Denis Noble

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. doi request reprint Genes and causation
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Philos Trans A Math Phys Eng Sci 366:3001-15. 2008
  2. pmc Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing
    Gary R Mirams
    Computational Biology, Department of Computer Science, University of Oxford, Oxford, UK
    Br J Pharmacol 167:932-45. 2012
  3. pmc Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk
    Gary R Mirams
    Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford, OX1 3PT, UK
    Cardiovasc Res 91:53-61. 2011
  4. pmc Ca²⁺-induced delayed afterdepolarizations are triggered by dyadic subspace Ca2²⁺ affirming that increasing SERCA reduces aftercontractions
    Martin Fink
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Am J Physiol Heart Circ Physiol 301:H921-35. 2011
  5. doi request reprint Considerations for the use of cellular electrophysiology models within cardiac tissue simulations
    Jonathan Cooper
    Oxford University Computing Laboratory, University of Oxford, Wolfson Building, Parks Road, Oxford OX13QD, UK
    Prog Biophys Mol Biol 107:74-80. 2011
  6. pmc Modeling cardiac ischemia
    Blanca Rodriguez
    Oxford University Computing Laboratory, Wolfson Building, Parks Road, Oxford, UK
    Ann N Y Acad Sci 1080:395-414. 2006
  7. ncbi request reprint Commentary: physiology is the logic of life
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Jpn J Physiol 54:509-10. 2004
  8. pmc Could there be a Synthesis between Western and Oriental Medicine, and with Sasang Constitutional Medicine in Particular?
    Denis Noble
    CBE, FRS, Department of Physiology, Anatomy and Genetics Parks Road, Oxford OX1 3PT, UK
    Evid Based Complement Alternat Med 6:5-10. 2009
  9. ncbi request reprint Computational models of the heart and their use in assessing the actions of drugs
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
    J Pharmacol Sci 107:107-17. 2008
  10. ncbi request reprint Systems biology and the heart
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Biosystems 83:75-80. 2006

Detail Information

Publications54

  1. doi request reprint Genes and causation
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Philos Trans A Math Phys Eng Sci 366:3001-15. 2008
    ..Because it can solve the 'genetic differential effect problem', modelling of biological function has an essential role to play in unravelling genetic causation...
  2. pmc Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing
    Gary R Mirams
    Computational Biology, Department of Computer Science, University of Oxford, Oxford, UK
    Br J Pharmacol 167:932-45. 2012
    ..In this paper, we review the current use of biophysically detailed mathematical models of cardiac myocyte electrical activity in drug safety testing, and suggest future directions to employ the full potential of this approach...
  3. pmc Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk
    Gary R Mirams
    Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford, OX1 3PT, UK
    Cardiovasc Res 91:53-61. 2011
    ..In this study, we investigate whether a simulated evaluation of multi-channel effects could be used to improve this early prediction of TdP risk...
  4. pmc Ca²⁺-induced delayed afterdepolarizations are triggered by dyadic subspace Ca2²⁺ affirming that increasing SERCA reduces aftercontractions
    Martin Fink
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Am J Physiol Heart Circ Physiol 301:H921-35. 2011
    ....
  5. doi request reprint Considerations for the use of cellular electrophysiology models within cardiac tissue simulations
    Jonathan Cooper
    Oxford University Computing Laboratory, University of Oxford, Wolfson Building, Parks Road, Oxford OX13QD, UK
    Prog Biophys Mol Biol 107:74-80. 2011
    ..Such information can be added as metadata, but agreement is needed on the terms to use, including development of appropriate ontologies, if reliable automated use of CellML models is to become common...
  6. pmc Modeling cardiac ischemia
    Blanca Rodriguez
    Oxford University Computing Laboratory, Wolfson Building, Parks Road, Oxford, UK
    Ann N Y Acad Sci 1080:395-414. 2006
    ..This article aims to review and summarize the results of these studies and to emphasize the role of computer simulations in improving the understanding of ischemia-related arrhythmias and how to efficiently terminate them...
  7. ncbi request reprint Commentary: physiology is the logic of life
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Jpn J Physiol 54:509-10. 2004
  8. pmc Could there be a Synthesis between Western and Oriental Medicine, and with Sasang Constitutional Medicine in Particular?
    Denis Noble
    CBE, FRS, Department of Physiology, Anatomy and Genetics Parks Road, Oxford OX1 3PT, UK
    Evid Based Complement Alternat Med 6:5-10. 2009
    ....
  9. ncbi request reprint Computational models of the heart and their use in assessing the actions of drugs
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
    J Pharmacol Sci 107:107-17. 2008
    ..The models have also been incorporated into tissue and organ models that enable arrhythmia to be modelled also at these levels. Work at these levels can reproduce both re-entrant arrhythmia and fibrillation...
  10. ncbi request reprint Systems biology and the heart
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Biosystems 83:75-80. 2006
    ..I use models of the heart to demonstrate that we can now go all the way from individual genetic information (on mutations, for example) to exploring the consequences at a whole organ level...
  11. ncbi request reprint Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study
    Gentaro Iribe
    Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK
    Philos Trans A Math Phys Eng Sci 364:1107-33. 2006
    ....
  12. ncbi request reprint Resistance of cardiac cells to NCX knockout: a model study
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
    Ann N Y Acad Sci 1099:306-9. 2007
    ..The effects can therefore be expected to be species-specific, and it is not possible to extrapolate the mouse results to those that may occur in the Guinea pig or human...
  13. ncbi request reprint Systems biology, the Physiome Project and oriental medicine
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
    J Physiol Sci 59:249-51. 2009
    ..Second, there are major problems of translation and interpretation to be tackled. Exploring the full semantic frame of the oriental concepts will be necessary before mapping to concepts in western medicine can be useful...
  14. pmc From the Hodgkin-Huxley axon to the virtual heart
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Parks Road, Oxford, OX1 3PT, UK
    J Physiol 580:15-22. 2007
    ..With over 40 years of interaction between simulation and experiment, the models are now sufficiently refined to begin to be of use in drug development...
  15. ncbi request reprint Dimensionality in cardiac modelling
    Alan Garny
    Department of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Prog Biophys Mol Biol 87:47-66. 2005
    ..The ideal model will be as simple as possible and as complex as necessary for the particular question raised...
  16. ncbi request reprint Modeling the heart--from genes to cells to the whole organ
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Science 295:1678-82. 2002
    ..This review illustrates this development in the case of the heart. Systems physiology of the 21st century is set to become highly quantitative and, therefore, one of the most computer-intensive disciplines...
  17. pmc Unraveling the genetics and mechanisms of cardiac arrhythmia
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, United Kingdom
    Proc Natl Acad Sci U S A 99:5755-6. 2002
  18. ncbi request reprint The rise of computational biology
    Denis Noble
    Department of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Nat Rev Mol Cell Biol 3:459-63. 2002
    ..So, why has all this happened so suddenly?..
  19. ncbi request reprint Influence of Na/Ca exchange stoichiometry on model cardiac action potentials
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Ann N Y Acad Sci 976:133-6. 2002
    ..The K(d) required for such regulation is consistent with current experimental estimates of this parameter...
  20. ncbi request reprint Simulation of Na/Ca exchange activity during ischemia
    Denis Noble
    University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, UK
    Ann N Y Acad Sci 976:431-7. 2002
    ..If such oscillations play a role in acute ischemic arrhythmias, then block of Na/Ca exchange may not be therapeutic...
  21. ncbi request reprint The heart cell in silico: successes, failures and prospects
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Novartis Found Symp 247:182-94; discussion 194-7, 198-206, 244-52. 2002
    ..The insights gained are evident in the most recent developments in this field, both experimental and theoretical. The prospects for the future are discussed...
  22. ncbi request reprint Will genomics revolutionise pharmaceutical R&D?
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Trends Biotechnol 21:333-7. 2003
    ..The major obstacle to achieving this will be obtaining the relevant experimental data at levels higher than genomics and proteomics...
  23. ncbi request reprint One-dimensional rabbit sinoatrial node models: benefits and limitations
    Alan Garny
    Department of Physiology, University of Oxford, Oxford, United Kingdom
    J Cardiovasc Electrophysiol 14:S121-32. 2003
    ..Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function...
  24. pmc Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking
    Ming Lei
    University Laboratory of Physiology, University of Oxford, OX1 3PT, UK
    J Physiol 559:835-48. 2004
    ..1) and cardiac Nav1.5 isoforms are involved in pacemaking, although the cardiac Nav1.5 isoform alone is involved in the propagation of the action potential from the SA node to the surrounding atrial muscle...
  25. ncbi request reprint Modeling the heart
    Denis Noble
    University Laboratory of Physiology Oxford OX1 3PT, UK
    Physiology (Bethesda) 19:191-7. 2004
    ..The first models of calcium balance were made in the 1980s and have now reached a high degree of physiological detail. During the 1990s, these cell models were incorporated into anatomically detailed tissue and organ models...
  26. ncbi request reprint The role of the Na+/Ca2+ exchangers in Ca2+ dynamics in ventricular myocytes
    Anna A Sher
    Computational Biology Group, Computing Laboratory, Department of Physiology, University of Oxford, UK
    Prog Biophys Mol Biol 96:377-98. 2008
    ..Our modelling results support the claim that NCX regulates the local control of Ca2+ and provide a powerful tool for future investigations of the control of sarcoplasmic reticulum (SR) Ca2+ release under pathological conditions...
  27. pmc How the Hodgkin-Huxley equations inspired the Cardiac Physiome Project
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK
    J Physiol 590:2613-28. 2012
    ..This article reviews the development of models representing almost all cell types in the heart, many different species, and the software tools that have been created to facilitate the cardiac Physiome Project...
  28. doi request reprint Competing oscillators in cardiac pacemaking: historical background
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Oxford University, Parks Rd, Oxford OX1 3PT, United Kingdom
    Circ Res 106:1791-7. 2010
    ..The reverse seems to be true only in pathological conditions. Studies from tissue-level work and on the development of the heart also provide valuable insights into the integrative action of the cardiac pacemaker...
  29. doi request reprint Prologue: mind over molecule: activating biological demons
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Oxford University, Parks Road, Oxford OX1 3PT UK
    Ann N Y Acad Sci 1123:xi-xix. 2008
    ..The principles outlined are illustrated with examples from cardiac and other aspects of physiology and biochemistry...
  30. doi request reprint Pharmacodynamic effects in the cardiovascular system: the modeller's view
    Martin Fink
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
    Basic Clin Pharmacol Toxicol 106:243-9. 2010
    ....
  31. ncbi request reprint Modelling the heart: insights, failures and progress
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Bioessays 24:1155-63. 2002
    ..It is the iterative interaction between experiment and simulation that is important. Examples are given where this process has been instrumental in some of the major advances in the field...
  32. doi request reprint Physiology is rocking the foundations of evolutionary biology
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Oxford, UK
    Exp Physiol 98:1235-43. 2013
    ..The 21st century can look forward to a new synthesis that will reintegrate physiology with evolutionary biology. ..
  33. doi request reprint A biological relativity view of the relationships between genomes and phenotypes
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Prog Biophys Mol Biol 111:59-65. 2013
    ..The article concludes by showing that far from breaking the supervenience principle, downward causation requires that it should be obeyed...
  34. pmc Neo-Darwinism, the modern synthesis and selfish genes: are they of use in physiology?
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK
    J Physiol 589:1007-15. 2011
    ..e. the 'success' in the gene pool that is supposed to be attributable to the 'selfish' property. It is not a physiologically testable hypothesis...
  35. pmc The Cardiac Physiome: perspectives for the future
    James Bassingthwaighte
    Department of Physiology, Anatomy and Genetics, Oxford, UK
    Exp Physiol 94:597-605. 2009
    ..Despite the enormity of the challenge, which is certainly greater than that facing the pioneers of the human genome project 20 years ago, there is reason for optimism that real and accelerating progress is being made...
  36. ncbi request reprint Role of pacemaking current in cardiac nodes: insights from a comparative study of sinoatrial node and atrioventricular node
    Jie Liu
    Department of Physiology, University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, UK
    Prog Biophys Mol Biol 96:294-304. 2008
    ..The computer simulation shows that the difference in the intrinsic CL could explain the difference in response to If blocking in these two cardiac nodes...
  37. ncbi request reprint Computational physiology and the Physiome Project
    Edmund J Crampin
    Centre for Mathematical Biology, Mathematical Institute, University of Oxford, 24 29 St Giles, Oxford, OX1 3LB, UK
    Exp Physiol 89:1-26. 2004
    ..Integrative physiology is central to the interpretation of genomic and proteomic data, and is becoming a highly quantitative, computer-intensive discipline...
  38. doi request reprint Successes and failures in modeling heart cell electrophysiology
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK
    Heart Rhythm 8:1798-803. 2011
    ..We often learn as much from the failures as from the successes of mathematical models. It is the iterative interaction between experiment and simulation that is important...
  39. doi request reprint CELLULAR OPEN RESOURCE (COR): current status and future directions
    Alan Garny
    Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK
    Philos Trans A Math Phys Eng Sci 367:1885-905. 2009
    ....
  40. ncbi request reprint Claude Bernard, the first systems biologist, and the future of physiology
    Denis Noble
    Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK
    Exp Physiol 93:16-26. 2008
    ..The principles outlined are illustrated with examples from various aspects of physiology and biochemistry. Applying and developing these principles should form a major part of the future of physiology...
  41. pmc Biophysics and systems biology
    Denis Noble
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK
    Philos Trans A Math Phys Eng Sci 368:1125-39. 2010
    ..We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights...
  42. doi request reprint Is it time for in silico simulation of drug cardiac side effects?
    Gary R Mirams
    Department of Computer Science, University of Oxford, Oxford, United Kingdom
    Ann N Y Acad Sci 1245:44-7. 2011
    ..Cardiac simulation is used to integrate information on drug action to predict side effects on the whole heart. Could simulation begin to replace animal models?..
  43. doi request reprint A global sensitivity tool for cardiac cell modeling: Application to ionic current balance and hypertrophic signaling
    Anna A Sher
    Department of Physiology, Anatomy and Genetics, University of Oxford, UK
    Conf Proc IEEE Eng Med Biol Soc 2010:1498-502. 2010
    ..Such profiling suggests new avenues for development of methodologies to predict drug action effects in cardiac cells...
  44. pmc Role of Na/Ca exchange and the plasma membrane Ca2+-ATPase in cell function. Conference on Na/Ca exchange
    Denis Noble
    Department of Physiology, Oxford University, Parks Road, Oxford OX1 3PT, UK
    EMBO Rep 8:228-32. 2007
  45. ncbi request reprint 'In silico' simulation of biological processes. Chair's introduction
    Denis Noble
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Novartis Found Symp 247:1-3. 2002
  46. ncbi request reprint Functional significance of Na+/Ca2+ exchangers co-localization with ryanodine receptors
    Anna A Sher
    Computational Biology Group, University of Oxford Computing Laboratory, Wolfson Building, Parks Road, Oxford OX1 3QD, Oxford, UK
    Ann N Y Acad Sci 1099:215-20. 2007
    ..g., impaired LCCs, local NCXs become an enhancer of sarcoplasmic reticulum release. Under such conditions incorporation of local NCXs is critical to accurately capture mechanisms of excitation-contraction coupling...
  47. ncbi request reprint Ascending aortic stenosis selectively increases action potential-induced Ca2+ influx in epicardial myocytes of the rat left ventricle
    Tilmann Volk
    Institut fur Zellulare und Molekulare Physiologie, Friedrich Alexander Universitat Erlangen Nurnberg, Waldstrasse 6, 91054 Erlangen, Germany
    Exp Physiol 90:111-21. 2005
    ..In conclusion, AS significantly increased AP-induced Ca2+ influx in epicardial but not in endocardial myocytes of the rat left ventricle...
  48. ncbi request reprint Contributions of inwardly rectifying K+ currents to repolarization assessed using mathematical models of human ventricular myocytes
    Martin Fink
    Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0412, USA
    Philos Transact A Math Phys Eng Sci 364:1207-22. 2006
    ....
  49. ncbi request reprint Modelling of calcium handling in airway myocytes
    Etienne Roux
    Laboratoire de Physiologie Cellulaire Respiratoire, INSERM E 356, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France
    Prog Biophys Mol Biol 90:64-87. 2006
    ..The development of such models of airway myocytes is important for the understanding of the cellular mechanisms of airway reactivity and their possible modulation by pharmacological agents...
  50. ncbi request reprint Analysis of the chronotropic effect of acetylcholine on sinoatrial node cells
    Henggui Zhang
    School of Biomedical Sciences, University of Leeds, United Kingdom
    J Cardiovasc Electrophysiol 13:465-74. 2002
    ..The ionic basis underlying the negative chronotropic effect of acetylcholine (ACh) on sinoatrial (SA) node cells is unresolved and controversial. In the present study, mathematical modeling was used to address this issue...
  51. ncbi request reprint Editorial: computational modelling of cell & tissue processes & function
    Michael N Moore
    J Mol Histol 35:655-8. 2004
    ....
  52. ncbi request reprint Modeling of molecular and cellular mechanisms involved in Ca2+ signal encoding in airway myocytes
    Marko Marhl
    University of Maribor, Department of Physics, Koroska cesta 160, SI 2000 Maribor, Slovenia
    Cell Biochem Biophys 46:285-302. 2006
    ..Modeling the mechanisms responsible for the decoding of calcium signals is developed in a lesser extent; however, the most recent theoretical studies are briefly presented in relation with the known experimental results...
  53. ncbi request reprint Contributions of HERG K+ current to repolarization of the human ventricular action potential
    Martin Fink
    Department of Medicine, University of California San Diego, San Diego, CA, USA
    Prog Biophys Mol Biol 96:357-76. 2008
    ..Our overall goal is to understand the genesis of the T-wave of the human electrocardiogram...
  54. ncbi request reprint Knowledge capture and the responsibility: past and present
    Nic Smith
    Prog Biophys Mol Biol 96:1-2. 2008