Prof. Dr. Ina Vorberg

Group Leader

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

ina.vorberg(at)dzne.de
+49 (0) 228 / 43302-560
+49 (0) 228 / 43302-685 (Secretary)

Group members

Name Phone
Carmen Rudert, Assistant +49 (0)228/43302-685
Dr. Shu Liu, Postdoc +49 (0)228/43302-578
Dr. Alexander Zielinski, Postdoc +49 (0)228/43302-541
Dr. Hanna Wolf, PostDoc +49 (0)228/43302-578
Yvonne Dürnberger, Ph.D. Student +49 (0)228/43302-578
Katrin Riemschoß, Ph.D. Student +49 (0)228/43302-576
Catharina Pleschka, Ph.D. Student +49 (0)228/43302-541
Lydia Paulsen, Technical Assistant +49 (0)228/43302-578
André Hossinger, Technical Assistant +49 (0)228/43302-578
Click on the magnifying glass for a large image.

Publications

Life cycle of cytosolic prions.

Hofmann J, Vorberg I. Prion. 2013 Sep 10;7(5). [Epub ahead of print]

Cell-to-cell propagation of infectious cytosolic protein aggregates.

Hofmann JP, Denner P, Nussbaum-Krammer C, Kuhn PH, Suhre MH, Scheibel T, Lichtenthaler SF, Schätzl HM, Bano D, Vorberg IM. Proc Natl Acad Sci USA.;2013 Apr 9;110(15):5951-6. doi: 10.1073/pnas.1217321110. Epub 2013 Mar 18.

Cellular aspects of prion replication in vitro.

Grassmann A, Wolf H, Hofmann J, Graham J, Vorberg I. Viruses. 2013 Jan 22;5(1):374-405. doi: 10.3390/v5010374.

Creutzfeldt-Jakob disease and mad cows: lessons learnt from yeast cells.

Hofmann J, Wolf H, Grassmann A, Arndt V, Graham J, Vorberg I. Swiss Med Wkly. 2012 Jan 24;142:0. doi: 10.4414/smw.2012.13505.

Effect of hydrophobic mutations in the H2-H3 subdomain of prion protein on stability and conversion in vitro and in vivo

I Hafner-Bratkovic, L Gaedtke, A Ondracka, P Veranic, I Vorberg, R Jerala; PLoS One. 2011;6(9):e24238. Epub 2011 Sep 1.

Proteasomal Dysfunction and Endoplasmic Reticulum Stress Enhance Trafficking of Prion Protein Aggregates through the Secretory Pathway and Increase Accumulation of Pathologic Prion Protein.

M Nunziante, K Ackermann, K Dietrich, H Wolf, L Gädtke, S Gilch, I Vorberg, M Groschup, HM Schätzl; J Biol Chem. 2011 Sep 30;286(39):33942-53. Epub 2011 Aug 11.

Globular domain of the prion protein needs to be unlocked by domain swapping to support prion protein conversion.

I Hafner-Bratkovic, R Bester, P Pristovsek, L Gaedtke, P Veranic, J Gaspersic, M Mancek-Keber, M Avbelj, M Polymenidou, C Julius, A Aguzzi, I Vorberg, R Jerala;
J Biol Chem. 2011 Feb 15. [Epub ahead of print]

Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR.

Roffe, M., Beraldo, F.H., Bester, R., Nunziante, M., Bach, C., Mancini, G., Gilch, S., Vorberg, I., Castilho, B.A., Martin, V.R., Hajj, G.N. (2010), Proc Natl Acad Sci 107, 13147-13152.

Tetracysteine-tagged PrP allows discrimination between the native PrPC and converted PrPSc forms.

Gaspersic, J., Hafner-Bratkovic, I., Stephan, M., Veranic, P., Bencina, M., Vorberg, I. and Jerala, R. (2010), FEBS J 277, 2038-2050.

Prion-like propagation of cytosolic protein aggregates- insights from cell culture models.

Krammer, C., Schätzl, H., Vorberg, I. (2009), Prion 4, 206-212.

Therapy in prion diseases: From molecular to cellular biology to therapeutic targets.

Krammer, C., Vorberg, I., Schätzl, H. and Gilch, S. (2009), Infect. Dis. - Drug Targets 9, 3-14.

Inhibition of cholesterol recycling impairs PrPSc propagation.

Gilch, S., Bach, C., Lutzny, G., Vorberg, I. and Schätzl, H.M. (2009), Cellular Molecular Life Sci. 66, 3979-3991.

Prion-induced activation of Srebp2-regulated gene expression in neuronal cells.

Bach, C., Gilch, S., Greenwood, A., Horsch, M., Facius, A., Schädler, S., Beckers, J., Leib-Mösch, C., Schätzl, H.*, Vorberg, I.* (2009), J. Biol. Chem. 284, 31260-31269.* Corresponding authors.

Dynamic interactions of Sup35 and PrP prion protein domains modulate aggregate nucleation and seeding.

Krammer, C., Kremmer, E., Schätzl, H.M. and Vorberg, I. (2008), Prion 2, 99-106 (Titelabbildung).

From the cover: The Sup35NM domain propagates as a prion in mammalian cells.

Krammer, C., Kryndushkin, D., Suhre, M.H., Kremmer, E., Hofmann, A., Pfeifer, A., Scheibel, T., Wickner, R., Schätzl, H.M. and Vorberg, I. (2009), Proc Natl Acad Sci 106, 462-467.

Acute cellular uptake of abnormal prion protein is cell type and scrapie strain independent.

Greil, C., Vorberg, I., Ward, A.E., Meade-White, K., Harris, D., Priola, S.A. (2008), Virology 379, 284-293.

Stress inducible phosphoprotein 1 (STI1) binding to the cellular prion protein (PrPC) in living cells triggers PrPC endocytosis and modulates cellular signaling.

Caetano, F.A., Lopes, M.H., Hajj, G., Machado, C.F., Magalhaes, A., De Paoli B. Vieira, M., Americo, T., Massensini, A.R., Priola, S.A., Vorberg, I., Linden, R., Prado, V.F., Martins, V.R., Prado, M.A.M. (2008), J Neurosci. 28, 6691-6702.

The novel sorting nexin SNX33 interferes with cellular prion infection by modulation of PrPC shedding.

Heiseke, A., Schöbel, S., Lichtenthaler, S.F., Vorberg, I., Kretzschmar, H., Schätzl, H., Nunziante, M. (2008), Traffic 9, 1116-1129.

Prion protein/protein interactions: fusion with the yeast Sup35p NM prion domain modulates cytosolic PrP aggregation in mammalian cells.

Krammer, C., Suhre, M., Kremmer, E., Diemer, C., Hess, S., Schätzl, H., Scheibel, T., Vorberg, I. (2008), FASEB J. 23, 762-773.

Scrapie infection of prion protein deficient cell line upon ectopic expression of mutant prion proteins.

Maas, E., Geissen, M., Groschup, M.H., Rost, R., Onodera, T., Schätzl, H., Vorberg, I. (2007), J Biol Chem. 282, 18702-18710.

Prion infection influences murine endogenous retrovirus expression in neuronal cells.

Stengel A., Bach C., Vorberg I., Frank O., Gilch S., Lutzny G., Seifarth W., Erfle V., Maas E., Schätzl H., Leib-Mösch C., Greenwood A.D. (2006), Biochem Biophys Res Commun. 343, 825-831.

DNA aptamers that bind to PrP(C) and not PrP(Sc) show sequence and structure specificity.

Takemura K., Wang P., Vorberg I., Surewicz W., Priola S.A., Kanthasamy A., Pottathil R., Chen S.G., Sreevatsan S. (2006), Exp Biol Med 231, 204-214.

Molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies.

Priola, S.A. and I. Vorberg (2006), Mol Biotechnol. 33, 71-88.

Cell line dependent RNA expression profiles of prion-infected mouse neuronal cells.

Greenwood A.D., Horsch M., Stengel A., Vorberg I., Lutzny G., Maas E., Schädler S., Erfle V., Beckers J., Schätzl H., Leib-Mösch C. (2005), J Mol Biol. 349, 487-500.

Species barriers in prion diseases-brief review.

Moore, R., Vorberg, I., Priola, S.A. (2005), Arch. Virol Suppl. 19, 187-202.

Molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies.

Priola, S.A., Vorberg, I. (2004), Methods Mol Biol 268, 517-540.

Identification of possible animal origins of prion disease in human beings.

Priola, S.A. and I. Vorberg (2004), Lancet 363, 2013-2014.

Acute formation of protease-resistant prion protein does not always lead to persistent scrapie infection in vitro.

Vorberg I., Raines A., Priola S.A. (2004), J Biol Chem. 279, 29218-29225.

Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents.

Vorberg I.*, Raines A., Story B., Priola S.A. (2004), J Infect Dis. 189, 431-439. * Corresponding Author.

Multiple amino acid residues within the rabbit prion protein inhibit formation of its abnormal isoform.

Vorberg I., Groschup M.H., Pfaff E., Priola S.A. (2003), J Virol. 77, 2003-2009.

Molecular basis of scrapie strain glycoform variation.

Vorberg I. and S.A. Priola (2002), J Biol Chem. 277, 36775-36781.

Deletion of beta-strand and alpha-helix secondary structure in normal prion protein inhibits formation of its protease-resistant isoform.

Vorberg I., Chan, C. Priola, S.A. (2001), J Virol. 75, 10024-10032.

The use of monoclonal antibody epitopes for tagging PrP in conversion experiments.

Vorberg I., Pfaff E. and Groschup M.H. (2000), Arch Virol Suppl. 16, 285-290.

A novel epitope for the specific detection of exogenous prion proteins in transgenic mice and transfected murine cell lines.

Vorberg I., Buschmann A., Harmeyer S., Saalmuller A., Pfaff E. and Groschup M.H. (1999), Virology 255, 26-31.

Curriculum Vitae


Areas of investigation/research focus

Research focus: Prion cell biology
Intra- and extracellular protein deposists are a hallmark of several so-called amyloid diseases including transmissible spongiform encephalopathies (TSEs, prion diseases), Alzheimer’s disease, Parkinson’s disease and tauopathies. TSEs are fatal neurodegenerative diseases of mammals that are associated with the misfolding of a host encoded protein, termed PrPC, into an aggregated isoform PrPSc.

Aggregation of disease-associated proteins apears to proceed via nucleated polymerization, whereby a seed of misfolded proteins acts as a template that drives the conformational transition of native homotypic proteins into misfolded isoforms. The view that prions are the only infectious amyloids has been challenged recently by several studies showing that other disease-related protein aggregates share at least some prion-like characteristics such as progressive non cell-autonomous induction within specific organs.

Our main interest is to elucidate differences and commonalities between prions and other amyloidogenic proteins and to dissect cellular pathways necessary for prion replication.

Nucleated polymerization model of amyloid formation. Prions are characterized by efficient fragmentation of growing aggregates into smaller transmissible propagons.
Nucleated polymerization model of amyloid formation. Prions are characterized by efficient fragmentation of growing aggregates into smaller transmissible propagons.Click on the magnifying glass for a large image.

Primary astrocytes. Blue: DAPI staining; Green: GFAP; Red: cellular PrP (PrPC). (A. Grassmann)
Primary astrocytes. Blue: DAPI staining; Green: GFAP; Red: cellular PrP (PrPC). (A. Grassmann)Click on the magnifying glass for a large image.

Research focus: Cellular replication mechanisms of TSE strains
Prion strain replication in vivo is associated with distinct pathophysiologies and with specific biochemical properties of PrPSc. In vitro cell lines differ remarkably in their relative susceptibility to specific TSE strains. The precise mechanism of how prions invade cells and in which cellular compartment they replicate is not well understood. The cellular isoform PrPC is a glycosylated protein anchored to the cell surface by a GPI moijety. Conversion into the abnormal isoform occurs after PrPC has reached the cell surface likely within an endocytic vesicle.

Our current research focuses on identifying factors modulating susceptibility of cells to specific prions and to elucidate if differences exist between the replication mechanisms of prion strains.

N2a neuroblastoma cell harboring Sup35p NM aggregates. Blue: DAPI staining; Red Phalloidin-Actin; Green: NM-GFP. (J. Hofmann)
N2a neuroblastoma cell harboring Sup35p NM aggregates. Blue: DAPI staining; Red Phalloidin-Actin; Green: NM-GFP. (J. Hofmann)Click on the magnifying glass for a large image.

Research focus: Prion-like replication of cytosolic protein aggregates
We are studying prion-like propagation of cytosolic protein aggregates in neuroblastoma cells and primary cells expressing the prion domain of the yeast protein Sup35p. We could previously show that the Sup35p domain NM exhibits prion characteristics also in mammalian cells. In our ongoing research we are focusing on intercellular spread of prion aggregates and inheritance of morphologically and biochemically distinct prion variants.

We hope to identify druggable targets for inhibition of non-cell autonomous protein aggregate induction and transmission.