Molecular Physiology: signalling by small ions
We study how small ions trigger and modulate the function of cells in human tissue. By understanding their effects on the body’s physiology, we’re able to understand the fundamental role they play in health and disease.
In particular, our research focuses on the roles of pH and calcium on the physiology of the heart and cancer. These two tissues are similar in that they both have high metabolic rates, complex signalling pathways and major implications on human health. Both also experience high acid loads, thanks to their high metabolic rate, and are strongly influenced by the presence of calcium, as its role in signalling controls heartbeat and tumour progression.
We use molecular imaging to study the role of hydrogen and calcium ions in these tissues. Crucially, though, we take a bottom-to-top approach: from using confocal fluorescence microscopy to understand sub-cellular behaviour, all the way up to employing magnetic resonance to learn about the the whole-organ response. Based on our experimental work, we are able to build mathematical models that can be used to predict how cellular behaviour varies depending on the presence of small ions. Our approach is, necessarily, recursive: our observations feed our models, which are then validated against further experiments.
In our approach to validation, however, we differ from many similar groups around the world. We are pioneering the use of 3D clusters of cells, known as spheroids, in the lab, which allows us to mimic tissue much more accurately. While it makes our work more time-consuming and complex, it provides much more useful results than single, isolated cell preparations ever can. Currently we’re using these approaches to understand the importance of mitochondria in cardiac cell physiology and the links between pH and cancer development.
Ultimately, our research programme, built upon understanding the role of small ions in cardiac and tumour tissue, helps provides a more complete understanding of physiology, highlights different physiological needs and challenges, and fuels technological progress.