The Institute of Experimental Pathology (acting director: Prof. M. Alexander Schmidt), formerly directed by Prof. Juergen Brosius, performs basic research in Molecular Genetics and Evolution. (For CV and full publication list of Prof. Brosius click here),
1) Our primary focus is on non-protein coding RNAs (npcRNAs) with emphasis on those preferentially expressed in the brain, ranging from discovery to function. This includes gene deletions (the epigenetically regulated MBII-85 RNA cluster) leading to mouse models of Prader-Willi-Syndrome (a neurodevelopmental disease), as well as certain forms of epilepsy that are mediated by dysregulation of protein biosynthesis near synapses and hyperexcitability due to absence of BC1 RNA. Wherever possible, we use transgenic mouse models ("in vivo veritas") in diverse studies, such as the regulation of neuronal expression of npcRNAs, sub-cellular transport of RNAs into neuronal processes and functional compensation of gene-deleted animal models.
2) From such simple beginnings of a protocell consisting of a small number of RNA molecules, we are still able to learn lessons on how modern genomes and genes evolve(d). The conversion of RNA to DNA via retroposition remains a major factor in providing raw material for future (nondirected) evolvability. Much of this process generates superfluous DNA. Yet, occasionally new modules of existing genes can be, by chance exapted (recruited) from such previously non-functional sequences.
More recently, culminating in the "sales"-effort of the ENCODE consortium, the pendulum has almost swung towards the opposite extreme. This falsely implies that almost 80% of the human genome and, in analogy, that almost every chunk of transcribed RNA is functional (see cartoon). For an excellent assessment of this recent excess see Graur et al. (2013) and for the noisy transcriptome see this paper.
We also use retroposed elements to infer phylogenetic relationships in vertebrates, chiefly in mammals and birds.
Also, the academic content that we present in our teaching relies heavily on evolutionary thought. Apart from a better understanding of how cells and organisms work, it provides us with valuable tools to understand the evolution of genomes and genes. For medical students, it addresses the question "why we get sick" in a fundamental way. Finally, many bioethical questions posed by our growing capabilities in medical technology, such as gene therapy, assisted reproduction etc. are rendered more tangible “in the light of evolution”.
Innovative analogies and radical thinking should free students from the restrictions and chains of much of their previous scholastic education. Likewise, evolutionary thought is potentially decisive in complicated patent disputes in the areas of life and biomedical sciences including biotechnology and RNA biology.