Objective 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 Fields of science medical and health sciencesclinical medicineobstetricsmedical and health sciencesbasic medicinephysiology Keywords circadian clock suprachiasmatic nuclei (SCN) mouse human development pregnancy early environment premature babies glucocorticoids neurons astrocytes organoids foetal brain single nuclei RNA seq organotypic Per2Venus in utero electroporation ex vivo electroporation lineage tracing Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2022-COG - ERC CONSOLIDATOR GRANTS Call for proposal ERC-2022-COG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Coordinator ACHUCARRO BASQUE CENTER FOR NEUROSCIENCE FUNDAZIOA Net EU contribution € 1 955 875,00 Address Parque cientifico de la universidad del pais vasco rriko unibertsitatea edificio sede plant a 3 48940 Leioa Spain See on map Region Noreste País Vasco Bizkaia Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
