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

你的童年塑造了你未来的成年生活。从受孕到青春期和成年早期，关键的发展里程碑受到一系列因素的影响；有些是遗传的，而另一些则源于物理和/或社会环境因素。对于神经精神疾病，众所周知，早期生活是至关重要的，因为四分之三的精神健康问题在24岁之前出现。然而，主要的临床和科学挑战仍然存在：确定大脑发育在生命早期何时受到干扰，为什么它会表现为如此衰弱的行为结果，以及如何建立潜在病理机制的模型可以用于治疗。在MURIDAE集群中，我们将通过使用小鼠模型来充分表征这些关键的时间窗口来解决这些重要的挑战。一是建立产后早期综合研究新思路。其中的关键是将早期生活中行为变化的出现与大脑发育和连通性的变化以及与成人行为的变化联系起来。然后，我们将把这个新颖的整体平台应用于神经精神疾病的新遗传小鼠模型的研究。为了提高我们小鼠模型的有效性，我们将以临床合作伙伴的最新基因组发现为指导。我们的第一个目标将是在这些模型中确定成年异常的大脑和行为的早期变化。这将使我们能够在生命早期为神经精神疾病定义新的、关键的干预点。然后，我们将通过使用最新的基因技术和/或治疗方法挽救我们的工程突变来测试这些早期干预点的临床相关性。这项雄心勃勃的工作计划将使我们能够更好地理解神经精神疾病背后的共同机制，并在生命早期定义新的、关键的干预点，从而改善临床结果。

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.