Dr. Sybille Krauß

Biography

Sybille Krauß studied  biotechnology at the Technische Fachhochschule Berlin until 2002. As graduate student she worked at the Max Planck Institute for Molecular Genetics and received her PhD in 2005 for her thesis „Characterization of microtubule-associated PP2A and their target proteins”. After this, she conducted research as postdoc at the Charité in the group of Prof. Susann Schweiger. Since 2010 Sybille Krauß is groupleader at DZNE in Bonn.

Research Interest

Short repetitive sequences, for example CAG trinucleotide repeats, are found in a variety of genes. These repeats are genetically instable and have the tendency to vary in length. Above a certain threshold repeat expansion is linked to disease development. Expansion of CAG repeats leads to a group of neurodegenerative diseases, the so-called CAG repeat expansion disorders. These diseases are characterized by progressive neurodegeneration. Symptoms include progressive loss of cognitive function and progressive movement disorders. Although each of the CAG repeat expansion disorders is rare, together they represent the most common form of inherited neurodegeneration. The CAG repeat can either be located in the coding region or in the untranslated region of the respective genes. When translated into protein the CAG repeat encodes for a polyglutamine stretch in the disease-causing proteins. In addition to encoding neurotoxic protein species, the CAG repeat RNA can have a toxic function itself. Structurally, mutant CAG repeat RNA differs from the physiological RNA: the expanded CAG repeats fold into characteristic hairpin structures. RNA-mediated toxicity can be explained by aberrant recruitment of RNA-binding protein to these hairpin structures. The goal of our studies is to investigate such aberrant RNA-protein interactions in CAG repeat expansion diseases and thereby identify molecular targets for the development of innovative treatment strategies. In our studies we have identified a set of proteins that aberrantly bind to mutant CAG repeats. This abnormal binding can lead to both: a loss of physiological function of the RNA-binding proteins and a gain of function of these proteins at the mutant CAG repeat RNA. For example, we have identified a protein complex, which binds to and induces aberrant translation of mRNAs containing mutant CAG repeats. Interestingly, the same protein complex promotes pathology in other diseases including sporadic neurodegenerative diseases, suggesting that deregulation of common cellular pathways may contribute to development of otherwise unrelated diseases. For our investigations we are using a broad panel of biochemical, molecular and cell biological methods.