The research in BioClock is organized in three clusters, each focusing on a different aspect of the biological clock and its place in the world around us. In Cluster 1, we address the societal relevance of the biological clock, focusing on promoting physical health and mental wellbeing as well as preventing disease in our 24-h society. In Cluster 2, we use our knowledge of the biological clock for the benefit of patients throughout the healthcare system. Taking a truly inclusive approach, in Cluster 3 we focus on the world around us by addressing the effects of light pollution on the biological clocks in plants and animals in both rural and urban areas in order to establish and implement strategies that protect biodiversity.
Cluster 1 – Clocks in Society
In Cluster 1, we will develop and test practical interventions designed to help us maintain a healthy biological clock throughout life. The breakthroughs in this cluster include developing innovative lighting strategies, activity- and diet-related lifestyle interventions, personalized work schedules, and education programmes designed to maintain healthy clock function. These breakthroughs will help preserve healthy behavioural rhythms, thereby contributing to improved physical and mental health throughout the population. In addition, we will establish and validate molecular markers that can predict and quantify disruptions in the biological clock and associated health problems, opening new research and therapeutic avenues. More information on individual projects can be found below.
Cluster leader: Laura Kervezee (LUMC)
Vice-cluster leader: Roelof Hut (RUG)
Senior advisor: Andries Kalsbeek (NIN)
The aim of this work package is to describe the mechanisms of light effects on behavior and cognitive performance in diurnal and nocturnal mammals and humans. The specific objectives are to:
- Quantify photoreceptor contribution on circadian entrainment and mental performance in humans.
- Unravel light effects on brain function, cognition and behavior in diurnal and nocturnal animals.
- Develop and test light sources that maintain circadian stability while enhancing specific performance.
The aim of this work package is to find effective timed exercise training and time-restricted eating schedules in order to prevent lifestyle-induced disturbances of metabolism and sleep-wake rhythms. Specific objectives are to:
- Determine the optimal timing of timed exercise and time-restricted eating to improve glucose metabolism and sleep-wake rhythms.
- Identify brain mechanisms that strengthen the long-lasting beneficial effects of timed exercise.
- Determine if outdoor daylight contributes to the beneficial health effects of exercise training.
The overall aim of this work package is to design biomarker-based personalized prevention strategies to promote sustainable health and performance of shift workers. Specific objectives are to:
- Identify and validate biomarkers to quantitatively assess shift work-related circadian disturbance.
- Determine whether these biomarkers can be used to predict later life health risk.
- Develop evidence-based measures to maintain fitness and employability of shift workers.
This work package aims to develop educational programs and interventions that target (knowledge of) the biological clock of adolescents and university students. Specifically, our objectives are to:
- Develop and evaluate an educational program for use in secondary education, which ensures a deep understanding on behalf of the learners regarding their daily behavior, the impact on the biological clock, and ultimately the consequences for health.
- Develop and evaluate interventions that target the biological clock and improve the sleep patterns of university students in order to prevent the development/exacerbation of mental health problems.
Cluster 2 – Clocks in Healthcare
In Cluster 2, we will improve clinical outcomes in patients throughout the healthcare system by building upon the principles that govern the biological clock. We will investigate the long-term effectiveness of providing rhythmic conditions in neonatal intensive care units, study the role of light and social rhythms to improve mental health, develop new compounds designed to strengthen and restore clock function, and determine the optimal timing of immunotherapy, for example in the context of vaccinations and cancer therapy. More information on individual projects can be found below.
Cluster leader: Niki Antypa (Leiden Univ)
Vice-cluster leader: Ines Chaves (Erasmus MC)
Senior advisor: Bert van der Horst (Erasmus MC)
The overall aim of this work package is to improve development and health by strengthening circadian rhythms early in life. Specifically, our objectives are to:
- Identify epigenetic health risk markers in preterm infants and establish a circadian rhythm assay as a predictor of later-life circadian performance.
- Identify a clinical intervention (e.g. maternal rhythm, feeding timing and composition, light conditions) that improves circadian development and postnatal growth and health.
- Elucidate the mechanisms underlying the effectiveness of intervention, by monitoring sleep, neurodevelopment and brain morphology.
The overall aim of this work package is to restore and optimize the biological clock of mental healthcare patients with depression. The specific objectives are to:
- Understand the brain mechanisms that make light therapy a successful antidepressant treatment.
- Optimize chronotherapeutic interventions to improve well-being and facilitate recovery in depressed patients.
- Identify markers that predict response to antidepressant treatments and enable treatment selection.
The ultimate goal of this work package is to determine which time of the day vaccines should be administered to offer the best protection by the vaccine. Specifically our objectives are to:
- Determine the effect of dosing time on the antibody response to vaccination and the resulting change in burden of disease.
- Establish the role of the circadian clock in the response to cancer immunotherapy.
There are three objectives in this work package. The aim is to:
- Identify, validate and optimize probe compounds that enhance clock amplitude – such compounds are to reset/repair a damaged clock, in cell cultures and murine neuronal networks
- Develop chemical probes from these compounds – such compounds will be designed and synthesized in house, harboring vectors for covalent interaction and tagging
- Identify clock protein targets that the chemical probes interact with – through a number of genomic, transcriptomics and proteomics approaches.
Cluster 3 – Clocks in the Environment
Innovative techniques and solutions will be used to reduce the disruptive effects of our 24-h society on the biological clocks of plants and animals. We will detail, and scale up from, the physiological and behavioral effects of light pollution in order to understand the effects on the fitness of organisms, and their cascading effects on complete ecological communities. By developing and implementing effective new strategies that protect the 24-h rhythm in urban, rural, and natural ecosystems, we will minimize the detrimental effects of light pollution on the environment. This will contribute to slowing the alarming decline in global biodiversity. More information on individual projects can be found below.
Cluster leader: Kamiel Spoelstra (NIOO-KNAW)
Vice-cluster leader: Martina Vijver (Leiden Univ)
Senior advisor: Joke Meijer (LUMC)
In this work package, we will study the mechanisms by which light pollution affects the behavior and physiology of both diurnal and nocturnal species, identifying strategies to preserve clock function. The specific objectives are to:
- Determine the effects of light pollution on the robustness of the 24-hour rhythm in nocturnal and diurnal species, thereby revealing potential strategies for minimizing the effects of light pollution.
- Determine the effects of nocturnal light on seasonal rhythms such as reproduction (mammals, using lab studies) and migration (fish, using field studies).
- Implement prevention strategies developed in objective 2 in order to protect biodiversity.
The main aim of this work package is to quantify the temporal mismatching effects of light pollution in foodwebs, ranging from plants and herbivores to predators. The specific objectives are to:
- Identify how different forms of light pollution lead to temporal (circadian) mismatches between plants, and the activity patterns of herbivores (insects) and predators (bats and birds).
- Quantify the role of light pollution on changes in pollination and pest development through temporal mismatches in foodweb interactions.
- Develop practical strategies to minimize the effect of light pollution on temporal mismatches in foodwebs, and to maximize provisioning of ecosystem services.
The overall aim of this work package is to determine the extent to which the 24-hour nature of cities results in the change of species’ rhythms. The specific objectives are to:
- Establish modification of biological clocks in urban environments.
- Develop strategies to reduce disturbance of biological clocks in cities.
- Actively involve urban residents to improve measurements of light pollution.
The overall aim of this work package is to expand knowledge on the most dramatic ecological impact mechanism of light pollution, namely phototaxis in insects and migratory birds. Species-group specific spectral responses will be measured in lab and field settings, leading to evidence based spectral light tuning that minimizes ecological impact. The specific objectives are to:
- Experimentally and empirically assess species specific impact of light color on phototaxis of insects and birds.
- Behavioral and neuro-physiological characterization of light spectrum specific insect phototaxis.
- Implement recommendations based on objectives 1 and 2 to reduce location-specific impact of light by spectral tuning.
The BioClock Consortium is funded by the NWA-ORC programme of the Dutch Research Council (NWO; project number 1292.19.077).