Descrizione del progetto
Uno sguardo più da vicino alle origini dell’orologio circadiano
Il ritmo circadiano è un processo biologico che si verifica ogni 24 ore negli organismi viventi, innescato da segnali ambientali. Questo sistema di temporizzazione circadiana inizia durante la gravidanza e persiste per tutta la vita dell’individuo. Svolgendo il ruolo di orologio circadiano centrale, il nucleo soprachiasmatico (SCN) sincronizza la nostra biologia e il nostro comportamento. Il progetto StarTicking, finanziato dal CER, studierà quando e come si origina questo orologio. Attraverso un approccio multidisciplinare, si studierà il pacemaker centrale sia nei topi che negli esseri umani al fine di spiegare i meccanismi fisiologici sottostanti. Per convalidare questi risultati, i ricercatori svilupperanno un modello umanoide. Questa impresa riveste un’importanza significativa per comprendere l’impatto dei disturbi circadiani precoci sugli esiti comportamentali.
Obiettivo
The 24-h (circadian) timing system develops during the perinatal period and rules our physiology later in life. It has the essential task of anticipating daily recurring changes in the environment (day/night) to find the best time for each molecular and cellular process. It is organised hierarchically, with a master pacemaker in the hypothalamic suprachiasmatic nucleus (SCN), which is able to perceive environmental light and tell the body what time is it. Our modern 24/7 lifestyle favours a disruptive environment for the circadian system, which is especially negative during pregnancy. We have found, in mice and pre-term infants, that when mothers are exposed to glucocorticoids (GCs) at the wrong time of day, the offspring show behaviour disorders later in life. Our mechanistic findings showed for the first time, a role of the foetal clock before birth, challenging the view on the clock being immature and non-functional.
StarTicking proposes to answer a long-standing question in the field: When and how the circadian clock starts ticking. With a multidisciplinary and integrated approach, we will go beyond the state-of-the-art to understand mechanistically the development of the central circadian pacemaker in mice and humans. We will investigate:
1) How the SCN forms by a detailed assessment of the developmental trajectory of the mouse SCN with single cell resolution.
2) When the SCN becomes functional by testing a yet unexplored player: Astrocytes as drivers of the gain of functionality of the mouse SCN.
3) What the influence of the early environment on the human SCN maturation is. The generation of a human SCN organoid will allow us to test maternal signals in vitro with high-throughput. We will link mechanistic findings to the development of SCN-driven rhythms in a cohort of pre-term babies.
StarTicking will provide ground-breaking mechanistic evidence and valuable knowledge to alleviate the behavioural consequences of the circadian disruption early in life
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
48940 Leioa
Spagna