Project description
A closer look at circadian clock origins
The circadian rhythm is a biological process that occurs every 24 hours in living organisms, triggered by environmental cues. This circadian timing system initiates during pregnancy and persists throughout an individual’s life. Playing the role of a central circadian clock, the suprachiasmatic nucleus (SCN) synchronises our biology and behaviour. The ERC-funded StarTicking project will study when and how this clock originates. Through a multidisciplinary approach, it will investigate the central pacemaker in both mice and humans to explain the underlying physiological mechanisms. To validate these findings, researchers will develop a humanoid model. This undertaking holds significant importance in comprehending the impact of early circadian disruption on behavioural outcomes.
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
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
48940 Leioa
Spain