Dr. Sybille Krauß

Group Leader

German Center for Neurodegenerative Diseases (DZNE)
Sigmund-Freud-Str. 27 
53127 Bonn

sybille.krauss(at)dzne.de
+49 (0) 228 / 43302-555 (Büro)
+49 (0) 228 / 43302-684 (Secretary)

Group members

Name Telephone
Nancy El Deiry, Assistant +49 (0)228 / 43302-684
Judith Schilling, Ph.D. Student +49 (0)228 / 43302-558
Dr. Frank Matthes, Postdoc +49 (0)228 / 43302-559
Stephanie Weber, Technical Assistant +49 (0)228 / 43302-557

Publications

 

The E3-ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu.

Susann Schweiger, Stephanie Dorn, Melanie Fuchs, Andrea Köhler, Eva-Christina Müller, Erich Wanker, Rainer Schneider, Sybille Krauß. JBC, 2014; DOI: 10.1074/jbc.M113.541219. 

Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies.

Jens Wagner, Sybille Krauss, Song Shi, Sergey Ryazanov, Julia Steffen, Carolin Miklitz, Andrei Leonov, Alexander Kleinknecht, Bettina Göricke, Jochen H. Weishaupt, Daniel Weckbecker, Anne M. Reiner, Wolfgang Zinth, Johannes Levin, Dan Ehninger, Stefan Remy, Hans A. Kretzschmar, Christian Griesinger, Armin Giese, Martin Fuhrmann. Acta Neuropathol (2015) 130:619–631. DOI 10.1007/s00401-015-1483-3.

Molecular View of Ligands Specificity for CAG Repeats in Anti-Huntington Therapy.

Anna Bochicchio, Giulia Rossetti, Oriana Tabarrini, Sybille Krauβ, and Paolo Carloni. J. Chem. Theory Comput. 2015; DOI: 10.1021/acs.jctc.5b00208.

Regulation of mRNA translation by MID1: a common mechanism of expanded CAG repeat RNAs.

Nadine Griesche, Judith Schilling, Stephanie Weber, Marlena Rohm, Verena Pesch, Frank Matthes, Georg Auburger and Sybille Krauss. Front. Cell. Neurosci. 2016; doi: 10.3389/fncel.2016.00226.

Mechanisms of RNA-Induced Toxicity in Diseases Characterised by CAG Repeat Expansions.

Judith Schilling, Nadine Griesche, Sybille Krauß. eLS. John Wiley & Sons, Ltd: Chichester (2016) DOI:10.1002/9780470015902.a0026464.

The MID1 protein is a central player during development and in disease.

Jennifer Winter, M. Felicia Basilicata, Marc P. Stemmler, Sybille Krauss. Front Biosci (Landmark Ed) (2016); 21:664-82.

The anti-diabetic drug metformin reduces BACE1 protein levels by interfering with the MID1 complex.

Hettich MM, Matthes F, Ryan DP, Griesche N, Schröder S, Dorn S, Krauβ S, Ehninger D. PLoS One. 2014 Jul 15;9(7):e102420. doi: 10.1371/journal.pone.0102420. eCollection 2014.

A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signalling.

Köhler A, Demir U, Kickstein E, Krauss S, Aigner J, Aranda-Orgillés B, Karagiannidis AI, Achmüller C, Bu H, Wunderlich A, Schweiger MR, Schaefer G, Schweiger S, Klocker H, Schneider R. Mol Cancer. 2014 Jun 9;13(1):146.  

Metformin lowers Ser-129 phosphorylated α-synuclein levels via mTOR-dependent protein phosphatase 2A activation.

BI Pérez-Revuelta, MM Hettich, A Ciociaro, C Rotermund, PJ Kahle, S Krauss and DA Di Monte. Cell Death Dis. 2014 May 8;5:e1209. doi: 10.1038/cddis.2014.175  

Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins

Sybille Krauss and Ina Vorberg. International Journal of Cell BiologyVolume 2013, Article ID 704546, dx.doi.org/10.1155/2013/704546 

Mechanisms of RNA-induced toxicity in CAG repeat disorders

R Nalavade, N Griesche, DP Ryan, S Hildebrand and S Krauß. Cell Death and Disease (2013) 4, e752; doi:10.1038/cddis.2013.276; published online 1 August 2013 

Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.

Krauss S, Griesche N, Jastrzebska E, Chen C, Rutschow D, Achmüller C, Dorn S, Boesch SM, Lalowski M, Wanker E, Schneider R, Schweiger S. Nat Commun. 2013;4:1511. doi: 10.1038/ncomms2514. 

FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.

J Araujo, P Breuer, S Dieringer, S Krauss, S Dorn, K Zimmermann, A Pfeifer, T Klockgether, U Wuellner, BO Evert, Human Molecular Genetics, 2011 Aug 1, 20 (15) art. no. ddr197, pp 2928-2941. Epub 2011 May2.

Control of mTORC1 signaling by the Opitz syndrome protein MID1.

Liu E, Knutzen CA, Krauss S, Schweiger S, Chiang GG, Proc Natl Acad Sci U S A. 2011 May 24;108(21):8680-5. Epub 2011 May 9.

Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.

E Kickstein, S Krauss, P Thornhill, D Rutschow, R Zeller, J Sharkey, R Williamson, M Fuchs, A Köhler, H Glossmann, R Schneider, C Sutherland, S Schweiger; PNAS. 2010 Nov 22; doi:10.1073/pnas.0912793107.

Point mutations in GLI3 lead to misregulation of its subcellular localization.

S Krauss, J So, M Hambrock, A Köhler, M Kunath, C Scharff, M Wessling, KH Grzeschik, R Schneider & S Schweiger, PLOS ONE 2009; 4(10):e7471.

PP2A and rapamycin regulate the nuclear localization and activity of the transcription factor GLI3.

Sybille Krauß, John Foerster, Rainer Schneider, Susann Schweiger, Cancer research 2008;68(12):4658–65.

PPAR delta is a type 1 interferon target gene and inhibits apoptosis in T cells.

Nadya al Yacoub, Malgorzata Romanowska, Sybille Krauss, Susann Schweiger, John Foerster, Journal of Investigative Dermatology 2008 Aug;128(8):1940-9.

Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing.

Winter J, Lehmann T, Krauss S, Trockenbacher A, Kijas Z, Foerster J, Suckow V, Yaspo ML, Kulozik A, Kalscheuer V, Schneider R, Schweiger S, Human Genetics 2004 May;144(6):541-52.

MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.

Trockenbacher A, Suckow V, Foerster J Winter J, Krauss S, Ropers HH, Schneider R, Schweiger S, Nature Genetics 2001 Nov;29(3):287-94.

Curriculum vitae

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.


Areas of investigation/research focus

Schematic representation of a neuron showing mechanisms of RNA-induced toxicity. Mutant CAG repeat RNA encodes neuro-toxic protein-species and can capture RNA-binding proteins, leading either to a gain of aberrant function or a loss of physiological function of these RNA-binding proteins. Source: DZNE / AG Krauss
Schematic representation of a neuronClick on the magnifying glass for a large image.

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.

Primary cortical neuron expressing GFP (green fluorescent protein).
Primary cortical neuron

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.