MRC Transition Support CDA Jamie Walker

MRC 过渡支持 CDA Jamie Walker

• 批准号: MR/T032480/1
• 负责人: Jamie Walker
• 金额: $ 27.52万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT032480%2F1
• 关键词: MRC; Transition; Support; CDA; Jamie

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.

振荡活动在我们的生理学中根深蒂固，当这些振荡被破坏时，可能会对我们的健康产生重大影响。下丘脑-垂体-肾上腺（HPA）轴就是一个很好的例子，它是体内控制皮质醇等“压力激素”释放的重要系统。这些激素的波动调节许多重要生物功能的活动，并确保身体处于应对压力的理想状态。但生命早期的压力经历，或者过大或长时间的压力，可能会导致 HPA 轴活动的长期破坏，进而对大脑功能和我们的身心健康产生影响。我的研究项目的首要目标是了解 HPA 轴如何控制激素分泌的这些波动；这些信息对于理解这些激素模式在疾病中如何以及为何发生变化至关重要。在职业发展奖 (CDA) 的支持下，我正在采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。迄今为止，我已经研究了垂体细胞如何协调 HPA 轴的活动，并展示了肾上腺如何解码来自垂体本身的动态激素信号以控制皮质醇的分泌。虽然研究单个腺体水平的激素调节提供了有价值的见解，但它几乎没有告诉我们 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。最终，正是这种“系统级”的振荡活动影响了我们的生理机能，也正是这种系统级的活动在疾病中被打乱。由于不可预见的因素对我的研究动力产生了重大影响，我到目前为止无法产生这些系统级输出，而这些系统级输出是我的 CDA 的最高目标，并且对于在我的领域获得额外资金至关重要。然而，基于我在项目的垂体和肾上腺方面取得的重大进展，我相信，凭借为期 2 年的过渡支持奖，我将成功交付这些系统级输出，这将形成我开发有竞争力的平台所需的平台进一步的资助申请。