Wouters, Fred S., Prof. Dr.
Professor, Laboratory for Molecular and Cellular Systems
- Dr. (Ph.D.) 1997, Faculty of Chemistry, University of Utrecht, The Netherlands
- 1997 - 2000: Postdoctoral fellow, Imperial Cancer Research Fund (ICRF), London UK
- 2000 - 2001: Postdoctoral fellow, European Molecular Biology Laboratory (EMBL), Heidelberg
- 2001: Appointed as group leader at the European Neuroscience Institute, Göttingen
- PD (habilitation) 2006, Physiology, Göttingen University
- since July 2007 Professor
Major Research Interests
The focus of our research is the regulation and role of the neuronal cytoskeleton in the modulation of neuronal shape and motility during chemotactic processes. The growing neuronal growth cone probes its environment for the chemical composition of its substrate and the presence of neighbouring cells. The former information is sampled by cell adhesion receptors in focal adhesion structures that, next to their sensing function also perform a structural function in that they provide the cell with a means to exert force on its substrate. We are primarily interested in the signal transduction processes that regulate these effects and the cross-talk between the different motility systems.
The main interest areas in this question are; 1. The role and molecular mechanism of lipid raft-resident cell adhesion molecules in the remodelling of the membrane cytoskeleton, 2. Dynamic control of growth cone protein content by local proteolysis and chaperone function during chemotactic responses, 3. Role and mechanism of the neuronal exocyst complex as critical landmarks for dendritic/axonal neuritogenesis.
Our group has a related interest in the pathophysiological mechanism of neurodegeneration by intracellular aggregation of the tau protein, as occurs in Alzheimer's disease. As tau is an intrinsically unstructured protein that can undergo remarkable conformational changes upon binding to microtubules and in the Alzheimer-related aggregation condition, it presents an ideal model system for the biophysical analysis of protein conformational change and protein interactions.
Our research depends on the development and application of advanced microscopy techniques, primarily; fluorescence lifetime imaging microscopy (FLIM), and Förster resonance energy transfer (FRET) microscopy, in combination with a range of GFP-based optical biosensors and novel bioconjugation approaches for organic dyes, and protein biochemical/molecular biological techniques to resolve and quantify biochemical reactions and conditions in living cells.
Homepage Department/Research Group
Selected Recent Publications
- Liman J, Ganesan S, Dohm CP, Krajewski S, Reed JC, Bähr M, Wouters FS & Kermer P (2005) Interaction of BAG1 and HSP70 mediates neuroprotectivity and increases chaperone activity. Mol. Cell. Biol. 25, 3715-3725.
- Esposito A, Gerritsen HC & Wouters FS (2005) Fluorescence lifetime heterogeneity resolution in the frequency domain by Lifetime Moments Analysis ( LiMA ). Biophysical Journal 89, 4286-4299.
- Ganesan S, Ameer-beg SM, Ng T, Vojnovic B & Wouters FS. A dark yellow fluorescent protein (YFP)-based Resonance Energy Accepting Chromoprotein (REACh) for efficient FRET with GFP. Proc. Natl. Acad. Sci. USA (2006) 130 (11), 4089-4094.
- Esposito A, Gerritsen, HC, Oggier T, Lustenberger F. & Wouters FS. Innovating lifetime microscopy: a compact and simple tool for the life sciences, screening and diagnostics. J. Biomed. Optics (2006) 11 (3), 34016.
- Iliev AI, Ganesan S, Bunt G, Wouters FS (2006) Removal of small pattern-breaking stretches in microtubule-binding repeats produces instantaneous tau aggregation and toxicity. J. Biol. Chem 281: 37195-37204
- Iliev A, Wouters FS (2007) Application of simple photobleaching microscopy techniques for the determination of the balance between anterograde and retrograde axonal transport. J. Neurosci. Methods 161:39-46
- Iliev AI, Djannatian JR, Nau R, Mitchell TJ, Wouters FS (2007) Cholestrol-dependent actin remodeling via RhoA and Rac1 activation by the Streptococcus pneumoniae toxin pneumolysin. Proc. Natl. Acad. Sci. USA 104: 2897-2902
- Esposito A, Dohm CP, Kermer P, Bahr M, Wouters FS (2007) alpha-Synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiol. Dis 26: 521-531
- Esposito A, Dohm CP, Bahr M, Wouters FS (2007) Unsupervised fluorescence lifetime imaging microscopy for high content and high throughput screening Mol. Cell. Proteomics 6,:1446-1454
- Hillebrand M, Verrier SE, Ohlenbusch A, Schafer A, Soling HD, Wouters FS, Gartner J (2007) Live cell FRET Microscopy: homo- and heterodimerization of two human peroxisomal ABC transporters, the adrenoleukodystrophy protein (ALDP, ABCD1) and PMP70 (ABCD3). J. Biol. Chem 282: 26997-27005
- Pommereit D, Wouters FS. An NGF-induced Exo70-TC10 complex locally antagonises Cdc42-mediated activation of N-WASP to modulate neurite outgrowth. J. Cell Sci. 120: 2694-2705
- Esposito A, Gerritsen HC, Wouters FS (2007) Optimizing frequency-domain fluorescence lifetime sensing for high-throughput applications: photon economy and acquisition speed. J. Opt. Soc. Am. A 24: 3261-3273
- Ganesan S, Rohde G, Eckermann K, Sroka K, Schaefer MKE, Dohm CP, Kermer P, Haase G, Wouters FS, Bähr M, Weishaupt JH. Mutant SOD detoxification mechanisms in intact single cells. Cell Death Diff. In press