Joost Schymkowitz & Frederic Rousseau
Protein misfolding and aggregation
VIB SWITCH Laboratory, Vrije Universiteit Brussel
PhD: University of Cambridge ‘01
Postdoc: EMBL, Heidelberg, Germany, '01-'03
VIB Group leaders since 2003
e-mail: joost.schymkowitz@switch.vib-vub.be or frederic.rousseau@switch.vib-vub.be
phone +32 (0)2 629 1425
address: Free University of Brussels (VUB), Pleinlaan 2, 1050 Brussels, BELGIUM
Current team members
Group leaders: Joost Schymkowitz, Frederic Rousseau
Postdoctoral scientists: Kerensa Broersen, Stanislav Rudyak, Ashok Ganesan, Jan Griesbach, Jose Couceiro, Joost Van Durme, Javier Delgado
Ph.D. Students: Jie Xu, Annelies Vandersteen, Ola Siekierska, Jacinte Beerten, Rodrigo Gallardo, Lies Baeten, Peter Vanhee
Support personnel: Hannah Wilkinson, Maja Debulpaep, Wim Jonckheere, Ingrid Put
Science, relevant to NERF
Aging results in a decreased resistance of cells to physiological stress due to a gradual reduction of both proteasomal activity and inducible stress-response by chaperones. As a result, aged cells have an increased susceptibility for protein aggregation leading to loss-of-function of the affected protein. Moreover, aggregates of several proteins acquire a gain-of-toxic function by the formation of amyloid-like aggregates, causing ‘misfolding’ or ‘amyloid’ diseases. Aging neurons are particularly susceptible to protein aggregation resulting in illnesses such as Alzheimer disease, Parkinson disease, Huntington disease or amyotrophic lateral sclerosis to name only a few. Our group is interested in understanding the structural mechanisms of protein aggregation and how this affects neuronal activity. In particular, we are interested in understanding the ability of amyloid aggregates to interact with synaptic membranes and vesicles thereby inducing synaptotoxicity. Our research approach entails an integrated, multidisciplinary approach combining the use and development of bioinformatic algorithms to predict protein aggregation & chaperone interaction; in vitro biophysical studies of aggregation processes using techniques such as light scattering, Fourier-transform infrared microscopy or fluorescence anisotropy; cellular and physiological studies of aggregate toxicity and behavioral studies in mice.
Potential interactions with NERF
Using our multidisciplinary platform, we can offer tools to study the protein conformational processes leading to synaptic and neuronal disfunction and ultimately to neurodegeneration. In return, NERF might provide us the ability to study the effects of protein conformational processes on the activity of neuronal networks in much greater detail.
Selected publications
- Van Durme et al. Accurate prediction of DnaK-peptide binding via homology modelling and experimental data. PLoS Comput Biol (2009) vol. 5 (8) pp. e1000475
- Martins et al. Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice. EMBO J (2008) vol. 27 (1) pp. 224-33
- Fernandez-Escamilla et al. Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nat Biotechnol (2004) vol. 22 (10) pp. 1302-6
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