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2017 Nobel Prize in Physiology or Medicine

The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their elucidation of the molecular mechanisms controlling circadian rhythm.  Their pioneering work in Drosophila uncovered the internal oscillators, or clocks, that synchronise cellular metabolism and organismal behaviour to the light/dark cycle to generate biological rhythms with 24 hour periodicity.
 

From the winners

Most animal cells, even in tissue cultures, can develop the molecular oscillations underlying circadian rhythms. To harness this property into the complex time-related behavioural patterns seen in whole organisms requires the intervention of a series of individual brain oscillators. Drosophila is proving to be a good model in which to study this system. The flies manifest characteristic morning and evening locomotor activity, each controlled by a different group of adult brain clock neurons. Now, by generating transgenic animals with different circadian periods in these morning and evening cells, the brain clock cells are shown to be organized into two separate neuronal circuits. One circuit includes the morning and evening cells and drives circadian locomotor activity. The timing of the evening cells is determined by the morning cells as a result of a daily resetting signal from the morning to the evening cells, which then run at their genetically programmed pace between signals.

Letter | | Nature

News and Comments

Plants contain several tissue-specific decentralized but communicating ‘clocks’. These control developmental outputs in response to environmental change: the vasculature clock for photoperiodic control of flowering, and the epidermis clock for temperature-dependent elongation.

News & Views | | Nature Plants

Master circadian clocks in discrete neurons trigger profound daily changes in brain states, such as sleep and wake states. A study now finds a circuit through which these pacemakers act to control daily behavioral rhythms in Drosophila.

News & Views | | Nature Neuroscience

Many aspects of sleep, including the how and why, are still mysterious, especially its relationship to learning and memory. A new study suggests that sleep may serve to reset synaptic potentiation, linking it to homeostatic plasticity.

News & Views | | Nature Neuroscience

The Per2 gene is a core component of the circadian clock in mammals. It now seems that the mouse Per2 gene is also involved in suppressing tumours, through other genes that affect cell proliferation and death.

News & Views | | Nature

Circadian regulation of epigenetic chromatin marks drives daily transcriptional oscillation of thousands of genes and is intimately linked to cellular metabolism and bioenergetics. New work links circadian fluctuations in the activity of the SIRT1 deacetylase, a sensor of the cellular energy state, to histone-methylation changes and the circadian expression of clock-controlled genes.

News & Views | | Nature Structural & Molecular Biology

Research

The effect of the liver clock is modified by food entrainment via Bmal1/Clock core machinery. Here the authors show that insulin promotes postprandial Akt-dependent phosphorylation of Bmal1, resulting in association with 14-3-3 and Bmal1 shuttling out of the nucleus, thereby disrupting Bmal1 transcriptional effects on the clock.

Article | open | | Nature Communications

This study finds that mice's biological clocks are permanently influenced by the seasonal photoperiod at and after birth. In mice raised under summer-like light periods, rhythmic gene expression in the suprachiasmatic nucleus was tightly correlated with lights-off under both summer- and winter-like cycles. In 'winter-born' mice, these rhythms were tightly correlated only under winter-like light cycles.

Brief Communication | | Nature Neuroscience

Circadian rhythms and related behaviours vary across individuals. Here, a large genome-wide association study reveals common single nucleotide variants influencing whether an individual reports as being a ‘morning person’ by identifying 15 significant loci, including 7 near known circadian genes.

Article | open | | Nature Communications

New data show that Clock–Bmal1, the central transcriptional activator that drives expression of circadian target genes, also recruits the Ddb1–Cullin-4 ubiquitin ligase to clock promoters to enhance the subsequent binding of the feedback repressors that generate the circadian periodicity of gene expression.

Article | | Nature Structural & Molecular Biology

Reviews

Clock proteins are controlled by multiple post-translational modifications during the circadian cycle. In this Review, the authors examine how post-translational modifications influence the stability, interactions and activity of mammalian clock proteins and how they contribute to proper clock function or are altered in circadian disorders.

Review Article | | Nature Structural & Molecular Biology

Circadian rhythms are well established as having an important role in human biology. In this Review, circadian biology is presented in reference to the regulation of rheumatoid arthritis and the potential for chronotherapeutic intervention.

Review Article | | Nature Reviews Rheumatology

Evidence indicates that the disruption of the circadian clock might be directly linked to cancer. As described here, alterations in clock function could lead to aberrant cellular proliferation, DNA damage responses and altered metabolism.

Review Article | | Nature Reviews Cancer

Disruption of circadian rhythms in neurodegenerative disorders not only contributes to morbidity and poor quality of life, but could also be involved in driving the disease process itself. Restoration of circadian rhythmicity via behavioural or pharmacological interventions might, therefore, slow down disease progression. In this Review, Videnovic and colleagues provide an overview of the circadian system, and summarize current understanding of the dysfunction of circadian rhythms in Alzheimer disease, Parkinson disease and Huntington disease.

Review Article | | Nature Reviews Neurology

Adequate circadian oscillation of endocrine factors is essential in the maintenance of metabolic homeostasis. The authors of this Review explain the influence of extrinsic and intrinsic factors on endocrine circadian rhythms and how dysregulation of these rhythms can lead to disease in animals and humans. They also discuss therapeutic strategies to restore circadian rhythmicity and improve metabolism.

Review Article | | Nature Reviews Endocrinology