MRC Transition Support CDA Jamie Walker

振荡活动在我们的生理中根深蒂固，当这些振荡被扰乱时，这可能会对我们的健康产生重大后果。下丘脑-垂体-肾上腺(HPA)轴就是一个很好的例子，它是人体内控制皮质醇等“应激激素”释放的重要系统。这些荷尔蒙的波动调节许多重要生物功能的活动，并确保身体处于对压力做出反应的理想状态。但是，生命早期的压力经历，或过大或过长的压力，可能会导致HPA轴活动的长期中断，这反过来会对大脑功能和我们的身心健康产生影响。我的奖学金的首要目标是了解HPA轴如何控制激素分泌的这些振荡；这些信息对于了解这些激素模式如何以及为什么在疾病中变化至关重要。在职业发展奖(CDA)的支持下，我正在使用定量技术和最先进的实验方法来了解皮质醇节律是如何产生的。到目前为止，我已经研究了脑下垂体细胞如何协调HPA轴的活动，并展示了来自脑下垂体本身的动态荷尔蒙信号是如何被肾上腺解码以控制皮质醇分泌的。虽然在单个腺体水平上研究激素调节提供了有价值的见解，但它很少告诉我们HPA轴的各个组成部分如何相互作用以产生激素分泌的振荡模式。归根结底，影响我们生理的是这种“系统级”的振荡活动，也正是这种系统级的活动在疾病中中断。由于不可预见的因素对我的研究势头产生了重大影响，到目前为止，我无法产生这些系统级的输出，这是我的CDA的最高目标，也是在我的领域获得额外资金的关键。然而，基于我在我的项目的脑下垂体和肾上腺方面取得的重大进展，我相信，有了为期两年的过渡支持奖，我将成功地交付这些系统级的产出，这将形成我开发有竞争力的进一步资金申请所需的平台。

Oscillating activity is ingrained in our physiology, and when these oscillations become disrupted, this can have major consequences for our health. A good example of this is the hypothalamic-pituitary-adrenal (HPA) axis, a vital system in the body controlling the release of 'stress hormones' such as cortisol. Oscillations in these hormones regulate the activity of many important biological functions, and ensure the body is in an ideal state to respond to stress. But stressful experiences early in life, or excessively-large or prolonged periods of stress, can lead to long-lasting disruptions in HPA axis activity, which in turn has consequences for brain function and our physical and mental well-being. The overarching aim of my fellowship is to understand how the HPA axis controls these oscillations in hormone secretion; this information will be critical for understanding how and why these hormone patterns change in disease.Supported by a Career Development Award (CDA), I am employing quantitative techniques and state-of-the-art experimental approaches to understand how cortisol rhythms are generated. To date, I have investigated how cells in the pituitary gland coordinate the activity of the HPA axis, and have shown how dynamic hormonal signals from the pituitary gland itself are decoded by the adrenal glands to control cortisol secretion. Whilst studying hormone regulation at the level of individual glands provides valuable insight, it tells us little about how the various components of the HPA axis interact with one another to generate oscillating patterns of hormone secretion. Ultimately, it is this 'system-level' oscillating activity that effects our physiology, and it is this system-level activity that becomes disrupted in disease.Due to unforeseeable factors that have had a significant impact on my research momentum, I have so far been unable to produce these system-level outputs that are the uppermost aim of my CDA, and are critical to secure additional funding in my field. However, based on my significant progress in the pituitary and adrenal aspects of my project, I am confident that with a 2-year Transition Support Award, I will successfully delivery these system-level outputs, which would form the platform I need to develop competitive further funding applications.