Identifying circadian clock and mineralocorticoid receptor (MR) interactions in heart disease

Summary The mineralocorticoid receptor (MR) is best known for the physiological control of blood pressure acting in the kidney under the control of the hormone aldosterone. The MR is also found in many other cell types including the heart and inflammatory cells where another hormone cortisol, not aldosterone, activates the receptor. Until recently the role of cortisol-MR signalling was largely unknown.

Project Details

Our recent studies identified reciprocal regulation of the molecular clock and the MR is and showed this interaction is important in heart disease. However, we do not understand the molecular mechanisms of the MR and molecular clock interaction and how these change across the circadian day. The outcomes of these studies will help us to understand how modern environmental circadian disruptors (e.g. jetlag) interfere with the body’s normal response to steroid hormones. Understanding how the molecular circadian clock and the MR interact will support development of chronotherapeutic approaches for cardiovascular disease therapies.
Techniques for this project will include cell culture, western blotting, FACS, immunocytochemistry, RT-PCR and molecular screening techniques.
This project will also involve bioinformatic analysis of large databases and potentially preclinical animal models.