Research Interests


General

Once upon a time, I began academic life as a biology student. The main reason for choosing
biology was my fascination with evolutionary processes and the complexity and diversity of
life forms. Within biology, theoretical biology, the modeling and simulation of complex biological
processes to unravel the key variables giving rise to biologically meaningful patterns and
dynamics, turned out to be my big love in science.

Modeling of cardiac arrhythmias

As a PhD student and during a large part of my postdoc my research has been focussed on
studying the causes and dynamics of ventricular cardiac arrhythmias. Cardiac arrhythmias are
disturbances in the rate and coordination of contraction of the heart that are caused by abnor-
malities in the electrical excitation wave that triggers and coordinates contraction of the cardiac
muscle cells. Therefore, to model cardiac arrhythmias, we simulate the propagation of cardiac
excitation waves. For this research I work ogether with Dr. Sasha Panfilov. Together we pioneered
the development and application of large scale, quantitative,and human specific heart models to the
study of cardiac arrhythmias. (go here for references) The models we developed are widely used
by both fellow scientists, farmaceutical researchers and students. A major insight following from
our and other studies is that heart size is not the only determinant in arrhythmia complexity, but
that action potential duration and its lower boundary of shortening in response to increases in heart
rate are also of major importance. It is commonly assumed that the dog and pig heart, because their
sizes are similar to that of the human heart, are the best model system. Our work shows that this is
not the case.

Modeling of evolutionary processes

More recently, I have returned to my old love for evolution and have started working on models of the
evolution of speciation processes and of developmental pathways, the common theme being my interest
in linking micro to macroevolutionary patterns. It is becoming clearer and clearer in biology that to
understand form, function and evolution of organisms it is important to not just consider the amount and
types of genes organisms contain but also the complex network of interactions between genes, RNA and
proteins that ultimately determines which genes are expressed when and where. However, classical evolutio-
nary models consider organisms as containing a static bag of genes whose presence determine organismal
properties in a simple, often linear fashion. Put differently, these models assume a static genetic architecture
and a linear genotype phenotype mapping. In contrast, my research focuses on the role of a flexible, evolving
genetic architecture (genome and gene regulatory network organization) and a complex genotype-phenotype
mapping in evolutionary processes. For this research I work together with Prof. Paulien Hogeweg. Recently
we showed that in models including evolving genome and network architectures and complex genotype-phenotype
mappings random mating does not prevent discrete phenotypic divergence, as is predicted by more classical
models. (go here for references) Furthermore our results suggest that genetic polymorphism may often precede
sympatric speciation.