MRC Transition Support CDA Jamie Walker

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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.