Physics of the Heart


Michael A. Colman, Ph.D.
M.R.C. Strategic Skills Research Fellow /
University Academic Fellow
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, UK
m.a.colman@leeds.ac.uk

Updates

05.01.2018 - Welcome Dom!

It is with pleasure that we welcome Dominic Whittaker to the group, as a Wellcome Trust ISSF Fellow working on modelling and mapping cardiac excitation patterns

04.10.2017 - Manuscript Accepted

Manuscript "Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator" accepted by Frontiers in Physiology - open access

27.09.2017 - Welcome Maxx!

It is with pleasure that we welcome Maxx Holmes, who is just starting his Ph.D. looking at spontaneous activity and its role in heart failure associated arrhythmia.

31.08.2017 - Manuscript Accepted

Manuscript "A Computational Model of Spatio-Temporal Cardiac Intracellular Calcium Handling with Realistic Structure and Spatial Flux Distribution from Sarcoplasmic Reticulum and T-tubules Reconstructions" accepted by PLOS Computational Biology - open access

22.05.2017 - Manuscript Accepted

Manuscript "In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis" accepted by PLOS Computational Biology - open access

17.03.2017 - Manuscript submitted

Manuscript "A Computational Model of Spatio-Temporal Cardiac Intracellular Calcium Handling with Realistic Structure and Spatial Flux Distribution from Sarcoplasmic Reticulum and T-tubules Reconstructions" submitted to PLoS Computational Biology.

01.03.2017 - Fully funded Ph.D. Opportunity

Fully funded three-year studentship offered on simulation of cardiac electrophysiology. Feel free to contact me directly for informal enquiries [Now expired]

01.03.2017 - Website Updated

Website has been updated with new content and more functionality. Enjoy!

About


Welcome to Physics of the Heart! This is an informal site hosting my research (and some teaching material coming soon).

I am a University Academic Fellow in Cardiovascular Physiology at the University of Leeds and hold an M.R.C. Strategic Skills Fellowship to study the mechanisms underlying Atrial Fibrillation.
I undertook my Masters in Theoretical Physics at the University of Manchester in 2008. This was followed by a Ph.D. in Biological Physics from 2009-2012, which was published as part of the Springer Thesis Series. I was awarded a two-year E.P.S.R.C. Doctoral Prize Fellowship following my Ph.D. and also undertook a short-term UMIP project, focusing on automated ECG analysis.

I have recently been awarded an M.R.C Strategic Skills Fellowship covering a three-year period, due for completion in summer 2018.

In June 2016, I joined the Cardiovascular Research Group at the University of Leeds as a University Academic Fellow.

My research involves constructing computational models of the heart to provide mechanistic insight into cardiac arrhythmias.

I also place high importance on outreach activities and am currently enrolled in the STEM Ambassador Scheme. I have taken part in exhibits at Manchester Science Festival and The Heart Experience (funded by BHF) . If you work with children, in particular A-level students, and would like a talk on careers in science or the link between biology and physics, please feel free to contact me.

Research

Research Group

Dr. Al Benson and I run the Leeds Computational Physiology Lab, part of the Cardiovascular Sciences Research group in the Faculty of Biological Sciences and the Multidisciplinary Cardiovascular Research Centre (MCRC). Our research focuses on dissecting physiological mechanisms in both health and disease, primarily related to cardiac arrhythmias and exercise physiology.

The group currently consists of:

  • Dr. Al Benson, PI
  • Dr. Michael Colman, PI
  • Dr. Dominic Whittaker, Wellcome Trust ISSF Fellow
  • Dr. Eleftheria Pervolaraki, Post-doctoral Research Associate
  • Harley Stevenson-Cocks, Ph.D Student
  • Sophie Hampson, Ph.D Student
  • Maxx Holmes, Ph.D Student

  • Research Interests

    My primary focus is on understanding the multi-scale mechanisms of Atrial Fibrillation, from sub-cellular flucutations to complex eletrical excitation in organ. Atrial fibrillation, or AF, is a growing epidemic and can significantly impair quality of life and even lead to sudden cardiac death, causing large strain on the healthcare system.
    Cardiovascular disease is a leading cause of morbidity and mortality in the developed world, yet current treatment strategies are sub-optimal. There is therefore a pressing need to develop greater understanding of the mechanisms underlying abnormal rhythm in the heart in order to develop more effective prevention and treatment approaches.

    Computational modelling - simulation of the electrical and mechanical activity of the heart - has become an increasingly powerful tool in the wider effort to understand, diagnose and treat cardiac disorders. In particular, computational modelling allows true multi-scale investigation, linking behaviour at the sub-cellular scale to organ scale phenomena. My research interests lie at the interface of physics and biomedical science, in the application of mathematical and physics techniques currently used for theoretical investigation to develop advanced multi-scale computational frameworks for simulation of cardiac activity.

    Funded Projects


    01.08.2015 - 31.07.2018: "In silico Investigation of the Mechanisms of Abnormal Spontaneous Excitation from Cell to Organ - Insights on the Development of Atrial Fibrillation" - Principal Investigator, Medical Research Council
    Awarded as part of the M.R.C. Strategic Skills Fellowship program (now called Skills Development Fellowship). This project focuses on using computational modelling to understand the role of sub-cellular spatio-temporal calcium dynamics in the development of spontaneous excitation at the cellular scale, and the mechanisms by which it propagates to whole-organ arrhythmogenesis in human atrial fibrillation.

    Project collaborators: Prof. Alan McKane and Dr. Tobias Galla, University of Manchester; Prof. Mark Cannel, University of Bristol; Dr. Antony Workman, University of Glasgow; Prof. Jonathan Jarvis, Liverpool John Moores University; Dr. Halina Dobryznski, University of Manchester; Dr. Oleg Aslanidi, King's College London.

    08.2017: "Detailed 3D modelling of human cardiac anatomy with emphasis on the cardiac conduction system using micro-Computer Tomography and mathematical modelling techniques - variation with ageing and heart failure" - Co-Investigator (PI: Dr. Halina Dobrzynski), British Heart Foundation

    Research Topics

    Modelling spatio-temporal calcium dynamics



    It is possible to model single cardiac cells as a point source with mean-field approximations, or as a spatially extended structure which explicitly accounts for spatio-temporal calcium cycling and microscopic, random processes within individual calcium release units (CRUs). Whereas the former are ideal for large-scale simulations, the latter can incorporate detailed, super-resolution sub-cellular imaging data and present a powerful tool to provide mechanistic insight into sub-cellular function.

    Recent experimental evidence is highlighting the importance spatio-temporal phenomena such as spontaneous calcium waves (FIG 2) and spatial calcium alternans in physiological and pathophysiological cardiac function, motivating the development of more complex and integrated spatial single cell models.


    Related publications:

    Colman MA , Pinali C, Trafford AW, Zhang H, Kitmitto A.
    "A Computational Model of Spatio-Temporal Cardiac Intracellular Calcium Handling with Realistic Structure and Spatial Flux Distribution from Sarcoplasmic Reticulum and T-tubules Reconstructions" PLoS Comp. Bio. 2017

    Colman MA , Perez Alday EA, Holden AV, Benson AP
    "Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator" Front. Physiol. 2017


    Model reduction approaches



    One limitation of detailed spatio-temporal cell models is their computational intensity; it is entirely impractical to simulate the millions of cell models required for anatomically accurate, organ-scale simulations.

    The challenge is that cardiac function is an organ-scale phenomenon with underlying mechanisms at the sub-cellular scale: we must understand the mechanisms of cardiac function at both the single cell and organ scale simultaneously, and the interaction between these scales. Therefore, it is necessary to develop approaches to integrate microscopic fluctuations into simplified and efficient cell models.


    Related publications:

    Colman MA , Perez Alday EA, Holden AV, Benson AP
    "Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator" Front. Physiol. 2017

    Colman MA , Perez Alday EA, Holden AV, Benson AP
    "Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator" Front. Physiol. 2017


    Modelling human atrial fibrillation



    My Ph.D., in Prof. Henggui Zhang's group and in collaboration with Dr. Oleg Aslanidi, investigated the role of action potential heterogeneity in the development of the rapid and irregular electrical excitation characteristic of atrial fibrillation.

    This work involved developing a family of heterogeneous cell models describing the major anatomical regions of the atria. An anatomical reconstruction of the human atria was then segmented and the model used to study the role of heterogeneity and fibre alignment in the breakdown of planar excitation waves.

    We demonstrated that substantial regional heterogeneity was sufficient to promote the development of re-entrant excitation, and that electrical remodelling associated with atrial fibrillation reduced but did not eliminate this heterogeneity, leading to an increased vulnerability to atrial fibrillation as the disorder progresses. We also indicated that short action potentials and large heterogeneity in the pulmonary vein sleeves may underlie this region's propensity for atrial fibrillation triggers.

    I continue to contribute to work in Dr. Oleg Aslanidi's lab on this topic with Dr. Marta Varela, utilising a high-resolution reconstruction of the canine atria. In a series of on-going studies, we have so far demonstrated the important role of abrupt changes in fibre angle on the breakdown of excitation waves and further highlighted the role of the pulmonary vein sleeves in the genesis of such behaviour.

    Recent work involves integration of these models with the spatio-temporal models. Details coming soon.

    Related publications:

    Colman MA , Ni H, Liang B, Schmitt N, Zhang H.
    In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis. PLoS Comp. Bio. 2017

    Varela M, Colman MA , Hancox J, Aslanidi OV.
    Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Model PLoS Comp. Bio. 2016

    Morgan R, Colman MA , Chubb H, Seemann G, Aslanidi OV.
    Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling Front. Physiol. 2016

    Colman MA, Varela M, Hancox JC, Zhang H & Aslanidi OV.
    Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model. Europace, 22 014, 16, 416-423

    Colman MA, Aslanidi OV, Kharche S, Boyett MR, Garratt CJ, Hancox JC & Zhang H.
    Pro-arrhythmogenic Effects of Atrial Fibrillation Induced Electrical Remodelling - Insights from 3D Virtual Humann Atria. J Physiol, 2013, 591, 4249-4272.

    Aslanidi OV*, Colman MA*, Varela M, Zhao J, Smaill BH, Hancox JC, Boyett MR & Zhang H.
    Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation. Interface Focus, 2013, 3

    Aslanidi OV, Al-Owais M, Benson AP, Colman MA , Garratt CJ, Gilbert SH, Greenwood JP, Holden AV, Kharche S, Kinnell E, Pervolaraki E, Plein S, Stott J & Zhang H.
    Virtual tisss ue engineering of the human atrium: Modelling pharmacological actions on atrial arrhythmogenesis Eur J Pharm Sci, 2012, 46, 209S221.

    Aslanidi OV*, Colman MA*, Stott J, Dobrzynski H, Boyett MR, Holden AV & Zhang H.
    "3D virtual human atria: a computational platform for studying clinical atrial fibrillation." Prog Biophys Mol Biol, 2011, 107, 156S168.


    Non-invasive cardiac mapping


    I also work in collaboration with Dr. Erick Andres Perez Alday and Dr. Phillip Langley, investigating approaches to attain information on cardiac excitation and repolarisation patterns non-invasively through joint modelling-experimental techniques.

    Related publications:

    Perez Alday EA, Colman MA , Langley P, Zhang H.
    Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study PLoS Comp. Bio. 2017

    Perez Alday EA*, Colman MA , Langley P, Butters TD, Higham J, Workman AJ, Hancox JC, Zhang H.
    “A new algorithm to diagnose atrial ectopic origin from multi-lead ECG systems” PLoS Comp. Bio. 2014, 11, e1004026

    Colman MA, Aslanidi OV, Stott J, Holden AV & Zhang H.
    Correlation between P-wave morphology and origin of atrial focal tachycardia - insights from realistic models of the human atria and torso.” IEEE Trans Biomed Eng, 2011, 58, 2952–2955.

    Aslanidi OV*, Colman MA*, Stott J, Dobrzynski H, Boyett MR, Holden AV & Zhang H.
    "3D virtual human atria: a computational platform for studying clinical atrial fibrillation." Prog Biophys Mol Biol, 2011, 107, 156–168.

    Peer-reviewed Journal Publications

    Colman MA , Perez Alday EA, Holden AV, Benson AP
    "Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator" Front. Physiol. 2017

    Colman MA , Pinali C, Trafford AW, Zhang H, Kitmitto A.
    "A Computational Model of Spatio-Temporal Cardiac Intracellular Calcium Handling with Realistic Structure and Spatial Flux Distribution from Sarcoplasmic Reticulum and T-tubules Reconstructions" PLoS Comp. Bio. 13(8).e1005714, 2017

    Colman MA , Ni H, Liang B, Schmitt N, Zhang H.
    In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis. PLoS Comp. Bio. 13(6).e1005587, 2017

    Perez Alday EA, Colman MA , Langley P, Zhang H.
    Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study PLoS Comp. Bio. 2017

    Varela M, Colman MA , Hancox J, Aslanidi OV.
    Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Model PLoS Comp. Bio. 2016

    Morgan R, Colman MA , Chubb H, Seemann G, Aslanidi OV.
    Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling Front. Physiol. 2016

    Colman MA, Varela M, Hancox JC, Zhang H & Aslanidi OV.
    “Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model.” Europace, 2014, 16, 416-423

    Colman MA, Aslanidi OV, Kharche S, Boyett MR, Garratt CJ, Hancox JC & Zhang H.
    “Pro-arrhythmogenic Effects of Atrial Fibrillation Induced Electrical Remodelling - Insights from 3D Virtual Human Atria.” J Physiol, 2013, 591, 4249-4272.


    Perez Alday EA*, Ni H, Zhang C, Colman MA , Gan Z, Zhang H.
    Comparison of Eletric- and Magnetic- Cardiograms Produced by Myocardial Ischemia in Models of the Human Human Ventricle and Torso PLoS Comp. Bio. 2016, 11, e01609999

    Perez Alday EA*, Colman MA , Langley P, Butters TD, Higham J, Workman AJ, Hancox JC, Zhang H.
    “A new algorithm to diagnose atrial ectopic origin from multi-lead ECG systems” PLoS Comp. Bio. 2014, 11, e1004026

    Colman MA , Castro SJ, Perez Alday EA, Hancox JC, Garratt C, Zhang H.
    “Recent progress in multi-scale models of the human atria.” Drug Discov Today: Dis Models, 2015, (In Press – Accepted Proof)

    Kharche SR, Stary T, Colman MA, Biktasheva IV, Workman AJ, Rankin AC, Holden AV, Zhang H.
    “Effects of human atrial ion remodelling by β-blocker therapy on mechanisms of AF: a computer simulation” Europace, 2014, 16, 1524-1533

    Aslanidi OV*, Colman MA*, Varela M, Zhao J, Smaill BH, Hancox JC, Boyett MR & Zhang H.
    “Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation.” Interface Focus, 2013, 3

    Aslanidi OV, Al-Owais M, Benson AP, Colman MA , Garratt CJ, Gilbert SH, Greenwood JP, Holden AV, Kharche S, Kinnell E, Pervolaraki E, Plein S, Stott J & Zhang H.
    “Virtual tissue engineering of the human atrium: Modelling pharmacological actions on atrial arrhythmogenesis.” Eur J Pharm Sci, 2012, 46, 209–221.

    Colman MA, Aslanidi OV, Stott J, Holden AV & Zhang H.
    Correlation between P-wave morphology and origin of atrial focal tachycardia - insights from realistic models of the human atria and torso.” IEEE Trans Biomed Eng, 2011, 58, 2952–2955.

    Aslanidi OV*, Colman MA*, Stott J, Dobrzynski H, Boyett MR, Holden AV & Zhang H.
    "3D virtual human atria: a computational platform for studying clinical atrial fibrillation." Prog Biophys Mol Biol, 2011, 107, 156–168.



    Books


    Colman MA.
    "Mechanisms of atrial arrhythmias - Insights from the development of a biophysically detailed model of the human atria". Springer Theses Series, ISBN 978-3-319-01643-6, 2014


    Contact

    Michael A. Colman
    Room 7.56b
    Garstang Building
    School of Biomedical Sciences
    Faculty of Biological Sciences
    University Of Leeds
    Leeds, UK
    LS2 9JT
    m.a.colman@leeds.ac.uk
    +44 (0) 113 34 30340
    Follow me on ResearchGate