cycles such as light and temperature. The molecular machinery of circadian clocks includes a transcriptional-translational feedback loop that takes approximately 24 h to complete. Drosophila melanogaster has been a model organism of choice to understand the molecular basis of circadian clocks. However, alternative animal models are also being adopted, each offering their respective experimental advantages. The nematode Caenorhabditis elegans provides an excellent model for genetics and neuro-behavioral studies, which thanks to its ease of use and manipulation, as well as availability of genetic data and mutant strains, is currently used as a novel model for circadian research. Here, we aim to evaluate C. elegans as a model for chronobiological studies, focusing on its strengths and weaknesses while reviewing the available literature. Possible zeitgebers (including light and temperature) are also discussed. Determining the molecular bases and the neural circuitry involved in the central pacemaker of the C. elegans’ clock will contribute to the understanding of its circadian system, becoming a novel model organism for the study of diseases due to alterations of the circadian cycle.
Circadian rhythms are endogenous oscillations present in nearly all organisms from prokaryotes to humans, allowing them to adapt to cyclical environments close to 24 hours. Circadian rhythms are regulated by a central clock, which is based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematodeCaenorhabditis elegans,periodandcasein kinase 1ε/δare conserved aslin-42andkin-20, respectively. Here we studied the involvement oflin-42andkin-20in circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations oflin-42andkin-20generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and seam cells, a population of epidermal stem cells inC. elegansthat undergo multiple divisions during development. Depletion of LIN-42 and KIN-20 specifically in neuronal cells after development was sufficient to lengthen the period of oscillatingsur-5expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.
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