Leeds Computational Physiology Lab


Here at the Leeds Computational Physiology Lab, we aim to integrate experimental and numerical research approaches in order to better understand physiological mechanisms and processes in health and disease. We primarily focus on cardiac arrhythmias and exercise intolerance, and are interested in all aspects of healthcare research – from fundamental processes to improved therapies.

If you are interested in working with us, or visiting our lab to see what we get up to, please feel free to contact Mike (m.a.colman@leeds.ac.uk) or Al (a.p.benson@leeds.ac.uk).


Current group members

  • Mike Colman, University Academic Fellow

       

    Qualificatons:

    • MPhys (Hons)   - Physics with Theoretical Physics, University of Manchester, 2008
    • PhD                   - Physics (Computational Biology), University of Manchester, 2012

    Employment history

    • 2012-2014 : EPSRC Doctoral Prize Research Fellow, University of Manchester
    • 2014-2015 : UMIP Post-doctoral Research Associate, University of Manchester
    • 2015-2018 : MRC Strategic Skills Research Fellow University of Manchester/Leeds
    • 2016-present: University Academic Fellow, University of Leeds

    Research Interests

    • Multi-scale mechanisms of cardiac arrhythmias
    • Excitation-contraction coupling
    • Non-invasive diagnostic approaches
    Links: University page , Google scholar page

  • Al Benson, Lecturer of cardiovascular sciences

       

    Qualificatons:

    • Bsc (Hons)   - Sports Science, University of Leeds, 2003
    • PhD              - Computational Biology, University of Leeds, 2006

    Employment history

    • 2006-2008 : Post-doctoral Research Fellow, University of Leeds
    • 2008-2011 : MRC Special Training Fellowship, University of Leeds
    • 2011-2013 : Research Fellow, University of Leeds
    • 2013-present: Lecturer in Cardiovascular Sciences, University of Leeds

    Research interests

    My research interests are in the use of computational models, combined with magnetic resonance and other experimental techniques, to study cardiovascular physiology in health and disease. A particular focus has been the study of cardiac arrhythmias and exercise intolerance in heart failure.

    Cardiac arrhythmias

    Cardiac arrhythmias are a major cause of mortality and morbidity. Ventricular fibrillation is an often fatal arrhythmia in which the heart’s normal rhythm is disturbed when multiple electrical wavefronts continually re-excite the same tissue (re-entry); synchronous contraction of the ventricles is lost, circulation of the blood ceases and death occurs. Individuals with heart failure have a significantly increased risk of developing such arrhythmias.

    Computational cardiac models provide tools for examining the mechanisms underlying the onset of such arrhythmias, and interventions aimed at either preventing this onset or restoring normal sinus rhythm, as the data they provide can be dissected in time and space, and by parameters. Working closely with Dr Michael Colman, we develop biophysically-detailed computational models of the heart (at the sub-cellular, cellular, tissue and organ levels), and use these models to examine the roles that the structural (anatomical) and functional (electrophysiological and mechanical) changes seen in heart failure have on the initiation, maintenance and termination of cardiac arrhythmias such as ventricular fibrillation. To facilitate this, we have recently developed, in collaboration with Professor Ed White and others, an experimental “pipeline” where physiological measurements, optical mapping, novel diffusion tensor magnetic resonance imaging (DT-MRI) measurements and computational simulations can all be linked to study mechanisms leading to the initiation of cardiac arrhythmias.

    Exercise intolerance

    The ability to sustain muscular exercise is a key determinant of health, quality of life, and mortality. Poor exercise tolerance contributes to a downward spiral of inactivity, which is an “actual cause” of chronic disease, and the cardinal symptom of heart failure is a significant exercise intolerance which limits heart failure patients to a relatively sedentary lifestyle. However, the mechanisms limiting exercise tolerance remain poorly understood. Individuals capable of high rates of oxidative phosphorylation are able to tolerate sustained exercise at high levels. Achieving these high rates depends upon the effective integration of the physiological systems involved in O2 delivery and utilisation, clearance of CO2, and buffering of acid-producing reactions. However, because most conditions of physical activity are nonsteady-state, it is the integrated dynamics of these physiological systems that are most strongly related to exercise tolerance and longevity. Computational models allow us to study the intricately integrated (and therefore non-intuitive) relationships that exist between the different components of such a complex physiological system.

    Working closely with Dr Harry Rossiter, Dr Carrie Ferguson and Dr Bryan Taylor, we examine how the pulmonary, circulatory and muscular systems integrate during dynamic activity across the continuum of biological function, from elite athletes to heart failure patients. Experimental data – obtained using cardiopulmonary exercise testing (CPX), near-infrared spectroscopy (NIRS), magnetic resonance spectroscopy (MRS) and other techniques – are used to develop novel computational models integrating physiological systems dynamics. The data generated by these experiments and computational models help us understand how systems dynamics conflate to produce the rapid O2 uptake (VO2) kinetics that are a major determinant of exercise tolerance, and thereby contribute to improving exercise performance, health, quality of life, and longevity.

    Links: University page

  • Harley Stevenson-Cocks, Ph.D Student

       

    PhD Project

    The aims of my PhD project are to develop a biophysically-detailed computational framework for studying (patho)physiological propagation in rat cardiac tissue, that includes an accurate description of calcium handling, and to use this and existing models to identify and quantify mechanisms linking pathological remodelling of intracellular calcium handling and arrhythmogenesis at the subcellular, cellular and tissue levels.

    Supervisors/collaborators: Al Benson, Ed White, Mike Colman

    Qualificatons:

    • Bsc (Hons)   - Biomedical Sciences, University of Leeds, 2015
    Links: University page

    Related publications

    In press:

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Inward rectifier current downregulation promotes spontaneous calcium release in a novel model of rat ventricular electrophysiology." Computing in Cardiology 45, DOI:20.22489/CinC.2018.156.

    Conference Proceedings:

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Spontaneous calcium release is promoted by inward rectifier current downregulation in a novel model of rat ventricular electrophysiology." 11th Multidisciplinary Cardiovascular Research Centre Retreat, Glenridding, UK, 21-22 March 2019.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Inward rectifier current downregulation promotes spontaneous calcium release in a novel computational model of rat ventricular electrophysiology." 45th Computing in Cardiology, Maastricht, Netherlands, 23-26 September 2018.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Inward rectifier current downregulation promotes spontaneous calcium release in a novel computational model of rat ventricular electrophysiology." Europhysiology, London, UK, 13-16 September 2018.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Spontaneous calcium release is promoted by inward rectifier current downregulation in a novel model of rat ventricular electrophysiology." The Heart by Numbers: Integrating Theory, Computation and Experimentation to Advance Cardiology. Berlin, Germany, 4-7 September 2018.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Mechanisms of arrhythmia triggers in heart failure predicted by a novel model of rat ventricular electrophysiology." LICAMM Early Career Science Day, Leeds, UK, 15 May 2018.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Mechanisms of arrhythmia triggers in heart failure predicted by a novel model of rat ventricular electrophysiology." 10th Multidisciplinary Cardiovascular Research Centre Retreat, Glenridding, UK, 15-16 March 2018.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Mechanisms of arrhythmia triggers in heart failure predicted by a novel model of rat ventricular electrophysiology." Future Physiology, Leeds, UK, 13-14 December 2017.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "A novel model of rat ventricular electrophysiology reveals mechanisms of spontaneous calcium release in heart failure." 44th International Congress on Electrocardiology, Portland, Oregon, USA, 24-27 June 2017.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Biophysical modelling of rat cardiac tissue electrophysiology and calcium handling: a platform for the effective integration of simulations and experiments." 25th Northern Cardiovascular Research Group Meeting, Manchester, UK, 20 April 2017.

    Stevenson-Cocks HJ, Colman MA, White E and Benson AP. "Towards detailed biophysical modelling of rat cardiac tissue electrophysiology and calcium handling." 9th Multidisciplinary Cardiovascular Research Centre Meeting, Glenridding, UK, 23-24 March 2017



  • Maxx Holmes, Ph.D Student

       

    PhD Project

    Studying the multi-scale mechanisms of atrial fibrillation, from the sub-cellular to whole-organ scales.

    Supervisors/collaborators: Mike Colman, Al Benson, Ed White, Tony Workman

    Qualificatons:

    • Bsc (Hons)   - Physics, University of Leeds, 2016
    • Msc (Hons)   - Data Science and Analytics, University of Leeds, 2017

    Profile

    I am currently a PhD researcher in the Leeds Computational Physiology Lab, as part of the Cellular Cardiology group where I currently study and produce computational models of cardiac myocytes to study fibrillatory diseases, and how tools such as machine learning, genetic algorithms and image analysis can be utilised to further research within this field.

    I originally studied BSc Physics as an undergraduate here at the University of Leeds, where I specialised in astrophysics and biophysics, before pursuing an MSc in Data Science and Analysis (University of Leeds). My BSc project looking at computational modelling of anti-chemotherapeutic drugs for an entropic analysis, and MSc project utilising machine learning to produce a dynamic population system to study the predator-prey relationships of extinct organisms through their fossil records gave me a unique cross-disciplinary skillset and understanding in applying mathematics, physics and computational science to study dynamic and complex processes, such as those within biological systems. A personal interest in cardiovascular diseases led me to my current research area where I study at the cross-section of maths, physical sciences, computing and biomedical science.

    Links: University page


Previous group members

  • Dominic Whittaker, Wellcome Trust ISSF Fellow, 2018

    Dom worked with us for a year as a Wellcome Trust ISSF Research Fellow, looking at the role of cardiac microstructure in the development and behaviour of arrhythmias.

    He now works with Gary Mirams at the University of Nottingham.

    Links: University page , Google Scholar Page


  • Eleftheria Pervolaraki, Post-doctoral Research Associate
  • Sophie Hampson, Ph.D Student, completed 2019