Peter J Hunter & Nicolas P Smith, University of Auckland, New Zealand

David J Paterson, University of Oxford, UK

https://doi.org/10.36866/pn.112.18

The computational physiology link between Oxford and Auckland had its roots in 1972 when Peter Hunter began a Doctorate with a Commonwealth Scholarship at Oxford. The Oxford engineer Don Schultz (also a New Zealander) had begun a collaboration with the physiologist Derek Bergel a few years earlier to bring engineering approaches and technologies to the study of the circulation. Peter joined this team, under the supervision of Derek Bergel in the University Laboratory of Physiology – now the Department of Physiology, Anatomy and Genetics. Derek’s lab was along the corridor from Denis Noble and Julian Jack, and although Peter’s thesis topic was on ventricular mechanics, he became involved in Denis’ modelling of cardiac cell electrophysiology, a collaboration that, 20 years later, led to the establishment of the Cardiac Physiome project.

Following a postdoc from 1975 to 1979 at the Rutherford Laboratory and St Catherine’s College, Peter returned to a lectureship in the Department of Theoretical and Applied Mechanics (now Engineering Science) at Auckland University in 1980 and a new collaboration with Bruce Smaill in the Department of Physiology at Auckland on measuring and modelling the structure and mechanical function of the heart began. An invitation to Denis Noble to give a lecture in Auckland in 1985 established the Auckland–Oxford collaboration on bringing Denis’ cardiac cell models into the context of the Auckland whole heart models and began the Cardiac Physiome project. At the invitation of the International Union of Physiological Sciences at the St Petersburgh Congress in 1997, this was expanded to become the IUPS Physiome Project under the leadership of Denis, Peter and, from the University of Washington, Jim Bassingthwaighte.

The next stage of the Oxford–Auckland link began in 1995 when David Paterson (who succeeded Derek Bergel at Merton College) bought a 256 electrode mapping system from the Auckland group and requested a postdoc to help use it for studies of cardiac activation. Marty Nash, who had been a PhD student in Auckland, came to join David’s lab in Oxford (1996–2002), followed shortly afterwards by Chris Bradley (1999–2009). The late Andrew Pullan from Auckland then spent two sabbatical summers at Oxford as the team worked on experimental validation of the ‘inverse problem’ of electocardiography in the pig (1999–2001). At the same time (1999), another New Zealander, Nic Smith, came to take up a postdoc under Denis working on coronary flow. Nic returned to a lectureship in Auckland in 2001 and then returned back to the Computer Science Lab in Oxford a few years later in 2006, bringing another group of young kiwis with him. Following a period at KCL where Nic led the establishment of a new biomedical engineering programme at St Thomas’ Hospital, he returned to Auckland, where he is now Dean of Engineering. Marty and Chris also returned to Auckland having benefitted from a fruitful collaboration in London with Peter Taggart where the Oxford mapping system found its way to human mapping during cardiac surgery.

A key milestone for the Cardiac Physiome Project was the award of a programme grant by the Wellcome Trust to David Paterson and Peter Hunter in 2005–2010. This provided the funding to establish the infrastructure for the modelling standards, software tools and model repository now underlying the Physiome Project. Peter Hunter was appointed a visiting Professor in Computational Physiology at Oxford. When David Paterson became Editor-in-Chief of Experimental Physiology, then The Journal of Physiology, he recruited Peter and Nic Smith to lead the editorial area of computational physiology, where several special issues were published highlighting the importance of modelling in the reassembly of physiological data to inform the next stage of experimental design.

Today, this long collaboration still continues with David Paterson having an Honorary Professorship at the Auckland Bioengineering Institute where he is a co-investigator on two long-running HRC programme grants led by Peter and Bruce Smaill. Ten years after Nash, Bradley, Pullan and Paterson published their experimental-modelling framework for the ‘inverse problem’, Bruce and David have revisited this area and refined the framework. Indeed, the collaboration between the Oxford and Auckland groups has been further connected by a new funding opportunity from NIH SPARC (Stimulating Peripheral Activity to Relieve Conditions), where the autonomic nervous system is being connected to end-organ function and modelled to understand how the nervous system controls physiological function in diseased states, as a prelude for target discovery and device therapy.

Further Reading

Hunter PJ, McNaughton PA, Noble D (1975). Analytical models of propagation in excitable cells. Progress in Biophysics and Molecular Biology 30, 99–114.

Kohl P, Noble D, Winslow RL, Hunter PJ (2000). Computational modelling of biological systems: tools and visions. Philosophical Transactions of the Royal Society 358, 579–610.

Hunter PJ, Borg TK (2003). Integration from proteins to organs: The Physiome Project. Nature Reviews Molecular and Cell Biology 4(3), 237–243.

Nash MP, Bradley, CP, Cheng LK, Pullan AJ, Paterson DJ (2000). An in-vivo experimental-computational framework for validating ECG inverse methods. Intl. J. Bioelectromagnetism 2(2).

Pullan AJ, Paterson DJ, Greensite F (2001). Non-invasive imaging of cardiac electrophysiology. Phil. Trans. R. Soc. Lond. A 359(1783), 1277–1286.

Tao T, Paterson DJ, Smith NP (2011). A model of cellular cardiac-neural coupling capturing the sympathetic control of sinoatrial node excitability in normotensive and hypertensive rats. Biophysical J. 101(3), 594–602.

Nash MP, Bradley CP, Paterson DJ (2003). Imaging electrocardiographic dispersion of depolarization and repolarization during ischemia: simultaneous body surface and epicardial mapping. Circulation 107, 2257-2263.

Crampin EJ, Halstead M, Hunter PJ, Nielsen PMF, Noble D, Smith NP, Tawhai M (2004). Computational physiology and the physiome project. Exp. Physiol. 89(1), 1-26.

Bear LR, LeGrice IJ, Sands GB, Lever NA, Loiselle DS, Paterson DJ, Cheng LK, Smaill BH (2018). How Accurate Is Inverse Electrocardiographic Mapping? A Systematic In Vivo Evaluation. Circ Arrhythm Electrophysiol 11(5), e006108.