Frederic Rousseau & Joost Schymkowitz
VIB Switch Laboratory, Vrije Universiteit Brussel

Frederic Rousseau PhD: Univ. of Cambridge, Cambridge, UK, '01 Postdoc: EMBL, Heidelberg, Germany, '01-'03 VIB Group leader since 2003 Joost Schymkowitz PhD: Univ. of Cambridge, Cambridge, UK, '01 Postdoc: EMBL, Heidelberg, Germany, '01-'03 VIB Group leader since 2003

e-mail phone +32 2 629 14 25 ADDRESS e-mail phone +32 2 629 14 25 ADDRESS

Current team members
Group leaders: Frederic Rousseau, Joost Schymkowitz
Postdoctoral scientists: Alain Coletta, Ashok Ganesan, Frederik De Smet, Jan Griesbach, Javier Delgado Blanco, Joost Van Durme, José Couceiro, Kerensa Broersen, Stanislav Rudyak, Virginie De Schaetzen
Ph.D. Students: Annelies Vandersteen, Greet de Baets, Jacinte Beerten, Jie Xu, Ola Siekierska, Peter Vanhee, Rodrigo Gallardo
Support personnel: Hannah Wilkinson, Maja Debulpaep, Wim Jonckheere

Keywords
protein aggregation - protein stability - protein design - protein interaction - force field - Alzheimer beta-peptide

Science
The Switch Laboratory focuses on essential cellular processes where functional regulation is governed by protein conformational switches that have to be actively controlled to ensure cell viability. The lab employs a a multidisciplinary approach that combines in vitro biophysical techniques and computational structural biology methods with advanced cell biological studies. The research focusses on

1. protein (mis)folding, aggregation and amyloidosis: what is the relationship between the structure of protein aggregates and chaperone recognition?
2. protein dynamics and signal transduction: how do conformational fluctuations of the native state achieve signal transduction?
3. non-synonymous SNPs and the molecular phenotype of proteins: how does human genetic variability affect protein stability, folding and aggregation?

Algorithms – We have contributed to the development of several computational algorithms to predict  and simulate protein aggregation (TANGO) and amyloidosis (in progress) but also protein stability, dynamics and folding (FOLDX).

Protein Aggregation – Using TANGO, we were able to show that proteins are subject to strong evolutionary pressure against aggregation and that proteins possess specialized residues, termed gatekeepers, that are specifically selected to oppose protein aggregation and that chaperones evolved to recognize such gatekeeper residues. The precise interaction between chaperones and the gatekeeper motif is currently being investigated using both simulations and wet lab experimentation on chaperone specificity and peptide aggregation.

Signal Transduction – In the field of signal transduction, the FoldX algorithm is used to simulate protein dynamics and to determine communication channels for signal transduction between distal sites in globular proteins, using a framework borrowed from noisy channel theory.

SNPeffect – Single nucleotide polymorphisms constitute the most fundamental type of genetic variation in human populations. An important goal in genomic research is to understand how this variability affects protein function, and whether or not particular SNPs are associated to disease susceptibility. Accordingly, the SNPeffect database uses sequence and structure-based bioinformatics tools to predict the effect of non-synonymous SNPs on the molecular phenotype of proteins.

Go to Switch's own website for more details.

Press Release
See also press release (10/12/2007): Lipids in the brain an important factor for Alzheimer's disease? Flemish scientists crack the code - based on a publication in The EMBO Journal (Martins et al., The EMBO Journal, 2007)

Maurer-Stroh S, Debulpaep M, Kuemmerer N, De La Paz M, Martins I, Reumers J, Morris K, Copland A, Serpell L, Serrano L, Schymkowitz J, Rousseau F
Exploring the sequence determinants of amyloid structure using position-specific scoring matrices
NAT METHODS 7, 237-42, 2010



Vanhee P, Stricher F, Baeten L, Verschueren E, Lenaerts T, Serrano L, Rousseau F, Schymkowitz J
Protein-peptide interactions adopt the same structural motifs as monomeric protein folds
STRUCTURE 17, 1128-36, 2009



Martins I, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M, Jonckheere W, Van Gelder P, Hartmann D, D'hooge R, De Strooper B, Schymkowitz J, Rousseau F
Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice
EMBO J 27, 224-33, 2008



Rousseau F, Serrano L, Schymkowitz J
How evolutionary pressure against protein aggregation shaped chaperone specificity
J MOL BIOL 355, 1037-47, 2006



Fernandez-Escamilla m, Rousseau F, Schymkowitz J, Serrano L
Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins
NAT BIOTECHNOL 22, 1302-1306, 2004

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