Cardiovascular Systems Biology
Full course descriptionThe course consists of lectures and journal clubs on the following topics: 1) Cardiac ion channels and cellular electrophysiology 2) Fundamental arrhythmia mechanisms 3) Computational modeling of cardiac electrophysiology 4) Signal processing and imaging of cardiac electrophysiology 5) Clinical arrhythmia syndromes and antiarrhythmic therapies 6) Cardiac arrhythmia management in the era of complex genetics In parallel, participants will obtain hands-on research experience working on a project investigating the potential proarrhythmic consequences of ion-channel mutations using computational modeling (in Python and/or Matlab). The mathematical and programming skills needed for this research (e.g., parameter optimization techniques) will be trained during a number of computer labs. Finally, a demonstration of experimental cellular electrophysiology (patch-clamp) techniques will be given during a lab visit.
Course objectivesSince the first quantitative description of neuronal electrophysiology in the Nobel prize-winning work of Hodgkin and Huxley in the 1950s, computational and systems biology approaches have also gained increasing prominence in the field of cardiology. These approaches span spatial levels ranging from individual ion channels to the whole heart and have produced significant insight into the mechanisms of cardiac arrhythmias and improved treatment strategies. Some systems biology approaches are even actively used in clinical practice to guide management of patients. In this course, participants will explore the experimental, computational, and clinical components of cardiovascular systems biology with particular emphasis on cardiac electrophysiology and arrhythmogenesis. We will highlight the multidisciplinary nature of this topic, addressing fundamental pathophysiological concepts, computational approaches and clinical implications.
Recommended readingReferences supporting the information presented during lectures will be noted on the lecture slides and participants are strongly encouraged to employ these to obtain additional information to answer their questions and expand their knowledge on topics of interest. In addition, the following papers provide a relevant general introduction into cardiovascular systems biology: 1. Grace AA, Roden DM. Systems biology and cardiac arrhythmias. Lancet. 2012 Oct 27;380(9852):1498-508. 2. Rudy Y, Silva JR. Computational biology in the study of cardiac ion channels and cell electrophysiology. Q Rev Biophys. 2006 Feb;39 (1):57-116. 3. Heijman J, Erfanian Abdoust P, Voigt N, Nattel S, Dobrev D. Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation. J Physiol. 2016 Feb 1;594(3):537-53. 4. Trayanova NA, Chang KC. How computer simulations of the human heart can improve anti-arrhythmia therapy. J Physiol. 2016 May 1;594 (9):2483-502. 5. Viceconti M, Hunter P. The Virtual Physiological Human: Ten Years After. Annu Rev Biomed Eng. 2016 Jul 11;18:103-23. 6. Cluitmans MJ, Peeters RL, Westra RL, Volders PG. Noninvasive reconstruction of cardiac electrical activity: update on current methods, applications and challenges. Neth Heart J. 2015 Jun;23(6):301- 11. 7. Wilde AA, Behr ER. Genetic testing for inherited cardiac disease. Nat Rev Cardiol. 2013 Oct;10(10):571-83.
4 Feb 2019
5 Apr 2019
- J. Heijman
Teaching methods:Lecture(s), PBL
Assessment methods:Attendance, Written exam, Assignment