Progress 1999

Current research areas are: evolutionary dynamics, theoretical immunology, whole heart modeling, modeling developmental processes and genome analysis Dynamical pattern formation is an important theme in evolutionary dynamics, whole heart modeling and modeling development. Evolution is an important theme not only in evolutionary dynamics but also in genomics, theoretical immunology, and the study of development.

In 1999 two dissertations on evolutionary dynamics were completed. Van Nimwegen developed a statistical dynamics formalism to describe evolutionary processes with a redundant genotype-phenotype mapping, which give rise to 'epochs'. This formalism allows an analytical treatment which generates quantitative prediction on e.g. epoch duration, bias to insensitivity to mutations and the usage of 'neutral paths'.
Pagie has studied coevolutionary processes in space. He has connected speciation, continued evolutionary change and generalized adaptation (optimization) by recognizing them as alternative ways in which information can be stored in eco-evolutionary systems, and he has shown that these may result in equivalent fitness for the individuals.

The research on theoretical immunology focussed on models for estimating T cell diversity, production, activation, and competition. Our models suggest that T cell specificity is needed to avoid auto-immune diseases, and that in general it is a good strategy for signal recognition in a noisy environment. A novel project on germinal centers is just starting.

Three dimensional organization of ventricular fibrillation is studied in a computer model of the whole heart which includes realistic ventricular geometries and cardiac anisotropy.We show that even relatively simple surface patterns are generated by a large number of three-dimensional sources of excitation (rotor filaments). We study the number and length of the filaments as a function of the heart geometry. Results show that electrical turbulence in the heart is indeed three-dimensional, although its complexity can be regarded as two-dimensional.

In modeling the development of Dictyostelium we have shown that thermo-taxis and phototaxis of the multicellular slug result from de combination of cAMP signaling (and its reduction by ammonia) and cellular adhesion which also govern earlier unicellular stages of the life-cycle. Recently, the 'culmination' of Dictyostelium modeling was reached by showing that 'culmination phase' (formation of the fruiting body) is determined by those same mechanisms.

By studying the available fully sequenced (bacterial) genomes we have demonstrated on the one hand the large variability in metabolic pathways, and on the other hand that total gene content appears to be an informative phylogenetic signal for macro evolution.

Overview of Research