Research Lines

Evolution of cardiac proteins

The action of adrenaline on the heart - including increasing heart rate and contractility - is key to allow flexibility to change cardiac function in response to environmental stressors or activity. 

My main current focus is on understanding the evolution of adrenergic signalling in the heart, from the receptors involved in initiating intracellular signalling to the regulation of proteins in the sarcomere. I am particularly interested in the protein ‘cardiac troponin I’, which, as part of the troponin complex, influences the Ca2+ sensitivity of the myofilaments that generate force during cardiac contraction. This involves combining my expertise in animal physiology with the insights from collaborators in comparative genomics and transcriptomics. 

Environmental physiology

I am interested in how environmental factors, especially low oxygen (hypoxia) and temperature, affect physiology of ectothermic ('cold-blooded') vertebrates.

Low oxygen (hypoxia) is common in aquatic environments, and owing to climate change (pollution, wildfires, ocean warming) is becoming ever more frequent and severe. Severe hypoxia can be responsible for mass fish mortality, whilst even mild hypoxia can lead to more subtle changes with an ecosystem. The hypoxia tolerance of individual fish is at least partially determined by how well their heart can continue to function when environmental oxygen levels fall. As such, I have become particularly interested in understanding the determinants of cardiac hypoxia tolerance in fish, from the molecular regulation mediated via hypoxia inducible factors (HIFs) to the control of heart rate in the intact animal during environmental hypoxia.

I have also been heavily involved in a research line studying the cardiovascular systems of Antarctic icefish, which are enigmatic species and represent the only adult vertebrates that lack red-blood cells and hence have translucent white blood. This is possible because they inhabit such cold water (~0°C) with high dissolved oxygen levels, as well as allowing a low metabolic rate. However, the Antarctic peninsula is rapidly warming, so these specialist fish may be especially imperilled. The first cardiovascular measurements were conducted on icefish in the 1970s, but lacked the precision of modern technologies. In a 2017 expedition, I was part of a large international collaboration to study icefish physiology, and I specifically conducted the experiments to measure cardiac output and other cardiovascular parameters. The experiments surprisingly showed that the icefish cardiovascular system could operate well as high as 8°C under acute warming, a temperature beyond future climate predictions in the region, so are more likely vulnerable to ecosystem collapse than intrinsic physiological failure.

Regulation and limits of cardiac output

Cardiac output, the amount of blood pumped by the heart per minute, is determined by heart rate (the number of beats per minute) and stroke volume (the amount of blood pumped per beat). When we exercise, one of the most obvious responses is that heart rate increases. Yet this does not mean that heart rate is driving the change in cardiac output. One of my most controversial research pursuits has been to argue that, whilst heart rate appears to be an obvious parameter to change, it is within the relevant range not directly changing cardiac output, which is instead determined by the peripheral circulation (vasculature). This is counterintuitive and is still not widely appreciated, but has major implications on understanding oxygen transport, including in humans. We have built on early studies in mammals to show that these principles transcend across vertebrate species, being a feature of the cardiovascular systems of fishes and reptiles.