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The circadian clock in day-active species: preserving our health in modern society

Description du projet

Les effets de l’éclairage nocturne sur les horloges circadiennes

Les rythmes circadiens dictent la structure de nos jours et de nos nuits. Il s’agit de l’horloge biologique interne qui régule notre cycle de sommeil et d’éveil sur une période de 24 heures. L’invention de l’ampoule électrique et l’exposition à la lumière pendant la nuit ont un côté obscur. Elles peuvent perturber notre horloge biologique. Le projet DiurnalHealth, financé par l’UE, étudiera les mécanismes qui dirigent le noyau suprachiasmatique (NSC) — le chronomètre central des mammifères — chez l’homme et chez d’autres espèces diurnes (actives le jour). Le projet testera l’hypothèse selon laquelle les mécanismes sont différents chez les espèces diurnes et les espèces nocturnes. Il identifiera les similarités et les différences en ce qui concerne leur réponse à la lumière, la synchronisation neuronale, ainsi que les résultats et la réponse à l’activité physique.

Objectif

Due to a significant increase in the use of artificial light in our 24h economy, the biological clocks of all living organisms, including humans, are severely disrupted. Many severe health disorders are consequences of clock disruption such as diabetes, sleep/mood disorders, cardiovascular disease, and immune dysfunction. The central timekeeper in mammals is the suprachiasmatic nucleus (SCN), and the mechanisms by which light disrupts integrity of the SCN has been well investigated in nocturnal species. In contrast, mechanisms of clock disruption in humans and other diurnal (day-active) species remain poorly defined. I have evidence that the mechanisms that drive SCN function are fundamentally different between nocturnal species and diurnal species. This defines my aim to restore proper clock function in diurnal species, including humans. To test this, in Objective 1 we will identify similarities and differences between nocturnal and diurnal clocks with respect to their i) response to light, ii) neuronal synchronization, iii) output, and iv) response to physical activity. Based on these findings, in Objective 2 we will develop novel strategies to manipulate and restore clock function in diurnal species. These objectives will be achieved using novel, state-of-the-art chronobiology methods including in vivo electrophysiology and Ca2+ and bioluminescence reporters—all in freely behaving day-active animals, as well as in slice preparations containing the SCN. For studies on the human SCN we record with 7-Tesla fMRI. This proposal will help establish a new basis for chronobiology with respect to the most suitable models for studying translational applications. The results will yield immediate benefits in terms of manipulating biological clock function among vulnerable populations in modern society, particularly the elderly, patients in intensive care, and shift workers.

Régime de financement

ERC-ADG - Advanced Grant

Institution d’accueil

ACADEMISCH ZIEKENHUIS LEIDEN
Contribution nette de l'UE
€ 2 166 755,63
Adresse
ALBINUSDREEF 2
2333 ZA Leiden
Pays-Bas

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Région
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 2 166 755,63

Bénéficiaires (2)