MURIDAE – Modalities for Understanding, Recording and Integrating Data Across Early life

Your childhood shapes your future adult life. From conception through adolescence and to early adulthood, key developmental milestones are influenced by a wide range of factors; some are inherited, while others stem from physical and/or social environmental factors. For neuropsychiatric disorders, it is well established that early life is critical as three-quarters of mental health problems emerge before the age of 24. Yet major clinical and scientific challenges remain: to determine exactly when brain development is perturbed early in life, why it can manifest into such debilitating behavioural outcomes, and how modelling the underlying pathological mechanisms can be harnessed therapeutically. In the MURIDAE Cluster, we will address these important challenges by using mouse models to fully characterise these critical time-windows. First, we will establish new, integrated approaches for studying the early postnatal period. The key to this will be linking the emergence of changes in behaviour in this early life period with changes in brain development and connectivity, and also with adult behaviour. We will then apply this novel, holistic platform to the study of new genetic mouse models of neuropsychiatric disorders. To improve the validity of our mouse models, we will be guided by the latest genomic discoveries made by our clinical partners. Our first aim will be to identify early changes in brain and behaviour that are antecedents of adult abnormalities in these models. This will allow us to define novel, critical intervention points for neuropsychiatric disorders during early life. We will then test the clinical relevance of these early intervention points by rescuing our engineered mutations using the latest genetic techniques and/or therapeutics. This ambitious plan of work will allows us to better understand the shared mechanisms that underlie neuropsychiatric disorders and define novel, critical intervention points during early life that will improve clinical outcomes.