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MANGO SIGNED

The determinants of cross-seeding of protein aggregation: a Multiple TANGO

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Project "MANGO" data sheet

The following table provides information about the project.

Coordinator
VIB 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Total cost 1˙995˙523 €
 EC max contribution 1˙995˙523 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB BE (ZWIJNAARDE - GENT) coordinator 1˙995˙523.00

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 Project objective

Amyloid-like protein aggregation is a process of protein assembly via the formation of intermolecular β-structures by short aggregation prone sequence regions. This occurs as an unwanted side-reaction of impaired protein folding in disease, but also for the construction of natural nanomaterials. Aggregates appear to be strongly enriched in particular proteins, suggesting that the assembly process itself is specific, but the cross-seeding of the aggregation of one protein by aggregates of another protein has also been reported.

The key question that I aim to address in this proposal is how the beta-interactions of the amino acids in the aggregate spine determine the trade-off between the specificity of aggregation versus cross-seeding. To this end, I will determine the energy difference between homotypic versus heterotypic interactions and how differences in sequence translate into energy gaps. Moreover, I will analyse the sequence variations of aggregation prone stretches in natural proteomes to understand the danger of widespread co-aggregation.

To achieve these outcomes, I will study the interactions and cross-seeding of aggregating proteins and model peptides in vitro and in cells. I will extract the sequence and structural determinants of co-aggregation, and employ these to construct novel bioinformatics algorithm that can accurately predict co-aggregation and cross-seeding. I will use these to analyse co-aggregation cascades in natural proteomes looking for mechanisms that protect them from wide-spread cross-seeding.

This work will have a significant impact on the understanding of the downstream effects of protein aggregates and may reveal co-aggregation networks in human diseases such as the major neurodegenerative diseases or cancer, potentially opening up new research lines on the mechanisms underlying these pathologies and thus identify targets for novel therapies.

 Publications

year authors and title journal last update
List of publications.
2017 Khodaparast, Laleh
The Possible Role of the Staphylococcus epidermidis LPxTG Surface Protein SesC in Biofilm Formation and its use as a potential vaccine target : DE MOGELIJKE ROL VAN DE STAPHYLOCOCCUS EPIDERMIDIS LPXTG OPPERVLAKTE-EIWIT SESC IN BIOFILMVORMING EN HET GEBRUIK ERVAN ALS EEN POTENTIEEL VACCIN DOELWIT
published pages: , ISSN: , DOI:
1 2020-02-04
2018 Elsa Lauwers, Yu-Chun Wang, Rodrigo Gallardo, Rob Van der Kant, Emiel Michiels, Jef Swerts, Pieter Baatsen, Samantha S. Zaiter, Shelli R. McAlpine, Natalia V. Gounko, Frederic Rousseau, Joost Schymkowitz, Patrik Verstreken
Hsp90 Mediates Membrane Deformation and Exosome Release
published pages: 689-702.e9, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.07.016
Molecular Cell 71/5 2020-02-04
2018 Konstantinos C. Tsolis, Evridiki-Pandora Tsare, Georgia Orfanoudaki, Tobias Busche, Katerina Kanaki, Reshmi Ramakrishnan, Frederic Rousseau, Joost Schymkowitz, Christian Rückert, Jörn Kalinowski, Jozef Anné, Spyridoula Karamanou, Maria I. Klapa, Anastassios Economou
Comprehensive subcellular topologies of polypeptides in Streptomyces
published pages: , ISSN: 1475-2859, DOI: 10.1186/s12934-018-0892-0
Microbial Cell Factories 17/1 2020-02-04
2017 Khodaparast, Ladan
PROTEIN AGGREGATION AS A NEW STRATEGY TO COMBAT GRAM NEGATIVE BACTERIA : PROTEÏNEAGGREGATIE ALS EEN NIEUWE STRATEGIE OM BACTERIËN TE BESTRIJDEN
published pages: , ISSN: , DOI:
2 2020-02-04
2018 Steven Boeynaems, Simon Alberti, Nicolas L. Fawzi, Tanja Mittag, Magdalini Polymenidou, Frederic Rousseau, Joost Schymkowitz, James Shorter, Benjamin Wolozin, Ludo Van Den Bosch, Peter Tompa, Monika Fuxreiter
Protein Phase Separation: A New Phase in Cell Biology
published pages: 420-435, ISSN: 0962-8924, DOI: 10.1016/j.tcb.2018.02.004
Trends in Cell Biology 28/6 2020-02-04
2015 Greet De Baets, Loic Van Doorn, Frederic Rousseau, Joost Schymkowitz
Increased Aggregation Is More Frequently Associated to Human Disease-Associated Mutations Than to Neutral Polymorphisms
published pages: e1004374, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1004374
PLOS Computational Biology 11/9 2020-02-04
2017 Saiz Rubio, Mirian
Aggregation as a mechanism for p53 oncogenic transformation: clinical relevance and new tools for its study : Aggregatie als een mechanisme voor p53-gemedieerde oncogene transformatie: klinische relevantie en nieuwe manieren om dit te bestuderen.
published pages: , ISSN: , DOI:
1 2020-02-04
2016 Ana Zafra Ruano, Elisa Cilia, José R. Couceiro, Javier Ruiz Sanz, Joost Schymkowitz, Frederic Rousseau, Irene Luque, Tom Lenaerts
From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors
published pages: e1004938, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1004938
PLOS Computational Biology 12/5 2020-02-04
2018 Elke Bogaert, Steven Boeynaems, Masato Kato, Lin Guo, Thomas R. Caulfield, Jolien Steyaert, Wendy Scheveneels, Nathalie Wilmans, Wanda Haeck, Nicole Hersmus, Joost Schymkowitz, Frederic Rousseau, James Shorter, Patrick Callaerts, Wim Robberecht, Philip Van Damme, Ludo Van Den Bosch
Molecular Dissection of FUS Points at Synergistic Effect of Low-Complexity Domains in Toxicity
published pages: 529-537.e4, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.06.070
Cell Reports 24/3 2020-02-04
2018 Ladan Khodaparast, Laleh Khodaparast, Rodrigo Gallardo, Nikolaos N. Louros, Emiel Michiels, Reshmi Ramakrishnan, Meine Ramakers, Filip Claes, Lydia Young, Mohammad Shahrooei, Hannah Wilkinson, Matyas Desager, Wubishet Mengistu Tadesse, K. Peter R. Nilsson, Per Hammarström, Abram Aertsen, Sebastien Carpentier, Johan Van Eldere, Frederic Rousseau, Joost Schymkowitz
Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03131-0
Nature Communications 9/1 2020-02-04
2017 Steven Boeynaems, Elke Bogaert, Denes Kovacs, Albert Konijnenberg, Evy Timmerman, Alex Volkov, Mainak Guharoy, Mathias De Decker, Tom Jaspers, Veronica H. Ryan, Abigail M. Janke, Pieter Baatsen, Thomas Vercruysse, Regina-Maria Kolaitis, Dirk Daelemans, J. Paul Taylor, Nancy Kedersha, Paul Anderson, Francis Impens, Frank Sobott, Joost Schymkowitz, Frederic Rousseau, Nicolas L. Fawzi, Wim Robberecht, Philip Van Damme, Peter Tompa, Ludo Van Den Bosch
Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics
published pages: 1044-1055.e5, ISSN: 1097-2765, DOI: 10.1016/J.MOLCEL.2017.02.013
Molecular Cell 65/6 2019-06-06
2017 Rob van der Kant, Anne R. Karow-Zwick, Joost Van Durme, Michaela Blech, Rodrigo Gallardo, Daniel Seeliger, Kerstin Aßfalg, Pieter Baatsen, Griet Compernolle, Ann Gils, Joey M. Studts, Patrick Schulz, Patrick Garidel, Joost Schymkowitz, Frederic Rousseau
Prediction and Reduction of the Aggregation of Monoclonal Antibodies
published pages: 1244-1261, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2017.03.014
Journal of Molecular Biology 429/8 2019-06-06
2016 Antonio Luis Egea-Jimenez, Rodrigo Gallardo, Abel Garcia-Pino, Ylva Ivarsson, Anna Maria Wawrzyniak, Rudra Kashyap, Remy Loris, Joost Schymkowitz, Frederic Rousseau, Pascale Zimmermann
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
published pages: 12101, ISSN: 2041-1723, DOI: 10.1038/ncomms12101
Nature Communications 7 2019-06-06
2016 Ashok Ganesan, Aleksandra Siekierska, Jacinte Beerten, Marijke Brams, Joost Van Durme, Greet De Baets, Rob Van der Kant, Rodrigo Gallardo, Meine Ramakers, Tobias Langenberg, Hannah Wilkinson, Frederik De Smet, Chris Ulens, Frederic Rousseau, Joost Schymkowitz
Structural hot spots for the solubility of globular proteins
published pages: 10816, ISSN: 2041-1723, DOI: 10.1038/ncomms10816
Nature Communications 7 2019-06-06
2017 Tobias Langenberg, Joost Schymkowitz, Frederic Rousseau
Identifying rescuers of misfolding
published pages: 782-783, ISSN: 2157-846X, DOI: 10.1038/s41551-017-0149-y
Nature Biomedical Engineering 1/10 2019-06-06
2017 Frederik De Smet, Mirian Saiz Rubio, Daphne Hompes, Evelyne Naus, Greet De Baets, Tobias Langenberg, Mark S Hipp, Bert Houben, Filip Claes, Sarah Charbonneau, Javier Delgado Blanco, Stephane Plaisance, Shakti Ramkissoon, Lori Ramkissoon, Colinda Simons, Piet van den Brandt, Matty Weijenberg, Manon Van England, Sandrina Lambrechts, Frederic Amant, André D\'Hoore, Keith L Ligon, Xavier Sagaert, Joost Schymkowitz, Frederic Rousseau
Nuclear inclusion bodies of mutant and wild-type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation
published pages: 24-38, ISSN: 0022-3417, DOI: 10.1002/path.4872
The Journal of Pathology 242/1 2019-06-06
2017 Camilla Betti, Joost Schymkowitz, Frederic Rousseau, Eugenia Russinova
Selective Knockdowns in Maize by Sequence-Specific Protein Aggregation
published pages: 109-127, ISSN: , DOI: 10.1007/978-1-4939-7315-6_6
Methods in Molecular Biology 2019-06-06
2016 Camilla Betti, Isabelle Vanhoutte, Silvie Coutuer, Riet Maria De Rycke, Kiril Mishev, Marnik Vuylsteke, Stijn Aesaert, Debbie Rombaut, Rodrigo Gallardo, Frederik De Smet, Jie Xu, Mieke Van Lijsebettens, Frank Van Breusegem, Dirk Inzé, Frederic Rousseau, Joost Schymkowitz, Eugenia Russinova
Sequence-specific protein aggregation generates defined protein knockdowns in plants
published pages: pp.00335.2016, ISSN: 0032-0889, DOI: 10.1104/pp.16.00335
Plant Physiology 2019-06-06
2016 Joost Van Durme, Greet De Baets, Rob Van Der Kant, Meine Ramakers, Ashok Ganesan, Hannah Wilkinson, Rodrigo Gallardo, Frederic Rousseau, Joost Schymkowitz
Solubis: a webserver to reduce protein aggregation through mutation
published pages: 285-289, ISSN: 1741-0126, DOI: 10.1093/protein/gzw019
Protein Engineering Design and Selection 29/8 2019-06-06
2016 Joost Schymkowitz, Frederic Rousseau
A rescue by chaperones
published pages: 58-59, ISSN: 1552-4450, DOI: 10.1038/nchembio.2006
Nature Chemical Biology 12/2 2019-06-06
2016 Xiao-Jiang Quan, Liqun Yuan, Luca Tiberi, Annelies Claeys, Natalie De Geest, Jiekun Yan, Rob van der Kant, Wei R. Xie, Tiemo J. Klisch, Joost Shymkowitz, Frederic Rousseau, Mathieu Bollen, Monique Beullens, Huda Y. Zoghbi, Pierre Vanderhaeghen, Bassem A. Hassan
Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis
published pages: 460-475, ISSN: 0092-8674, DOI: 10.1016/j.cell.2015.12.048
Cell 164/3 2019-06-06
2016 Ragna Sannerud, Cary Esselens, Paulina Ejsmont, Rafael Mattera, Leila Rochin, Arun Kumar Tharkeshwar, Greet De Baets, Veerle De Wever, Roger Habets, Veerle Baert, Wendy Vermeire, Christine Michiels, Arjan J. Groot, Rosanne Wouters, Katleen Dillen, Katlijn Vints, Pieter Baatsen, Sebastian Munck, Rita Derua, Etienne Waelkens, Guriqbal S. Basi, Mark Mercken, Marc Vooijs, Mathieu Bollen, Joost Schymkowitz, Frederic Rousseau, Juan S. Bonifacino, Guillaume Van Niel, Bart De Strooper, Wim Annaert
Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aβ Pool
published pages: 193-208, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.05.020
Cell 166/1 2019-06-06
2016 Rodrigo Gallardo, Meine Ramakers, Frederik De Smet, Filip Claes, Ladan Khodaparast, Laleh Khodaparast, José R. Couceiro, Tobias Langenberg, Maxime Siemons, Sofie Nyström, Laurence J. Young, Romain F. Laine, Lydia Young, Enrico Radaelli, Iryna Benilova, Manoj Kumar, An Staes, Matyas Desager, Manu Beerens, Petra Vandervoort, Aernout Luttun, Kris Gevaert, Guy Bormans, Mieke Dewerchin, Johan Van Eldere, Peter Carmeliet, Greetje Vande Velde, Catherine Verfaillie, Clemens F. Kaminski, Bart De Strooper, Per Hammarström, K. Peter R. Nilsson, Louise Serpell, Joost Schymkowitz, Frederic Rousseau
De novo design of a biologically active amyloid
published pages: aah4949, ISSN: 0036-8075, DOI: 10.1126/science.aah4949
Science 354/6313 2019-06-06

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