BioSCENTer - BioMolecular Interaction (BioMint)

Contact person

Prof. Yves Engelborghs
Lab. Biomolecular Dynamics
Celestijnenlaan 200 G box 2403
B3001 Leuven
Tel: +32 16 32 71 60
fax: +32 16 32 79 72
Email: Yves.Engelborghs@fys.kuleuven.be

Prof. Jos Vanderleyden
Kasteelpark Arenberg
Kardinaal Mercierlaan
B3001 Leuven
Tel.:+32 16 32 96 79
Fax.: +32 16 32 19 66
Email: jozef.vanderleyden@biw.kuleuven.be

Prof. Joris Winderickx
Kasteelpark Arenberg
Kardinaal Mercierlaan
B3001 Leuven
Tel.:+32 16 32 15 16
Fax.: +32 16 32 19 67
Email.: Joris.Winderickx@bio.kuleuven.be

Partners

  • Faculty of Science
    • Department of Chemistry, section Biochemistry, Molecular and Structural Biology: M. De Ley, M. De Maeyer, Y. Engelborghs, C. Gielens, L. Van Meervelt, J. Robben.
    • Department of Chemistry, section Molecular and Nanomaterials; J. Hofkens, S. Defeyter
    • Department of Biology, section Molecular Physiology of Plants and Micro-organisms: W. Vanden Ende, J. Winderickx
    • Department of Biology, section Animal Physiology and Neurobiology; L. Arckens, V. Darras, R. Huybrechts, L. Moons, L. Schoofs, J. Vanden Broeck
    • Department of Biology, section Microbiology and Biotechnology; J. Thevelein, P. Van Dijck
    • Department of Physics, Section Biophysics, E. Carlon and J. Rogiers
    • Campus Kortrijk : Faculty of Sciences, Department of Chemistry, section Biochemistry, Laboratory for Thrombosis Research; H. Deckmyn, K. Vanhoorelbeke
  • Faculty of Bioscience Engineering
    • Department of Microbial and Molecular Systems (M²S), Centre of Microbial and Plant Genetics; W. Broekaert, B. Cammue, R. De Mot, K. Marchal, J. Michiels, J. Vanderleyden, K. Verstrepen

Background and goal

Living organisms are characterized by the coordinated and dynamic regulation of metabolic and regulatory processes that control their development, growth and adaptation to environmental stimuli. Recent advances in molecular biology made it possible to study all the facets of these processes. The ultimate goal is to understand the function, regulation and interplay of biomolecules and to place series of well-defined single molecular events into a network of dynamic process interactions underlying the physiological properties of biological systems. The BioMint cluster covers the study of biomolecular interactions from single molecules to whole organisms. It involves the BIOMACS center which is focussed on the structure determination of biomolecules by crystallization or NMR spectrometry as well as on the modelling of molecules and their interactions, and the model-driven manipulation of structures. Other laboratories of the cluster are specialized in the study of molecular dynamics and interactions via a variety of fluorescence microscopy techniques e.g. single molecule spectroscopy, fluorescence correlation microscopy, FLIM, fluorescence anisotropy, in vitro and in the living cell. These laboratories host a wide variety of techniques for the quantification of molecular dynamics and affinities in low and high throughput mode. Yet other groups, including SymBioSys, study gene-protein and protein-protein interactions, either single case or genome- and proteome-wide, to describe cellular signalling events allowing for dynamic adaptations of biological systems. A focus on the molecular build-up of signalling modules into signalling pathways, their feed-forward and feedback regulation and mechanisms for cross-talk between these pathways is complemented by a focus on the pathway-based functional biology of organism - stimulus interactions. The goal is to make the different techniques and expertise of the BioMint cluster available to all the partners in the BioSCENTer network for data generation and/or hypothesis validation.

Strategic mission

The mission of the BioMint cluster is to provide the expertise necessary for the study of biomolecular interactions, from single molecules to molecular ensembles in cells, tissues and organisms. It brings together experts in the modeling of biomolecular structure, function and dynamics, the determination of biomolecular structures and the quantification of biomolecular interactions in vitro and in living systems. The cluster participates heavily in the development of technology for increasing space- and time- resolved observation and for large scale and high throughput interaction studies.

Research lines

RL 1: Macromolecular structure/function/dynamics: modelling and determination. Responsible: Hans Deckmyn

  • Identification of determinants for self-assembly of natively unfolded proteins.
  • Atomic force microscopy of molecyular structures, DNA – protein complexes (HIV; recombination proteins) and DNA – dye complexes.
  •  
  • Molecular dynamics and molecular recognition via time resolved fluorescence spectroscopy and computer modelling
  • rational design and high throughput screening for small molecules mimicking the antithrombotic action of characterised antibodies
  • Structure-function analyses on invertases and glycosyl hydrolases to create superior enzymes to increase plant yield, stress resistence and optimize healthy food and feed ingredients

RL 2: Experimental studies for screening, quantification and validation of intermolecular interactions in the living cell Responsible:Yves Engelborghs

  • Dynamic studies of protein-protein and protein-nucleic acid interactions in the living cell
  • Dynamic studies of protein-protein interactions in the membranes of living cells
  • Developing test systems for drug targeting against protein-protein interactions
  • Specificity determinants of regulated protein degradation
  • Functional characterization of (neuro)peptides and their receptors
  • Functional genomic analysis of haemostatic and platelet proteins by silencing (siRNA, transposon) or tissue specific expression in vivo
  • development of different gene therapy approaches, with model system the bleeding disorder von Willebrand disease

RL 3: Integration of interaction information into biomolecular modules, pathways and networks Responsible: Joris Winderickx

  • Deciphering gene regulatory programs for quorum sensing in Salmonella
  • Identify sensing and signal transduction mechanisms for the dynamic control of stress and nutrient-responsive signalling networks in yeast
  • Identify molecular mechanisms for plasticity in the mammalian neocortex
  • Influencing sucrose metabolism and sugar signaling to increase plant biomass production and delay plant senescence
  • Molecular genetic and proteomic approaches to the study of protein complex composition, dynamics and regulation
  • Hormonal control of pre- and posttranslational mechanisms in protein expression;
  • Molecular properties and signal transduction pathways of G protein-coupled receptors;

RL4: Functional significance of biomolecular interactions in living organisms Responsible: Lut Arckens

  • Characterization of the molecular mechanisms of plasticity in the mammalian sensory neocortex;
  • Identify networks of hormone-structural protein interactions in the developing vertebrate brain;
  • Deciphering genetic/molecular interactions between proteinases and other signaling and guidance molecules, involved in neuronal and axonal patterning, using in vivo and ex vivo vertebrate animal models to study neural circuit development and regeneration;
  • Functional analysis of peptide-receptor interactions in a variety of small animal models
  • Unravelling neuro-endocrine mechanisms that control locust reproduction and fase transition;

RL 5: Technology development for increasing space- and time-resolved microscopy Responsible: Johan Hofkens

  • Photo-activation localization microscopy (PALM)
  • Stimulated emission depletion microscopy (STED)
  • Multiparametric single molecule microscopy (SMS)
  • Life-time imaging
  • Combination of AFM and optical microscopy
  • single molecule analysis of (i) conformational changes in von Willebrand Factor and (ii) regulation of the VWF cleaving protease ADAMTS13, both induced by shear forces

RL 6: Technology development for large scale/high throughput interaction studies (genomics, transciptomics, proteomics, metabolomics) Responsible: Jos Vanderleyden

  • Optimize Chip-chip analysis for signalling network inference
  • Optimize peptidomics methodologies for real time expression of the Drosophila peptidome
  • ...

RL 7: Data integration into molecular and cellular model systems Responsible: Kathleen Marchal (by nominating a PI that for the main research activity is located in another cluster, we aim to give a clear sign of the ambition to work towards strong integration. It also reflects positioning of SymBioSys within BioSCENTer)

  • Development of humanized yeast model systems for drug discovery and fundamental studies in neuropathology, apoptosis and cancer.
  • ...

Track record

Key publications

Van der Geyten, S., Segers, I., Gereben, B., Bartha, T., Rudas, P., Larsen, P.R., Kühn, E.R. & Darras, V.M. (2001). Transcriptional regulation of iodothyronine deiodinases during embryonic development. Molecular Cellular Endocrinology 183: 1-9. Marchal, K., Thijs, G., De Keersmaecker, S., Monsieurs, P., De Moor B., and Vanderleyden, J. (2003) Genome-specific higher-order background models to improve motif detection. Trends Microbiol. 11: 61-66

Hens K, Lemey P, Macours N, Francis C, Huybrechts R. (2004) Cyclorraphan yolk proteins and lepidopteran minor yolk proteins originate from two unrelated lipase families. Insect Mol Biol. 13:615-23.

Simonet, G., Poels, J., Claeys, I., Van Loy, T., Franssens, V., De Loof, A. & Vanden Broeck, J. (2004) Neuro-endocrinological and molecular aspects of insect reproduction. Journal of Neuroendocrinology 16: 649-659.

Van den Bergh G. and Arckens L. (2004) Fluorescent two-dimensional difference gel electrophoresis unveils the potential of gel-based proteomics. Current Opinion in Biotechnology 15: 38-43.

Van den Ende W., De Coninck, B., Van Laere, A. (2004). Plant fructan exohydrolases: a role in signaling and defense? TRENDS in Plant Science 9: 523-528.

Vierstraete E, Verleyen P, Baggerman G, D'Hertog W, Van den Bergh G, Arckens L, De Loof A, Schoofs L. (2004) A proteomic approach for the analysis of instantly released wound and immune proteins in Drosophila melanogaster hemolymph. Proc Natl Acad Sci U S A. 101:470-5.

Heymans S, Lupu F, Terclavers S, Vanwetswinkel B, Herbert JM, Baker A, Collen D, Carmeliet P, Moons L. (2005). Loss or inhibition of uPA or MMP-9 attenuates LV remodeling and dysfunction after acute pressure overload in mice. Am J Pathol. 166:15-25.

Noben JP, Dumont D, Kwasnikowska N, Verhaert P, Somers V, Hupperts R, Stinissen P, Robben J. (2006) Lumbar cerebrospinal fluid proteome in multiple sclerosis: characterization by ultrafiltration, liquid chromatography, and mass spectrometry. J Proteome Res. 5:1647-1657.

Roosen J., Engelen K., Marchal K., Mathys J., Griffioen G., Cameroni C., Thevelein J., De Virgilio C., De Moor B., and Winderickx J. (2005) PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability. Mol. Microbiol. 55: 862-880

Roeffaers M.B.J., Sels B.F., Uji-i H., De Schryver F.C., Jacobs P.A., De Vos D.E., Hofkens J. (2006) Spatially resolved observation of crystal-face-dependent catalysis by single turnover counting. Nature 439: 572-575

Staelens S, MA Hadders, S Vauterin, C Platteau, M De Maeyer, K Vanhoorelbeke, EG Huizinga, H Deckmyn. (2006) Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain. J Biol Chem 281:2225-2231

Margineanu A., De Feyter S., Melnikov S., Chaltin P., van Aerschot A., Herdewijn P., Habuchi S., De Schryver F. C., Hofkens J. (2007) Complexaton between lipofectamine and cholesterol-modified DNA sequences studied by single molecule fluorescence techniques. Biomacromolecules 8: 3382 - 3392

Tudor C, Feige JN, Pingali H, Lohray VB, Wahli W, Desvergne B, Engelborghs Y, Gelman L.(2007) Association with coregulators is the major determinant governing peroxisome proliferator-activated receptor mobility in living cells. J Biol Chem. 282:4417-26.

Weckx S, Carlon E., De Vuyst L., van Hummelen P. (2007) Thermodynamic Behavior of Short Oligonucleotides in Microarray Hybridizations Can Be Described Using Gibbs Free Energy in a Nearest-Neighbor Model. J. Phys. Chem. B 111: 13583

Fontayne A, De Maeyer B, De Maeyer M, Yamashita M, Matsushita T, Deckmyn H (2007) Paratope and epitope identification of the antithrombotic antibody 6B4 in complex with GPIbalpha. J Biol Chem 282:23517-24

Major projects

  • K.U.Leuven EF: SYMBIOSYS: K.U.Leuven Center for Computational Systems Biology (2005 – 2010)
  • K.U.Leuven of Excellence, Centre of Excellence in Catalysis (CECAT) (2006-2010)
  • Impulsfinanciering BioMacS: K.U.Leuven
  • K.U.Leuven GOA: Multidisciplinary approach to study Parkinson's Disease: from basic neurobiology to development and validation of novel model systems and therapeutic strategies. (2009-2013)
  • K.U.Leuven GOA: Genetic analysis, manipulation and correction of molecular pathways involved in blood platelet formation and function (2009-2013)
  • K.U.Leuven GOA: Unraveling the endocrinology of phase transition and reproduction in locusts. (2005-2009)
  • K.U.Leuven GOA: Probing dynamics in individual (bio)molecules with single molecule Spectroscopy (2006-2010)
  • K.U.Leuven CIF: Functional prioritization and experimental validation of genes expressed in human blood platelets (2007-2012)
  • IWT SBO Functional Peptidomics (2006-2009)
  • IWT SBO: Fluorescence Correlation Spectroscopy for evaluation and valorisation of drug-target interactions in the living cell (-2007)
  • IOF-KP: Opstellen van een "rational drug design" strategie voor identificatie van eiwit-bindende functionele kleine moleculen, door integratie van structuurgegevens met in silico en in vitro screening. (2006-2010)
  • IOF-KP: Technologieplatform voor validatie van nieuwe therapeutische doelwitten voor de ziekte van Parkinson en ontwikkeling van geneesmiddelen gericht tegen de gevalideerde doelwitten (KUL-PARK) (2008-2012)
  • EU-FP6: Marie Curie Research Training Network MRTN-CT-2004-512161 Chiral Expression and Transfer at the Nanoscale (2004 – 2008)
  • EU-FP7 Small Collaborative Project: Bottom-up resolution of functional enantiomers from self-organised monolayers (2008 – 2012)
  • EU Marie Curie Actions (EST) Development of biotechnology derived alternatives for sustainable detergents and innovative strategies of using sustainable ingredients by encapsulation and surfactant structuring. (BIOSEAL). (2005-2009)
  • IUAP: Protein structure and function in the post-genomic era

Spinoffs

ReMYND nv, www.remynd.be