Current PhD Project (Oct 2013 - Oct 2016)
My DPhil (PhD) project is in the area of Computational Cardiac Electrophysiology, with a focus on understanding the causes of atrial fibrillation (AF). Specifically, my main aim has been to investigate the role of the nNOS protein in human atrial electrophysiology, via the use of computer modelling in synergy with experimental data provided by my experimental supervisor (Prof. Barbara Casadei, Cardiovascular Medicine, Oxford).
At the start of my PhD, experiments reported a decrease in nNOS levels in atrial muscle cells from patients with AF, and nNOS inhibition in control cells triggered a behaviour associated with AF. However, the underlying mechanisms linking nNOS effects and AF were unclear. My work has focused on conducting computer simulation studies to unravel mechanisms behind nNOS action in atrial muscle cells and whole atria in humans. This has been achieved in three stages.
First, I constructed an ensemble of models mimicking cellular variability in human atrial function under control conditions, to account for significant variability in experimental recordings exhibited by different cells. Second, I used this ensemble of control computer models to investigate the relative importance of nNOS-induced ionic currents in atrial cellular function. Third, I probed the role of nNOS in modulating regional gradients in atrial electrophysiology and their role in AF generation and maintenance by means of a human whole-atria model. The overall impact of my PhD has been to shed light on ionic mechanisms underlying nNOS-mediated effects and their relation to AF from the cellular to the whole atria human levels, via a unique combination of modelling and experimental information.
Next steps - EPSRC Doctoral Prize (Jan 2017 - Jun 2017)
I have been awarded the EPSRC Doctoral Prize for a six-month research project following the completion of my PhD. During the EPSRC Doctoral Prize project, I will design and conduct in silico drug trials for atrial fibrillation. To capture patient-to-patient differences in heart function, I will construct an ensemble of human whole-atria models. The goal of this work will be to investigate the ability of in silico drug trials to explain, identify, and predict different outcomes of pharmacological therapies for AF. The project will involve collaborations with clinical and industrial institutions and is expected to have clinical and pharmaceutical applications. The simulations will be performed on Archer, UK’s national supercomputer.
Keywords: multiscale modelling; physiological variability; cardiac electrophysiology; atrial fibrillation
Journal publications (IF = Impact Factor):
- J. Graham, D. R. Allan, A. Muszkiewicz*, C. A. Morrison, S. A. Moggach, The Effect of High Pressure on MOF-5: Guest-Induced Modification of Pore Size and Content at High Pressure, Angew Chem Int Ed. 2011, 50: 11138-11141, DOI: 10.1002/anie.291104285. * first modelling author; IF=11.26
- S. Moggach, A. J. Graham, A. Muszkiewicz, C. A. Morrison, High Pressure Studies of Metal Organic Framework Materials, Int J Nanotechnol. 2012, 9: 18-22, DOI: 10.1504/IJNT.2012.044827.
- B. Rodriguez, A. Carusi, N. Abi-Gerges, R. Ariga, O. Britton, G. Bub, A. Bueno-Orovio, R. A.B. Burton, V. Carapella, L. Cardone-Noott, M. J. Daniels, M. R. Davies, S. Dutta, A. Ghetti, V. Grau, S. Harmer, I. Kopljar, P. Lambiase, H. Rong Lu, A. Lyon, A. Minchole, A. Muszkiewicz, J. Oster, M. Paci, E. Passini, S. Severi, P. Taggart, A. Tinker, J.-P. Valentin, A. Varro, M. Wallman, X. Zhou, Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop. Europace 2015, DOI: http://dx.doi.org/10.1093/europace/euv320. IF=3.67
- S. N. Reilly, X. Liu, R. Carnicer, A. Recalde, A. Muszkiewicz*, R. Jayaram, M. C. Carena, M. Stefanini, N. C. Surdo, R. Wijesurenda, O. Lomas, C. Ratnatunga, R. Sayeed, G. Krasopoulos, T. Rajakumar, A. Bueno-Orovio, S. Verheule, T. A. Fulga, B. Rodriguez, U. Schotten, B. Casadei, Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase. Sci Transl Med. 2016, 8 (340), 340ra74, DOI: 10.1126/scitranslmed.aac4296. * first modelling author; IF=15.84
- A. Muszkiewicz, O. J. Britton, K. Burrage, A. Carusi, P. Gemmell, E. Passini, C. Sánchez, X. Zhou, A. Bueno-Orovio, T. A. Quinn, B. Rodriguez, Variability in Cardiac Electrophysiology: Using Experimentally-Calibrated Populations of Models to Move Beyond the Single Virtual Physiological Human Paradigm. Prog Biophys Mol Biol. 2016, 120: 115-127. DOI: 10.1016/j.pbiomolbio.2015.12.002. IF=2.27
- A. Muszkiewicz, A. Bueno-Orovio, X. Liu, B. Casadei, B. Rodriguez, Experimentally-calibrated populations of human atrial electrophysiological models mimic cell-to-cell variability in control human atrial function (in submission).
- A. Muszkiewicz, A. Bueno-Orovio, X. Liu, J. F. Rodriguez, B. Casadei, B. Rodriguez, The role of nNOS-induced changes in atrial function using a combined in silico and experimental approach (in preparation).
- D. Millar, D. Allan, L. Cocker, A. Cumming, C. Henderson, A. Mackay, H. Maynard-Casely, A. Muszkiewicz, I. Oswald, C. R. Pulham, Co-Crystallization of Energetic Materials: A Step Towards Tailored Munitions?, Proc. 14th NTREM. 2011, 298-304.
- A. Muszkiewicz, A. Bueno-Orovio, X. Liu, B. Casadei, B. Rodriguez, Constructing Human Atrial Electrophysiological Models Mimicking a Patient-Specific Cell Group, Comput Cardiol. 2014, 41: 761-764.
- A. Bueno-Orovio, O. Britton, A. Muszkiewicz, B. Rodriguez. Cardiac Modelling. In Encyclopaedia of Cell Biology, Vol 4, Waltham, MA: Academic Press, 2016, 86-94.
- 2016 Winner of the Research Spotlight Competition at the 12th London Hopper Colloquium
- 2016 EPSRC Doctoral Prize - “The purpose of the EPSRC Doctoral Prize scheme is to help universities [...] improve retention of the very best students in research careers.”
- 2014 Successful bid to Oxford University Vice-Chancellor’s Diversity Fund in support of OxFEST’s conference ‘Postcards from the Future: Rewriting the Script for Women in STEM’
- 2014 Honourable Mention (Semi-Finalist) in the Rosanna Degani Young Investigator Award Competition at the Computing in Cardiology Conference
- 2013 Travel Scholarship & Best Poster Prize at the Summer School ‘ab initio Molecular Dynamics for Biomolecules’
- 2012 Chemical Physics Prize for Outstanding Academic Achievement during undergraduate studies
- 2010 Chemical Physics Class Medal & the Gillies Prize awarded to the top 3rd year student
- 2009 Chemistry Class Medal and the Class of ’59 Prize awarded to the top 2nd year student
- 2009 Pre-Honours Certificate of Merit awarded to exceptional students in the School of Physics
- 2009 Oxford University Press Achievement in Chemistry Prize awarded to the top Chemistry student
- 2009 GlaxoSmithKline/Procter&Gamble Prize for the top result in laboratory work
- 2012-2016 Full EPSRC doctoral scholarship awarded for the DPhil. programme at Oxford University
- 2009-2012 Three Scholarships from the President of the City of Zabrze (Poland) for academic merit
- 2010-2011 Research Scholarship funded by Asst. Prof. L. Y. Chew for the research project at Nanyang Technological University, Singapore
- 2009-2011 Two EPSRC Scholarships, two College Vacation Scholarships, and British Association Travel Fund Grant for summer research projects in the UK and Singapore
2013 - 2016 PhD (DPhil) Computer Science Department, University of Oxford, UK
2012 - 2013 Systems Biology Doctoral Training Centre, St John's College, University of Oxford, UK
2007 - 2012 Master of Chemical Physics (Honours), School of Chemistry, University of Edinburgh, UK
2010 - 2011 International exchange student (research programme), Nanyang Technological University, Singapore