I am fascinated by the tremendous biological diversity in nature and especially interested in the never ending dynamics of host-parasite co-evolution and the molecular mechanisms that have evolved in vertebrate hosts to resist their pathogens. I am intrigued by the fact that hosts can cope with the vast spectrum of pathogens that they face in their natural environment, all of which are constantly evolving new tricks and tweaks to best exploit their host's resources. Even intruders that they have never encountered before are recognized as foreign and fought against.
In vertebrates - apart from the innate immune system as a first line of defense - the backbone of the ability to recognize foreign, or more precisely, non-self antigens of invading pathogens is the Major Histocompatibility Complex (MHC). MHC molecules present these antigens at the cell surface and thus play a critical part in the initiation of an adaptive immune response. However, every individual can only carry a restricted number of different MHC alleles and is therefore vitally dependent on having the most advantageous genotype, i.e. the allele combination that guarantees the broadest antigen presentation of the predominant pathogens. The MHC region, in fact, exhibits some of the highest polymorphism in the vertebrate genome, comprising a large number of alleles and excessive allele divergence at the population level as well as high heterozygosity and a variable number of loci at the individual level. This polymorphism evolved and has been maintained by balancing selection, presumably driven by the never-ending selection of coevolving pathogens.
Over the years, I have studied several model and non-model organisms to unravel the molecular depths of this astounding gene complex and the evolutionary forces maintaining its polymorphism. Associations of MHC diversity and fitness parameters observed in natural populations were complemented by experimental approaches in the lab. This work has contributed to our general understanding of the evolution of MHC genes, but also opened up new avenues of research and is still ongoing. In addition, I have recently started to apply some of the new insights obtained from work with natural populations and non-model organisms to human populations. Here I am using computational tools to investigate the evolutionary significance of HLA (the human MHC) diversity at the population level and at the individual level. This work is greatly facilitated by the advent of next generation sequencing data and further inspired by the growing attention to evolutionary medicine.