ECR Spotlight is a series of interviews with early-career authors from a selection of papers published in Journal of Experimental Biology and aims to promote not only the diversity of early-career researchers (ECRs) working in experimental biology during our centenary year but also the huge variety of animals and physiological systems that are essential for the ‘comparative’ approach. William Joyce is an author on “ Evolution and divergence of teleost adrenergic receptors: why sometimes ‘the drugs don't work’ in fish”, published in JEB. William conducted the research described in this article while a postdoc at Aarhus University, Denmark. He is now a postdoc in the lab of Borja Ibáñez at National Centre for Cardiovascular Research, Madrid, Spain, investigating the regulation of the cardiovascular system in vertebrates, from the integrative control of cardiac output to the molecular evolution of cardiac proteins.

William Joyce

Describe your scientific journey and your current research focus

I was introduced to the field of comparative physiology by Professor Holly Shiels during my undergraduate (BSc) degree in Zoology at the University of Manchester (UK). Holly's dynamic and engaging lectures on animal physiology included descriptions of the weird and wonderful hearts of reptiles, which captivated me and I soon found myself working on reptile heart physiology (especially cardiovascular regulation) with Professor Tobias Wang in the Zoophysiology Section at Aarhus University (Denmark). After my PhD, I was privileged to receive a postdoctoral fellowship from the Novo Nordisk Foundation (Denmark), which enabled me to first work with Professor Steve Perry (University of Ottawa, Canada) and then return full circle to Holly Shiels' group in Manchester, whilst remaining affiliated with Aarhus University. During this period, I became more interested in molecular and cellular physiology, as well as evolutionary (phylogenetic) analyses, which together underscore our recent Review article. I have recently joined the biomedically orientated group of Borja Ibáñez at the National Centre for Cardiovascular Research in Madrid (Spain), where I intend to apply the principles of comparative physiology to contribute to translational investigations using different model species.

How would you explain the main message of your Review to a member of the public, and the broader impact of research in this area?

The article deals with adrenergic receptors, which are responsible for detecting adrenaline that may be released into the circulation during stress or exercise, and transducing the signal to produce physiological responses in a tissue. There is a rich back catalogue of literature on adrenergic control in fish, and the field is burgeoning now that zebrafish are widely used as model organisms, for example as a pharmacological screening tool. Such studies typically involve employing drugs that either activate or inactivate different adrenergic receptors. The effects of such drugs, purportedly acting on specific receptors, have been defined by mammalian pharmacology. However, often overlooked is that fish have a different repertoire of receptors, owing to their distinct evolutionary history. The main message of the Review is that it is essential to appreciate that typical adrenergic drugs may not have the same effects in fish as when applied in mammals. Of course, fish are still valuable study organisms to understand adrenergic regulation, but the results of such studies should be interpreted carefully.

What was your approach in organising background material and shaping this Review?

For this, and my previous Review papers, I very much like to take a slow and steady approach (as far as professional deadlines allow; of course, sometimes thesis hand-ins or grant reporting might not allow this). I began to develop the idea for this Review about 4 years ago when I first started working with Steve Perry at the University of Ottawa and was studying adrenergic regulation of the heart in larval zebrafish using various pharmacological agents. I soon realised that sometimes the drugs were reported to have quite different effects on fish compared with mammals. Steve told me about similar previous tales in the fish liver and red blood cells (which also became prominently featured in this Review). At that point, I started to organise a document with notes and gradually began to find a structure for the Review. Later, when working with Holly Shiels at the University of Manchester, she explained – over a burger and beer one evening – having had the same tribulations studying adrenergic regulation of fish cardiomyocytes. She introduced me to Jim Warwicker, also at the University of Manchester, an expert in structural bioinformatics and molecular modelling, as he and Holly had already begun to find some structural peculiarities in fish receptors. This perspective fitted in perfectly with the material I was gathering on why sometimes ‘the drugs don't work’ in fish. Once all the patiently collected pieces were in place, putting together the final manuscript was quite quick.

Histological staining of the loggerhead turtle heart, including the undivided ventricle (bottom) supplied by two atria (top). Adapted from Costello et al. (2022) (doi:10.1242/jeb.244864). Experiments and imaging performed by Leah Costello while working under the co-supervision of William Joyce.

Histological staining of the loggerhead turtle heart, including the undivided ventricle (bottom) supplied by two atria (top). Adapted from Costello et al. (2022) (doi:10.1242/jeb.244864). Experiments and imaging performed by Leah Costello while working under the co-supervision of William Joyce.

What do you see as the main value of Review/Commentary-type articles?

I generally believe research articles should be concise (I was once advised to keep a typical ‘Introduction’ section to three paragraphs), focused and hypothesis driven. In contrast, Reviews allow much more creativity and space to explore ideas. When writing a Review, I often think about a target audience of graduate students – or indeed any newcomer to a field – and hope to provide an informative and engaging resource. I also think it is essential to cover both historical as well as modern literature. In our recent Review, for example, ‘Box 1’ gives a dedicated historic overview of how and when different adrenergic receptor sub-types were discovered.

Are there any important historical papers from your field that have been published in JEB?

With respect to my enduring fascination with reptile hearts, the 1974 publication ‘Ventricular outflow dynamics in the lizard, Varanus niloticus’ by Millard and Johansen (doi:10.1242/jeb.60.3.871) revealed a remarkable capacity for the single ventricle of varanid (monitor) lizards to effectively separate low pulmonary pressures and high systemic blood pressures. In most reptiles, the ventricle acts as a single pressure pump, perfusing the pulmonary and systemic circulations with equivalent systolic pressures. In mammals and birds (endotherms), pressure separation is more obviously achieved by a complete ventricular division, giving rise to the right and left ventricles. The varanid lizard heart is anatomically undivided but becomes functionally divided during contraction, owing to a prominent ‘muscular ridge’. A similar phenomenon has since also been reported in python hearts by Wang and colleagues (also in JEB), in 2003 (‘Ventricular haemodynamics in Python molurus: separation of pulmonary and systemic pressures’; doi:10.1242/jeb.00681). The ability to maintain low pulmonary pressures allows a thin blood–gas barrier to promote gas exchange whilst the high systemic blood pressure can aid organ perfusion, especially during exercise. Varanid lizard and python hearts thus emerge as something of an intermediate between typical reptiles and endotherms, but the precise evolutionary pressures that gave rise to these adaptations still remain something of a mystery.

Are there any modern-day JEB papers that you think will be the classic papers of 2123?

It goes without saying that in 100 years the world will be very different, particularly given the ongoing climate emergency. JEB is the premier avenue for papers on environmental animal physiology, including the effects of anthropogenic stressors. For example, Lefevre and colleagues recent (2021) authoritative review, ‘The role of mechanistic physiology in investigating impacts of global warming on fishes’ (doi:10.1242/jeb.238840) provided an important synopsis that I think will stand the test of time and continue to shape important future work in the area.

What changes do you think could improve the lives of early-career researchers, and what would make you want to continue in a research career?

The intense, cut-throat competition of securing grant funding is draining. I am a big fan of the concept of ‘universal basic research funding’, i.e. a guaranteed modest funding source for established researchers. This sort of money can go a long way to support research students to embark on creative, exploratory projects. I believe it would provide a lifeline for early-career comparative physiologists in particular, because it can otherwise sometimes be difficult to ‘sell’ big ideas to large funding bodies as the immediate translational potential of a project might not be obvious.

In terms of making ambitious projects more achievable, the availability of other small funding sources can also be a huge help to grow ideas. A good example is The Company of Biologists' ‘Research Partnership Kickstart Travel Grants’ to foster new collaborations.

I am also intrigued by the idea of introducing a partially randomised system to the awarding of grant funding. After expert review, all grants that meet a very high standard (i.e. a pre-determined threshold on a given scoring system) can be separated by a ‘lottery’, instead of splitting hairs and searching for unwarranted reasons for rejection. I think this can contribute to a more honest and more transparent system.

William Joyce’s contact details: National Centre for Cardiovascular Research, 28029 Madrid, Spain.

E-mail: wimjoyce92@gmail.com

Joyce
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W.
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Warwicker
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J.
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Shiels
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H. A.
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Perry
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S. F.
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2023
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Evolution and divergence of teleost adrenergic receptors: why sometimes ‘the drugs don't work’ in fish
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J. Exp. Biol.
226
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jeb245859
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