Circadian Biology Research Articles

Bridging the gap: examining circadian biology and fatigue alongside work schedules

We compared three different work schedules in a large oil company: 1) two days of 12 h of daytime shifts followed by two consecutive 12 h night shifts, followed by four work-free days (“2 x 2 x 4”), 2) four consecutive 12 h daytime shifts and four consecutive 12 h night shifts, flanked by four work-free days (“4 x 4 x 4”), 3) a non-rotating schedule involving continuous 12 h daytime shifts during 40 days (“fixed 12 h”). We measured wrist-actigraphy, peripheral temperature rhythms, and subjective self-reports regarding fatigue, somnolence, and psycho-affective features. Sleep duration on the resting period was significantly less than the recommended 7 h. The “2 x 2 x 4” schedule resulted in decreased sleep regularity and increased circadian disruption, higher levels of insomnia, increased fatigue impact, lower alertness levels, and heightened symptoms of depression associated with more nocturnal sleep time after diurnal work. Our findings indicate that health and safety vary depending on the type of schedule employed.

Hierarchy or Heterarchy of Mammalian Circadian Timekeepers?

Mammalian circadian biologists commonly characterize the relation between circadian clocks as hierarchical, with the clock in the suprachiasmatic nucleus at the top of the hierarchy. The lineage of research since the suprachiasmatic nucleus (SCN) was first identified as the clock in mammals has challenged this perspective, revealing clocks in peripheral tissues, showing that they respond to their own zeitgebers, coordinate oscillations among themselves, and in some cases modify the behavior of the SCN. Increasingly circadian timekeepers appear to constitute a heterarchical network, with control distributed and operating along multiple pathways. One reason for the continued invocation of hierarchy in mammalian circadian biology is that it is difficult to understand how a heterarchical system could operate effectively so as to maintain the organism. Evolved mechanisms, however, need not respect hierarchy and those that have survived have demonstrated the ability of heterarchical organizaton to maintain organisms.

Differential Effects of Light and Dark Phase Modifications on Jet Lag Adaptability in Mice

ABSTRACTIn chronobiology, shifting light/dark cycles is a common method to disrupt circadian rhythms. While the direction and magnitude of a phase shift (e.g., +6 denoting a 6‐h advanced shift) dictate the temporal change before and after the shift, little attention has been paid to the duration and relative proportion of daytime and nighttime during the shift, leading to a critical, unexamined variable in circadian research. In this study, we introduce the concepts of “L‐shift” (longer light phase on the shift day) and “D‐shift” (longer dark phase), and investigate how these variations impact the adaptability of mice to jet lag. By examining multiple phase shifts (12L vs. 12D, +6L vs. +6D, −6L vs. −6D), we demonstrate that L‐shifts not only facilitate faster adaptation but also significantly reduce the severity of sepsis in a jet lag‐sensitive lipopolysaccharide‐induced sepsis model. Further investigations with additional phase shifts at 1‐h intervals (+8 to +11) reinforced the enhanced fitness of mice under L‐shifts. Mechanistically, L‐shifts were found to increase sleep duration, thereby improving circadian entrainment, with sleep deprivation nullifying the adaptability differences between lighting protocols. These findings underscore a previously unrecognized factor in circadian biology and suggest that optimizing lighting protocols could profoundly improve adaptability to circadian disruptions. This research opens new avenues for enhancing therapeutic strategies and refining experimental designs in the field of chronobiology.

Hypertension disrupts the vascular clock in both sexes.

Blood pressure (BP) displays a circadian rhythm and disruptions in this pattern elevate cardiovascular risk. Although both central and peripheral clock genes are implicated in these processes, the importance of vascular clock genes is not fully understood. BP, vascular reactivity, and the renin-angiotensin-aldosterone system display overt sex differences, but whether changes in circadian patterns underlie these differences is unknown. Therefore, we hypothesized that circadian rhythms and vascular clock genes would differ across sex and would be blunted by angiotensin II (ANG II)-induced hypertension. ANG II infusion elevated BP and disrupted circadian patterns similarly in both males and females. In females, an impact on heart rate (HR) and locomotor activity was revealed, whereas in males hypertension suppressed baroreflex sensitivity (BRS). A marked disruption in the vascular expression patterns of period circadian regulator 1 (Per1) and brain and muscle aryl hydrocarbon receptor nuclear translocator like protein 1 (Bmal1) was noted in both sexes. Vascular expression of the G protein-coupled estrogen receptor (Gper1) also showed diurnal synchronization in both sexes that was similar to that of Per1 and Per2 and disrupted by hypertension. In contrast, vascular expression of estrogen receptor 1 (Esr1) showed a diurnal rhythm and hypertension-induced disruption only in females. This study shows a strikingly similar impact of hypertension on BP rhythmicity, vascular clock genes, and vascular estrogen receptor expression in both sexes. We identified a greater impact of hypertension on locomotor activity and heart rate in females and on baroreflex sensitivity in males and also revealed a diurnal regulation of vascular estrogen receptors. These insights highlight the intricate ties between circadian biology, sex differences, and cardiovascular regulation.NEW & NOTEWORTHY This study reveals that ANG II-induced hypertension disrupts the circadian rhythm of blood pressure in both male and female mice, with parallel effects on vascular clock gene and estrogen receptor diurnal patterns. Notably, sex-specific responses to hypertension in terms of locomotor activity, heart rate, and baroreflex sensitivity are revealed. These findings pave the way for chronotherapeutic strategies tailored to mitigate cardiovascular risks associated with disrupted circadian rhythms in hypertension.

Adipocyte sphingosine kinase 1 regulates histone modifiers to disrupt circadian function.

Circadian rhythms align biological functions with the 24-hour day-night cycle, but modern artificial light disrupts these patterns, contributing to health issues like obesity and cardiovascular disease. The circadian clock operates through a transcriptional-translational feedback loop involving core components such as BMAL1 and CLOCK. Recent research has shown circadian variations in sphingolipid metabolism, specifically sphingosine-1-phosphate (S1P), which plays crucial signaling roles. This study investigates the sphingolipid enzyme, sphingosine kinase 1 (SphK1), which converts sphingosine to S1P, as a circadian-regulated gene in adipocytes. We find that SphK1 expression and activity follow a circadian rhythm, regulated by BMAL1 and CLOCK binding to its promoter. Adipocyte-specific SphK1 knockout mice exhibit disrupted circadian rhythms, and impaired adipocyte function. Additionally, SphK1 deficiency leads to reduced histone acetylation and altered histone deacetylase (HDAC) localization, affecting gene regulation. These results highlight the critical role of SphK1 in linking lipid metabolism with circadian biology.

Machine learning reveals the transcriptional regulatory network and circadian dynamics of Synechococcus elongatus PCC 7942

Synechococcus elongatus is an important cyanobacterium that serves as a versatile and robust model for studying circadian biology and photosynthetic metabolism. Its transcriptional regulatory network (TRN) is of fundamental interest, as it orchestrates the cell's adaptation to the environment, including its response to sunlight. Despite the previous characterization of constituent parts of the S. elongatus TRN, a comprehensive layout of its topology remains to be established. Here, we decomposed a compendium of 300 high-quality RNA sequencing datasets of the model strain PCC 7942 using independent component analysis. We obtained 57 independently modulated gene sets, or iModulons, that explain 67% of the variance in the transcriptional response and 1) accurately reflect the activity of known transcriptional regulations, 2) capture functional components of photosynthesis, 3) provide hypotheses for regulon structures and functional annotations of poorly characterized genes, and 4) describe the transcriptional shifts under dynamic light conditions. This transcriptome-wide analysis of S. elongatus provides a quantitative reconstruction of the TRN and presents a knowledge base that can guide future investigations. Our systems-level analysis also provides a global TRN structure for S. elongatus PCC 7942.

Photoneuroendocrine, circadian and seasonal systems: from photoneuroendocrinology to circadian biology and medicine.

This contribution highlights the scientific development of two intertwined disciplines, photoneuroendocrinology and circadian biology. Photoneuroendocrinology has focused on nonvisual photoreceptors that translate light stimuli into neuroendocrine signals and serve rhythm entrainment. Nonvisual photoreceptors first described in the pineal complex and brain of nonmammalian species are luminance detectors. In the pineal, they control the formation of melatonin, the highly conserved hormone of darkness which is synthesized night by night. Pinealocytes endowed with both photoreceptive and neuroendocrine capacities function as "photoneuroendocrine cells." In adult mammals, nonvisual photoreceptors controlling pineal melatonin biosynthesis and pupillary reflexes are absent from the pineal and brain and occur only in the inner layer of the retina. Encephalic photoreceptors regulate seasonal rhythms, such as the reproductive cycle. They are concentrated in circumventricular organs, the lateral septal organ and the paraventricular organ, and represent cerebrospinal fluid contacting neurons. Nonvisual photoreceptors employ different photopigments such as melanopsin, pinopsin, parapinopsin, neuropsin, and vertebrate ancient opsin. After identification of clock genes and molecular clockwork, circadian biology became cutting-edge research with a focus on rhythm generation. Molecular clockworks tick in every nucleated cell and, as shown in mammals, they drive the expression of more than 3000 genes and are of overall importance for regulation of cell proliferation and metabolism. The mammalian circadian system is hierarchically organized; the central rhythm generator is located in the suprachiasmatic nuclei which entrain peripheral circadian oscillators via multiple neuronal and neuroendocrine pathways. Disrupted molecular clockworks may cause various diseases, and investigations of this interplay will establish a new discipline: circadian medicine.

Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment.

Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

Characterization of Chronotypes Using the Symbolic Aggregate apprXimation (SAX) on Actigraphy Data.

In this study, we discuss an efficient approach to characterizing chronotypes using Symbolic Aggregate approXimation (SAX) on actigraphy data. Actigraphy, a non-invasive monitoring of human rest/activity cycles, provides valuable insights into sleep-wake behaviors and circadian rhythms. However, the high dimensionality of actigraphy data poses significant challenges in storage, processing, and analysis. To address these challenges, we applied the SAX algorithm to transform continuous time-series actigraphy data into a symbolic representation, enabling dimensionality reduction while preserving essential patterns. We analyzed actigraphy data from the National Health and Nutrition Examination Survey (NHANES) database, covering over 10,000 individuals, and used unsupervised clustering to identify distinct chronotype patterns. The SAX transformation facilitated the application of machine learning techniques, revealing five chronotype clusters characterized by differences in activity onset, resolution, and intensity. Age distribution analysis showed biases towards specific age groups within the clusters, highlighting the relationship between age and chronotype. Key findings include age-related Chronotype variations with younger individuals exhibiting delayed chronotypes with significant differences in sleep onset (SOT) and wake time (WT) compared to older adults, suggesting a phase delay in sleep patterns as age decreases and activity transition dynamics where clusters showed distinct patterns in winding up and winding down periods, providing insights into the dynamics of activity transitions. This study demonstrates the efficiency and effectiveness of SAX in processing large-scale actigraphy data, enabling robust chronotype characterization that can inform personalized healthcare and public health initiatives. Further exploration of SAX integration with other biometric measures could deepen our understanding of human circadian biology and its impact on health and behavior.

Analysis of Circadian Clock Gene Expression in Human Skin Explants

Many aspects of skin biochemistry and physiology are known to vary over the course of the 24-hour day. Traditional approaches to study circadian rhythms in the skin have employed rodents or human subjects, which limit the experimental variables that can be studied. Although explants derived from discarded surgical skin are a commonly used model in the skin biology field, circadian rhythms have yet to be examined exvivo. In this study, using human panniculectomy skin, we used RT-qPCR to monitor the epidermal expression of 4 core circadian clock genes over the course of 1 day exvivo. Although significant interindividual variability in overall gene expression profiles was observed, robust circadian oscillations were observed in many of the genes and individual explants. Comparison of our gene expression data with microarray data from 2 previous human-subject studies involving primarily young adult White males revealed both similarities and differences, including greater distribution in the time of day of peak expression in the skin explants. This increased variability appears to be due in part to the increased age and altered sex distribution of the donated skin. Nonetheless, our results indicate that skin explants offer an additional experimental system for studying circadian skin biology.

Rhythmidia: A modern tool for circadian period analysis of filamentous fungi.

Circadian rhythms are ubiquitous across the kingdoms of life and serve important roles in regulating physiology and behavior at many levels. These rhythms occur in ~24-hour cycles and are driven by a core molecular oscillator. Circadian timekeeping enables organisms to anticipate daily changes by timing their growth and internal processes. Neurospora crassa is a model organism with a long history in circadian biology, having conserved eukaryotic clock properties and observable circadian phenotypes. A core approach for measuring circadian function in Neurospora is to follow daily oscillations in the direction of growth and spore formation along a thin glass tube (race tube). While leveraging robust phenotypic readouts is useful, interpreting the outputs of large-scale race tube experiments by hand can be time-consuming and prone to human error. To provide the field with an efficient tool for analyzing race tubes, we present Rhythmidia, a graphical user interface (GUI) tool written in Python for calculating circadian periods and growth rates of Neurospora. Rhythmidia is open source, has been benchmarked against the current state-of-the-art, and is easily accessible on GitHub.

The pathophysiology of estrogen in perinatal depression: conceptual update.

Estrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD? A literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions. Estrogen fluctuations must be conceptualized in the context of multiple dramatic and interacting changes inherent in pregnancy and after birth, including progesterone, corticosteroids, inflammation, circadian biology and psychosocial challenges. Individuals who develop PPD have increased sensitivity to epigenetic alteration at estrogen-responsive genes, and these changes are highly predictive of PPD. An effective estrogen-based treatment for PPD has yet to be found, but interventions focused on associated inflammation and circadian rhythms are promising. Our understanding of the biological basis of PPD, one of the most common morbidities of the perinatal period, is expanding beyond changes in gynecologic hormone concentrations to include their impact on other systems. This growing understanding of the many processes influencing PPD will allow for the development of novel prevention and treatment strategies.

Day-night gene expression reveals circadian gene disco as a candidate for diel-niche evolution in moths.

Temporal ecological niche partitioning is an underappreciated driver of speciation. While insects have long been models for circadian biology, the genes and circuits that allow adaptive changes in diel-niches remain poorly understood. We compared gene expression in closely related day- and night-active non-model wild silk moths, with otherwise similar ecologies. Using an ortholog-based pipeline to compare RNA-Seq patterns across two moth species, we find over 25 pairs of gene orthologs showing differential expression. Notably, the gene disco, involved in circadian control, optic lobe and clock neuron development in Drosophila, shows robust adult circadian mRNA cycling in moth heads. Disco is highly conserved in moths and has additional zinc-finger domains with specific nocturnal and diurnal mutations. We propose disco as a candidate gene for the diversification of temporal diel-niche in moths.

Circadian Clock Gene Dysregulation in Alzheimer’s Disease: Insights and Implications

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is increasingly understood to involve not just traditional neuropathological hallmarks but also disruptions in systemic physiological processes, notably the circadian rhythms. The intersection of circadian clock gene dysregulation and the pathogenesis of AD, emphasizing both the insights gained and the potential therapeutic implications. Circadian rhythms, which govern daily physiological and metabolic processes, are regulated by core clock genes such as BMAL1, PER, CRY, and others. In AD, multiple studies have observed altered expression and function of these genes, which may contribute to the characteristic symptoms of the disease, including disrupted sleep patterns, changes in daily activity levels, and mood fluctuations. circadian dysfunction might exacerbate AD pathology through mechanisms such as increased amyloid-beta production, impaired clearance, and neuroinflammation. Furthermore, targeting circadian clock genes and their regulatory pathways might offer novel strategies for AD management, such as the timing of drug administration to coincide with optimal circadian phases, or the use of chronotherapeutics. Finally, identifing gaps in current knowledge and suggests directions for future research to better understand the role of circadian biology in AD and to harness this information for therapeutic benefit. This review not only underscores the importance of circadian rhythms in AD but also highlights the potential for circadian-based interventions to mitigate disease progression and improve quality of life for affected individuals.

Crosstalk between circadian clocks and pathogen niche.

Circadian rhythms are intrinsic 24-hour oscillations found in nearly all life forms. They orchestrate key physiological and behavioral processes, allowing anticipation and response to daily environmental changes. These rhythms manifest across entire organisms, in various organs, and through intricate molecular feedback loops that govern cellular oscillations. Recent studies describe circadian regulation of pathogens, including parasites, bacteria, viruses, and fungi, some of which have their own circadian rhythms while others are influenced by the rhythmic environment of hosts. Pathogens target specific tissues and organs within the host to optimize their replication. Diverse cellular compositions and the interplay among various cell types create unique microenvironments in different tissues, and distinctive organs have unique circadian biology. Hence, residing pathogens are exposed to cyclic conditions, which can profoundly impact host-pathogen interactions. This review explores the influence of circadian rhythms and mammalian tissue-specific interactions on the dynamics of pathogen-host relationships. Overall, this demonstrates the intricate interplay between the body's internal timekeeping system and its susceptibility to pathogens, which has implications for the future of infectious disease research and treatment.

Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology.

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

An Update on the Role of Circadian Rhythms in Sleep Disorders

Background: The comprehension of the molecular, cellular, and biological mechanisms that underlie the management of the sleep-wake cycle, as well as the effects of circadian disruption on health and illness, has made significant strides. Methods: An extensive literature review was done from the standard databases such as Scopus, Elsevier, and PubMed using standard keywords “Circadian rhythm”, and “sleep disorders”. In this section, we examined circadian biology and provided adetailed description of the pathogenesis, clinical characteristics, diagnosis, and management of the most typical Circadian rhythm sleep disorders (CRSDs) seen in clinical practice. Conclusion: It can be concluded that the central circadian rhythm mechanism may be altered, or the intrinsic circadian clock and the environment may not be in sync, to produce circadian rhythm sleep disorders. As a consequence, we must focus on modifying our way of life in a constructive and healthy way. Even while the lifestyle is based on personal preferences and identities, it is important to examine it in isolation from its sociocultural environment.

Methods to estimate body temperature and energy expenditure dynamics in fed and fasted laboratory mice: effects of sleep deprivation and light exposure

Monitoring body temperature and energy expenditure in freely-moving laboratory mice remains a powerful methodology used widely across a variety of disciplines–including circadian biology, sleep research, metabolic phenotyping, and the study of body temperature regulation. Some of the most pronounced changes in body temperature are observed when small heterothermic species reduce their body temperature during daily torpor. Daily torpor is an energy saving strategy characterized by dramatic reductions in body temperature employed by mice and other species when challenged to meet energetic demands. Typical measurements used to describe daily torpor are the measurement of core body temperature and energy expenditure. These approaches can have drawbacks and developing alternatives for these techniques provides options that can be beneficial both from an animal-welfare and study-complexity perspective. First, this paper presents and assesses a method to estimate core body temperature based on measurements of subcutaneous body temperature, and second, a separate approach to better estimate energy expenditure during daily torpor based on core body temperature. Third, the effects of light exposure during the habitual dark phase and sleep deprivation during the light period on body temperature dynamics were tested preliminary in fed and fasted mice. Together, the here-published approaches and datasets can be used in the future to assess body temperature and metabolism in freely-moving laboratory mice.

The International Master of Advanced Studies (MAS) in Sleep Medicine of the Universities of Bern and Svizzera Italiana

Introduction: Sleep–wake circadian disorders (SWCDs) are very frequent and linked to major negative effects on the body, mental health, the brain, and on occupational and societal health. The prevention, diagnosis, and treatment of SWCDs and the promotion of sleep health require the sufficient education of general practitioners, specialists, and other health professionals. Unfortunately, education at pre- and postgraduate level is insufficient in most countries across the world. Aims and methods: This article describes the historical context, basic considerations, and methodological approach for the creation of the International Postgraduate Sleep Master by the University of Bern and Svizzera Italiana. Results: The postgraduate Master, which was launched in 2017, is a part-time, flexible course, taken over 2 ½ years, which targets health professionals, scientists, and technicians. After an initial introduction, which is the same for everybody (“common trunk”), the course can be individualized. The 12 modules of the Master include online lectures, schools, internships in a sleep center (in one of our 15 partner universities), case discussions and interactive sessions with students and internationally recognized experts from over 20 countries across the world, and culminates with a Master thesis. The program covers sleep–wake circadian biology; the management of SWCDs; disturbances of consciousness and sleep-related epilepsies; novel approaches in sleep medicine (e.g., clinical trials, telemedicine, data science, artificial intelligence); and topics of increasing relevance (e.g., neurodegenerative disorders, gender and diversity, sleep health, new technologies, artificial intelligence, professional and societal implications). Students are encouraged to also take “crash courses” in preparation for the national, European, and World sleep examinations. Conclusion: The Postgraduate University Sleep Master of the Universities of Bern and Svizzera Italiana offers a unique part-time, (mainly) virtual opportunity to acquire state-of the art knowledge, skills, and professional experiences to prepare for a clinical or scientific career in sleep medicine for physicians, scientists, and other health professionals.

Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.