Keynote Speakers

Frank Scheer

Professor of Medicine, Harvard Medical School (HMS)

Director, Medical Chronobiology Program, Brigham and Women’s Hospital (BWH)

Senior Neuroscientist, Departments of Medicine and Neurology, BWH

Chrononutrition to Optimize Health

Abstract

Nutrition, sleep, physical activity, metabolism, and circadian rhythms are tightly intertwined and have an important impact on health and disease. There is convincing evidence that uncoupling their timing, e.g., occurring during shift work, light at night, or inverted activity rhythms, has adverse health consequences. Recent findings indicate that the normalization of the eating rhythm, by itself, can decrease or even prevent these adverse health consequences. These insights have ignited broad interest in the potency of chrononutrition to improve health.

In this keynote, I will present evidence for the role of the endogenous circadian system in regulating various aspects of metabolism, including glucoregulation, energy expenditure, and energy intake; will provide examples of the impact of circadian misalignment on cardiometabolic risk, mood, and inflammatory markers; will present findings on the influence of diurnal and circadian food timing on metabolism and their relationship with obesity and weight loss success; and will discuss the promise for leveraging chrononutrition for optimizing health, in the general population and in individuals experiencing circadian misalignment such as shift workers.

Biography

Frank A.J.L. Scheer, PhD, MSc, is a Professor of Medicine at Harvard Medical School (HMS), Senior Neuroscientist at Brigham and Women's Hospital (BWH), and the Director of the Medical Chronobiology Program (MCP) at BWH, Boston. Dr. Scheer co-founded and currently directs the MCP, an interdisciplinary research program at BWH to foster the translational research in sleep and circadian biology to understand the basis behind time-variant changes in disease severity, the effects of circadian misalignment (typical in night shift workers), food timing, and their interaction with genetics (e.g., the common MTNR1B variant).

Understanding the biological basis of these changes across the day and night and their interaction with genetics may help in the development of personalized and time-based behavioral, environmental, and pharmaceutical interventions (e.g., appropriately timed meals, exercise, light, or melatonin to target specific phases of the body clock) to prevent, treat, and/or manage disease.

Since 2005, Dr. Scheer has been funded continuously as Principal Investigator by the National Institutes of Health (NIH). Dr. Scheer has been the Founding Chair of the Communications Committee, a member of the Program Committee, and faculty member of the Professional Development Committee of the Society of Research on Biological Rhythms (SRBR); a member of the Board of Directors and the Program Committee of the European Biological Rhythms Society (EBRS); and a member of many committees within the Sleep Research Society (SRS), including of the Program Committee, the Awards Nominating Committee, and of the Board of Directors.

He is an Editorial Board Member of several peer-reviewed journals, and an Associate Editor of the journals SLEEP and Frontiers in Sleep. Dr. Scheer has received numerous scientific awards, including the Neal Miller Award by the Academy of Behavioral Medicine Research, the Pillars of Excellence Award by Mass General Brigham; the Mrosovsky Keynote Lecture Award by the Canadian Society for Chronobiology, and the Outstanding Scientific Achievement Award by the Sleep Research Society.

Valérie Simonneaux

Co-directrice d'équipe Régulation et Perturbation des Rythmes Neuroendocriniens

Institut des Neurosciences Cellulaires et Intégratives

CNRS UPR-3212, Strasbourg

Neuroendocrine mechanisms of seasonal adaptation and maladaptation

Abstract

Annual changes in environmental factors had led organisms to develop adaptive biological and behavioural strategies. In mammals, the seasonal change in the nocturnal production of the pineal hormone melatonin is pivotal for metabolic and reproductive adaptations.

The discovery that melatonin acts on the pars tuberalis to control the synthesis of TSH, which in turn acts on the hypothalamic tanycytes to modulate local thyroid hormone metabolism, has been a breakthrough in our understanding of the neuroendocrine mechanisms underlying seasonal adaptation. In this lecture, I will discuss how this melatonin/thyroid hormone signal regulates hypothalamic circuits to synchronize physiological functions with the seasons. I will also report how exposure to environmental disruptors may affect seasonal adaptation.

Biography

Valérie Simonneaux is a CNRS director of research at the Institute of Cellular and Integrative Neurosciences in Strasbourg, France and leader of the team “Regulation and Disruption of Neuroendocrine Rhythms”. She also leads the Strasbourg’s Interdisciplinary Institute of Neuroscience of the University of Strasbourg.

She has a broad background in the neuroendocrinology of biological rhythms. She studies the mechanisms by which daily information (via neuroendocrine outputs of the circadian clock) and seasonal information (via melatonin) synchronize the cycles of reproduction and metabolic activity. In this respect, her work has demonstrated that hypothalamic peptides of the RF-amide family (kisspeptin and RFRP-3) are essential relays between temporal signals and the activity of GnRH neurons, and that hypothalamic tanycytes are involved in the long-term effect of thyroid control of seasonal functions (reproduction, maternal photoperiodic programming, hibernation). Currently, her work focuses more specifically on the study of environmental disturbances (light pollution, endocrine disruptors, metabolic diseases) on biological rhythms. These projects involve collaborations with national (Tours, Strasbourg) and international (Rabat, Tromso, South Africa) public research teams.

Besides her research activity, she teaches Chronobiology, Neuroendocrinology and Environmental Neurosciences to Master students, and she organizes an International ChronoSchool in Strasbourg.

Debra J. Skene

Professor of Neuroendocrinology

University of Surrey

Melatonin and Metabolomics: Tracking central and peripheral clock rhythms in humans

Abstract

The endogenous melatonin rhythm is routinely used as a phase marker of the light-entrainable circadian clock in the hypothalamic suprachiasmatic nuclei (SCN), providing important information about the human circadian timing system. For example, melatonin measurements have characterised the phase-shifting effects of light (phase response curve), the intrinsic human period (tau), spectral sensitivity of circadian photoreception and desynchrony between the environment, behaviour and circadian timing when working night shifts.

With the discovery of peripheral clocks, tracking their timing in humans has proved more challenging. Early work measured clock gene expression in human tissue that could easily be obtained such as white blood cells, buccal tissue, adipose tissue, hair, skin and muscle biopsies. More recently high-throughput transcriptomics of human tissue has significantly increased sensitivity and coverage of the transcriptome. However, tracking human peripheral clocks in organs involved in digestion and metabolism, such as the liver, pancreas and gut remains a challenge.

In this lecture I will discuss the potential of metabolic profiling (metabolomics), using targeted UPLC-MS/MS technology, to track human peripheral clock timing in entrained and misaligned conditions. Experiments showing time-of-day and circadian variation in the human metabolome, the effects of sleep deprivation, mistimed food and simulated shift work on metabolite rhythms will be presented. After 3 nights of working shifts, endogenous circadian rhythms of many plasma metabolites were misaligned from the central SCN clock timing (melatonin and cortisol) by ~8-12 h (internal desynchrony) likely reflecting the peripheral clocks’ response to cues driven by mistimed behaviours. Melatonin measurement combined with metabolic profiling will thus be useful to measure circadian misalignment in shift work and test management strategies. The ambulatory U-RHYTHM device offers a novel and practical way of measuring high-resolution melatonin and metabolite rhythms in real-life.

Biography

Debra J. Skene, PhD, FMedSci, is Professor of Neuroendocrinology in the Section of Chronobiology at the University of Surrey, UK. She has over 30 years of research experience studying the human circadian timing system and circadian rhythm sleep/wake disorders as experienced by blind people, shift workers and older people (> 240 peer-reviewed publications).

Currently her main focus is studying the mechanisms linking circadian clocks, sleep and metabolism in health, circadian disorders and metabolic diseases using liquid chromatography/mass spectrometry (LC/MS) metabolomics. Currently Professor Skene's research team is studying the links between human circadian clocks, sleep/wake and feeding/fasting in health, circadian disorders and metabolic diseases (shift workers, Type 2 diabetes, liver disease). Investigating the effect of time of day, circadian clock, sleep and food influences on the human metabolome using targeted LC-MS metabolomics is currently a major focus.

Professor Skene is past President of the European Biological Rhythms Society (EBRS) and past Vice-President (Basic) of the European Sleep Research Society (ESRS). She is a Royal Society Wolfson Research Merit Awardee, an inventor on two granted patents and was a Co-Director of Stockgrand Ltd and Surrey Assays Ltd.

Anries Kalsbeek

Professor of Experimental Endocrinology

University of Amsterdam

Netherlands Institute for Neuroscience

Discovering the Ins and Outs of the SCN based on its Prototypical Neurotransmitter Vasopressin

Abstract

This lecture will concentrate on the significance of the vasopressin neurons in the SCN for the functional output of the biological clock that is contained within it. The vasopressin-containing subpopulation is a characteristic feature of the SCN in many species, including humans. The activity of the vasopressin neurons in the SCN shows a pronounced daily variation in its activity that has also been demonstrated in human post-mortem brains.

In the early years, animal experiments revealed an important role for SCN-derived vasopressin as an output signal in the control of neuroendocrine day/night rhythms, such as that of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. More recently, studies using vasopressin receptor knockout animals highlighted its importance in the intrinsic synchrony of the SCN as well. Reducing vasopressin signaling within the SCN seems to reduce the robustness of the circadian clock and thereby facilitate resynchronization to a new L/D environment.

The remarkable correlation between a diminished presence of vasopressin in the SCN and a deterioration of sleep-wake rhythms during ageing and depression indicate that, also in humans, the vasopressin neurons contribute considerably to the rhythmic output of the SCN, but also highlight its potential as a target for therapeutic interventions.

Biography

Andries Kalsbeek is professor of Experimental Neuroendocrinology at the Department of Endocrinology and Metabolism at the Amsterdam UMC and leader of the Hypothalamic Integration Mechanisms group at the Netherlands Institute for Neuroscience (NIN), both in Amsterdam, The Netherlands.

He performed his Ph.D. work at the Netherlands Institute for Brain Research (NIBR, nowadays NIN) and received his Ph.D. in Neurobiology from the University of Amsterdam (supervisor Prof. D.F. Swaab). He completed postdoctoral training at the Université Louis Pasteur in Strasbourg (supervisor Prof. Paul Pevet) and the NIBR (supervisor Prof. Ruud Buijs).

Nowadays, his studies focus on the role of the hypothalamus in the control of energy metabolism, with an emphasis on glucose metabolism, hormonal rhythms, the central biological clock, and the autonomic nervous system. The most important scientific question throughout the years has been how circadian and metabolic (feedback) information is integrated in the hypothalamus and transferred onto the neuroendocrine and autonomic nervous system to modulate peripheral physiology.

His ultimate goal is to decipher the mechanisms involved in the circadian control of energy metabolism and understand how its perturbation results in pathologies like type 2 diabetes and obesity.

Ralf Stanewsky

Institute of Neuro- and Behavioral Biology

University of Münster

Circadian temporal organization of behaviour and its benefits in insects

Abstract

Circadian rhythms are prevalent on Earth and temporally organize behaviour and physiology of organisms to occur in species specific ‘temporal niches’. However, species differ in how strictly individuals are controlled by their circadian clock, suggesting that it may offer advantages to extend the temporal niche under certain circumstances, for example during stressful environmental conditions. In this lecture, I will discuss two insect species (the fruit fly Drosophila melanogaster and the red flour beetle Tribolium castaneum) as examples for tight and relaxed temporal niche control, respectively. A potential mechanism controlling temporal niche adherence involves the evolutionary capacitor and chaperon protein HSP90. Within a small subset of clock neurons in the fly brain, HSP90 mitigates inter-individual behavioural variation by regulating expression of the circadian neuropeptide Pigment Dispersing Factor (PDF), presumably restricting temporal niche extension to stressful environmental conditions.

Even though such temporal organization and circadian clocks in general are not essential for survival of an individual (at least under laboratory conditions), it is assumed that they contribute to the overall fitness of organisms. By applying a novel behavioural choice assay we could show that the fruit fly D. melanogaster actively chooses environmental conditions allowing it to live in a temporally organized manner. Flies become arrhythmic in constant light, and offering them the possibility to enter a dark area restored circadian rhythms. We show that this self-generated behavioural rhythmicity is correlated with an improvement of sleep quality, demonstrating a direct benefit for circadian clocks and temporal organisation.

Biography

Ralf Stanewsky is a Professor of Molecular Behavioural Genetics at the Institute of Neuro- and Behavioural Biology at the University of Münster, Germany. He graduated from the University of Cologne (Germany) where he also obtained his PhD. His subjects were genetics and the study of nuclear proteins, which led him to a gene influencing vision and courtship song behaviours in the fruit fly Drosophila melanogaster.

For his Postdoc he went to the lab of Jeffrey C Hall (Nobel Laureate 2017), at Brandeis University in Waltham, MA (USA) to study the fruit fly circadian clock. In collaboration with Patrick Emery (at the time postdoc with Michael Rosbash) he identified Cryptochrome as a key protein for light-synchronisation of the circadian clock in fruit flies.

He set up his own lab at the University of Regensburg in Bavaria (Germany) before obtaining a Full Professorship at Queen Mary College, University of London and later on moved to UCL. Since 2016 he is a Professor at the University of Münster, Germany, where he continues his studies on the circadian clock.

His research focuses on how the circadian clock is synchronized to natural light:dark and temperature cycles, and how clocks can maintain constant clock speed, despite increasing temperatures, a phenomenon known as temperature compensation. Recently he also developed an interest to investigate the ecological importance of circadian clocks, for example to which extent individuals are confined to their temporal niche.