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IL-1 signalling and developmental programming of offspring metabolic health

48 months
Approved budget:
Dr Clare Reynolds
Health issue:
Obstetric complications/perinatal care
Proposal type:
Emerging Researcher First Grant
Lay summary
Unravelling how early life in the womb adversely affects future disease risk of the child is critical to reversing the obesity and diabetes epidemic. Over the last two decades, maternal obesity has been exposed as a major driving force in the predisposition to chronic adult onset conditions in offspring including cardiovascular disease and metabolic syndrome. These conditions are strongly associated with a state of persistent low-grade inflammation. IL1R1 is a key signalling mediator which bridges metabolic and inflammatory systems. We hypothesise that IL1R1 deficiency will dampen maternal metabolic stress, decreasing placental dysfunction resulting in improved offspring outcomes, which negates the detrimental metabolic and cardiovascular trajectory of adult offspring subjected to maternal diet-induced programming. By examining traditional developmental programming models within the context of immune deficiency, we can further the mechanistic understanding of the early life triggers which predispose individuals to non-communicable disease, potentially revolutionising the way we tackle adult disease.