Jonas van den Brink successfully defended his thesis

Main research findings

The heart is a vital organ composed of billions of muscle cells. The micro-anatomical structures within these cells are specialized to produce force rapidly and reliably. Especially important are tiny regions in the cell named dyads, which are crucial for coupling electrical excitation of the cell and its contraction. With disease, these dyads become disrupted and broken down, leading to a weaker contraction. However, due to their incredibly small size, it has been hard to quantify how structures change and how changed anatomical architecture affects function. Computational modeling and analysis, therefore, plays a critical role in furthering our understanding of structure-function relationships in cardiac cells, which in turn is a necessary step towards better treatment for cardiac disease.

In this work, we have developed new tools and techniques for imaging and analyzing cardiac dyads using super-resolution microscopy. This has allowed us to better quantify and understand how dyads change with disease. From microscopy data we also created digital geometries, enabling us to simulate the function of both healthy and disrupted dyads using mathematical modeling. This yielded new insights into structure-function relationships in contraction of the heart, and allowed us to better understand how disease-driven remodeling affects cardiac function.

The work has been conducted at Simula Research Laboratory and the University of Oslo.

Prior to the defence, Jonas van den Brink presented his trial lecture"Electrodiffusion modeling of neurons: concepts, models and key challenges".

The PhD defence and trial lecture were fully digital.

Adjudication committee

• Senior Investigator Michael Stern, National Institute of Aging, USA
• Director Eva Rog-Zielinska, University of Freiburg, Germany
• Professor Ole Christian Lingjærde, Department of Informatics, University of Oslo, Norway

Supervisors

• Adjunct Assistant Professor Andrew G. Edwards, Department of Pharmacology, University of California Davis
• Researcher William E. Louch, Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo
• Professor Aslak Tveito, Department of Informatics, University of Oslo, Norway /Simula Research Laboratory
• Associate professor Glenn Terje Lines,Department of Computational Physiology, Simula Research Laboratory
• Professor Andrew D. McCulloch, Department of Bioengineering, University of California San Diego

Chair of defence

• Professor Andreas Austeng, Department of Informatics, University of Oslo, Norway