Dr. Sybille Krauß
German Center for Neurodegenerative Diseases (DZNE)
Biomedical Center (BMZ1) - Building 344
+49 (0) 228 / 287-51113 (Büro)
+49 (0) 228 / 287-52129 (Labor)
+49 (0) 228 / 287-51625 (Secretary)
|Nancy El Deiry, Assistant||+49 (0)228 / 287-51625|
|Laura Jakobi, Trainee||+49 (0)228 / 287-52129|
|Judith Schilling, Ph.D. Student||+49 (0)228 / 287-52112|
|Dr. Nadine Griesche, Postdoc||+49 (0)228 / 287-52112|
|Dr. Frank Matthes, Postdoc||+49 (0)228 / 287-52112|
|Rohit Nalavade, Ph.D. Student||+49 (0)228 / 287-51703|
|Stephanie Dorn, Technical Assistant||+49 (0) 228 / 287-51703|
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.
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.
Areas of investigation/research focus
CAG trinucleotide repeats are found in a variety of genes and code for polyglutamine stretches in the respective proteins. The so-called polyglutamine diseases are characterized by expansion of CAG trinucleotide repeats, leading to expanded polyglutamine stretches in the disease causing proteins. To date, nine polyglutamine diseases are known. The most common polyglutamine disease is Huntington’s Chorea (HD) with a prevalence of 1:10.000 individuals. HD is caused by an abnormal CAG repeat expansion in the coding region of the Huntingtin gene. The phenotype of HD is characterized by progressive neuronal cell death associated with mood swings, choreic movements and progressive dementia. Another polyglutamine disease, spinocerebellar ataxia type 3 (SCA3), is caused by a CAG repeat expansion in the ATXN3 gene and represents the most common dominantly inherited ataxia. Symptoms of SCA3 include gait ataxia, spasticity, difficulty with speech and swallowing, weakness in arms and legs, clumsiness, and involuntary eye movements.
A pathological hallmark of several polyglutamine diseases is the aggregation of polyglutamine-expanded proteins. Although many cellular processes like atypical assembly of polyglutamine proteins, aggregate formation, protein degradation, transcriptional dysregulation, or mitochondrial processes have been associated with the disease pathogenesis, the mechanisms underlying the selective neurotoxicity in polyglutamine diseases remain obscure.
The aim of our studies is to investigate regulatory RNA-protein interactions that control the production of polyglutamine proteins. We have identified a protein complex, which binds to and regulates the translation of mRNAs containing CAG repeats. One of our research projects focuses on the detailed characterization of this protein complex and its impact on the synthesis of protein from mRNA with expanded CAG repeats.
In a second project we investigate the role of microRNAs (miRNA) in polyglutamine diseases. miRNAs are small noncoding RNAs, which bind to the 3’UTR of their target mRNAs and thereby suppress protein production.
In another research project, we are studying the role of a protein complex, which regulates protein phosphatase 2A (PP2A) activity. Hyperphosphorylated tau plays an important role in the formation of neurofibrillary tangles in brains of patients with Alzheimer’s disease (AD) and related tauopathies and is a crucial factor in the pathogenesis of these disorders. A reduced expression and/or activity of PP2A was shown to be involved in neurodegenerative disorders like AD. Therefore, induction of PP2A activity might be beneficial in such a context. The aim of this project is to identify ways to manipulate this inhibitory PP2A-complex and thereby induce phosphatase activity.
For our investigations we are using a broad panel of biochemical, molecular and cell biological methods.