Research
The Dynamic Bioimaging Lab specializes in deciphering the working of biomolecules and pathways from fluorescence data. We unravel cell-biological and disease-related mechanisms that cannot be studied via classical methods. We specialize in fluorescence method development and solving pressing life science questions.
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Research lines
The PhD researchers in the Dynamic Bioimaging Lab are working on specific Research Lines, where they exploit their expertise in time-resolved high-precision microscopy to provide detailed molecular insights no other research methods can match, as a basis for rational drug design or novel screening assays. For this, we collaborate with the UHasselt Neuroscience department or other researchers of the Biomedical Research Institute and Material Science Institute.
Biological phase separation and neurodegeneration
Our Lab is interested in understanding the physico-chemical principles that underlie biological phase separation, and with the research tools and expertise in fluorescence method development, we believe we are in a unique position to provide quantitative details about this fundamental biophysical subcellular organization principle.
We work on different membrane less organelle systems, one of which are aggregating proteins involved in neurodegeneration, in collaboration with Prof. Ilse Dewachter (UHasselt, Neurosciences). The process by which the aggregation is initiated is not yet fully understood. We propose that conformational changes are a key factor for a pathological protein depositions. Therefore we study in real-time the conformational changes from monomeric to aggregated proteins. Detailed knowledge on this would enable targeting the aggregating proteins in better ways.
Molecular insights in DNA repair pathways
DNA ligases catalyze the formation of phosphodiesters on the DNA backbone and are therefore essential enzymes for DNA metabolism, such as during replication and repair. Previous research resolved the conserved modular core structure of DNA ligases and implicated that large conformational changes take place during the catalytic cycle of DNA ligases. However, it is unknown how protein flexibility regulates the enzymatic turn-over rate and their ability to engage a set of substrate structures. In collaboration with Prof. David Wilson (UHasselt, Neurosciences), we test the hypothesis that structural dynamics of DNA ligases governs substrate selectivity and enzyme turn-over rate using single-molecule FRET (smFRET). This project will elucidate the relationship between structural dynamics of human DNA ligases and their enzymatic activity in order to understand their functioning in different cellular contexts. In addition to fundamental insights, the gained knowledge on conformational states of DNA ligases may facilitate the understanding of disease mechanisms and the development of specific inhibitors for targeted cancer therapy.
Novel targets for multidrug transporters
To tackle antibiotic resistance in bacteria, our Lab wants to understand how multidrug transporters recognize and expel different molecules and antibiotics out of the bacterial cell. We focus on both model proteins and homologues from pathogenic organisms in collaboration with Prof. Cedric Govaerts and Dr. Chloé Martens (Univ. Libre Bruxelles). To allow studying these membrane proteins in vitro under near-native conditions, we work on novel reconstitution methods in pore-spanning membrane devices. These micro-fabricated devices we generate using multi-photon lithography in collaboration with Prof. Ronald Thoelen (UHasselt IMO-IMOMEC).
Artificial cells via lipid nanotechnology
Membrane proteins are the main target for drug discovery, yet only a marginal fraction of structures have been solved. This is mainly because mimicking a natural membrane context compatible with structural investigations is extremely challenging. We hypothesize that reconstituting membrane proteins in microfluidic devices containing pore-spanning lipid membranes allows investigating their structure in a realtime manner compatible with high-throughput screening. We apply this technology to different model systems, such as the adenosine A2AAR. This GPCR plays important roles in the brain, the immune system and in different human diseases. This project provides a solid basis for future screening assays targeting G-protein coupled receptors.
Projects
To fund our core research lines, but also to stimulate collaborations with other research groups at UHasselt and other universities, the Lab can rely on different Research Projects.
MULTISCALE
In our FWO Heavy-Scale Infrastructure project MULTISCALE (2022-2026) we introduce light-sheet microscopy at UHasselt and apply it in diverse areas of the life sciences.
FBI-LIAISE
In our third FWO IRI project FBI-LIAISE (2023-2026) we enter Eurobioimaging as a member node, opening up imaging research infrastructure in Flanders to Europe and the World.
NATIVE
In our interdisciplinary FWO research project NATIVE (2021-2025) we combine single-molecule optical microscopy and lipid nanotechnology to decipher multidrug transport.
FLUOPATCH
In this BOF and FWO (Research grant) funded project FLUOPATCH (2017-2020) we combined patch clamp electrophysiology and single-molecule fluorescence to study Glycine receptors.
AOMC
With this FWO Medium-Scale Infrastructure project AOMC (2017-2020) we enable BIOMED to enter the world of super-resolution microscopy and found UHasselt's first core facility!
LEICASTED
In our FWO Heavy-Scale Infrastructure project LEICASTED (2016-2022) we introduced STED microscopy at KU Leuven and the Arenberg imaging facility.
SIGNALCASC
In our BOF project SIGNALCASC (2016-2021) we develop novel single-molecule fluorescence methods to study signaling pathways such as ErbB/EGFR and Glycine receptors.
PIEFLIM
In this FWO Research Project PIEFLIM (2015-2018) we develop multicolor time-resolved imaging and apply it to studying bacterial protein translocation and HIV.
2023
2023
Luginina A, Maslov I, Khorn P, Volkov O, Khnykin A, Kuzmichev P, Shevtsov M, Belousov A, Kapranov I, Dashevskii D, Kornilov D, Bestsennaia E, Hofkens J, Hendrix J, Gensch T, Cherezov V, Ivanovich V, Mishin A, Borshchevskiy V., Functional GPCR Expression in Eukaryotic LEXSY System, J Mol Biol., 2023, Dec 1; 435(23):168310
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Coucke Q, Parveen N, Fernández GS, Qian C, Hofkens J, Debyser Z, Hendrix J., Particle-based phasor-FLIM-FRET resolves protein-protein interactions inside single viral particles, Biophys Rep (N Y). 2023 Aug 9;3(3):100122
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Agam G, Gebhardt C, Popara M, Mächtel R, Folz J, Ambrose B, Chamachi N, Chung SY, Craggs TD, de Boer M, Grohmann D, Ha T, Hartmann A, Hendrix J, Hirschfeld V, Hübner CG, Hugel T, Kammerer D, Kang HS, Kapanidis AN, Krainer G, Kramm K, Lemke EA, Lerner E, Margeat E, Martens K, Michaelis J, Mitra J, Moya Muñoz GG, Quast RB, Robb NC, Sattler M, Schlierf M, Schneider J, Schröder T, Sefer A, Tan PS, Thurn J, Tinnefeld P, van Noort J, Weiss S, Wendler N, Zijlstra N, Barth A, Seidel CAM, Lamb DC, Cordes T., Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins, Nat Methods. 2023 Apr;20(4):523-535
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Ivan Maslov, Oleksandr Volkov, Polina Khorn, Philipp Orekhov, Anastasiia Gusach, Pavel Kuzmichev, Andrey Gerasimov, Aleksandra Luginina, Quinten Coucke, Andrey Bogorodskiy, Valentin Gordeliy, Simon Wanninger, Anders Barth, Alexey Mishin, Johan Hofkens, Vadim Cherezov, Thomas Gensch, Jelle Hendrix*, Valentin Borshchevskiy*, "Sub-millisecond conformational dynamics of the A2A adenosine receptor revealed by single-molecule FRET" Communications Biology, 2023 Apr 3;6(1):362
2022
2022
2021
2021
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Sören Kuypers, Nick Smisdom, Isabel Pintelon, Jean-Pierre Timmermans, Marcel Ameloot, Luc Michiels, Jelle Hendrix*, Baharak Hosseinkhani*, "Unsupervised Machine Learning-Based Clustering of Nanosized Fluorescent Extracellular Vesicles" Small, 2021, 17, 2006786
2020
2020
Susana Rocha, Jelle Hendrix, Doortje Borrenberghs, Zeger Debyser, Johan Hofkens, "Imaging the Replication of Single Viruses: Lessons Learned from HIV and Future Challenges To Overcome" ACS Nano, August 2020, 14, 9, 10775–10783
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Simone Giovannozzi, Veerle Lemmens, Jelle Hendrix, Rik Gijsbers, Rik Schrijvers, "Live cell imaging demonstrates multiple routes towards a STAT1 gain-of-function phenotype" Front. Immunol. June 2020, 11:1114.
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Hedvig Tamman°, Katleen Van Nerom°, Hiraku Takada, Niels Vandenberk, Daniel Scholl, Yury Polikanov, Johan Hofkens, Ariel Talavera, Vasili Hauryliuk*, Jelle Hendrix* and Abel Garcia-Pino*, "A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes" (Nat Chem Biol, May 11)
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Veerle Lemmens, Keerthana Ramanathan, Jelle Hendrix, "Fluorescence microscopy data for quantitative mobility and interaction analysis of proteins in living cells" Data in Brief, 29, April 2020, 105348
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Irena Zurnic Bönisch, Lieve Dirix, Veerle Lemmens, Doortje Borrenberghs, Flore De Wit, Frank Vernaillen, Susana Rocha, Frauke Christ, Jelle Hendrix, Johan Hofkens, Zeger Debyser, "Capsid Labelled HIV to Investigate the Role of Capsid During Nuclear Import and Integration" Journal of Virology, April 2020 Volume 94 Issue 7 e01024-19
2019
2019
Longfils M*, Smisdom N, Ameloot M, Rudemo M, Lemmens V, Solís Fernandez G, Röding M, Lorén N, Hendrix J*, Särkkä, A, "Raster Image Correlation Spectroscopy Performance Evaluation"Biophysical journal, Volume 117, Issue 10, 19 November 2019, Pages 1900-1914
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Harshita Bhatia, Julian A. Steele, Cristina Martin, Masoumeh Keshavarz, Guillermo Solis-Fernandez, Haifeng Yuan, Guillaume Fleury, Haowei Huang, Iurii Dovgaliuk, Dmitry Chernyshov, Jelle Hendrix, Maarten B. J. Roeffaers, Johan Hofkens, Elke Debroye, "Single-Step Synthesis of Dual Phase Bright Blue-Green Emitting Lead Halide Perovskite Nanocrystal Thin Films"Chemistry of Materials, Volume: 31 Issue: 17 Pages: 6824-6832, Sep 10, 2019
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Huang H, Yuan H, Zhao J, Solís-Fernández G, Zhou C, Seo JW, Hendrix J, Steele J, Hofkens J, Long J, Roeffaers M, "C(sp3)-H Bond Activation by Perovskite Solar Photocatalyst Cell"ACS Energy Letters, 2019, 4(1):203–208
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Vandenberk N, Karamanou S, Portaliou AG, Zorzini A, Hofkens J, Hendrix J*, Economou A*, "The preprotein binding domain of SecA displays intrinsic rotational dynamics."Structure. 2019 January 2; 27(1):90-101.e6.
2018-2015
2018-2015
Barth A, Hendrix J, Fried D, Barak Y, Bayer EA, Lamb DC*, "Dynamic interactions of type I cohesin modules fine-tune the structure of the cellulosome of Clostridium thermocellum"Proceedings of the National Academy of Sciences USA. 2018 November 14; 115(48):E11274-E11283.
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Borrenberghs D, Dirix L, Cereseto A, Hofkens J, Debyser Z* and Hendrix J* , "Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration"Nucleic Acids Research. 2018 November 16; 47(3):1195–1210.
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Hellenkamp B°, Schmid S°, Adariani SR, Ambrose B, Aznauryan M, Barth A, Birkedal V, Bowen ME, Chen H, Cordes T, Eilert T, Fijen C, Gebhardt C, Götz M, Gouridis G, Gratton E, Ha T, Hao P, Hanke CA, Hartmann A, Hendrix J, Hildebrandt LL, Hirschfeld V, Hohlbein J, Hua B, Hübner CG, Kallis E, Kapanidis AN, Kim JY, Krainer G, Lamb DC, Lee NK, Lemke EA, Levesque B, Levitus M, McCann JJ, Naredi-Rainer N, Nettels D, Ngo T, Qiu R, Robb NC, Röcker C, Sanabria H, Schlierf M, Schröder T, Schuler B, Seidel H, Streit L, Thurn J, Tinnefeld P, Tyagi S, Vandenberk N, Vera AM, Weninger KR, Wünsch B, Yanez-Orozco IS, Michaelis J*, Seidel CAM*, Craggs TD* and Hugel T, "Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study"Nature Methods 2018, 15:669–676
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Parveen N, Borrenberghs D, Rocha S, Hendrix J*, "Single Viruses on the Fluorescence Microscope: Imaging Molecular Mobility, Interactions and Structure Sheds New Light on Viral Replication."Viruses. May 10 2018. 10(5) pii: E250.
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Schrimpf W°, Barth A°, Hendrix J and Lamb DC, "PAM: A Framework for Integrated Analysis of Imaging, Single-Molecule, and Ensemble Fluorescence Data."Biophysical Journal, April 10, 2018, 114 (7), p1518-1528.
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Huang H, Yuan H, Janssen KPF, Solis-Fernandez G, Wang Y, Tan CYX, Jonckheere D, Debroye E, Long JL, Hendrix J, Hofkens J, Steele JA, Roeffaers, MBJ., "Efficient and Selective Photocatalytic Oxidation of Benzylic Alcohols with Hybrid Organic-Inorganic Perovskite Materials."ACS Energy Letters, May 2018, 3(4), pp755-759
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Talavera A°, Hendrix J°, Versées W, Jurėnas D, Van Nerom K, Vandenberk N, Singh RK, Konijnenberg A, De Gieter S, Castro-Roa D, Barth A, De Greve H, Sobott F, Hofkens J, Zenkin N, Loris R, Garcia-Pino A,"Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors."Science Advances. 2018 Mar 14; 4(3), eaap9714
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Vandenberk N, Barth A, Borrenberghs D, Hofkens J, Hendrix J, "Evaluation of Blue and Far-Red Dye Pairs in Single-Molecule Förster Resonance Energy Transfer Experiments."J. Phys. Chem. B. March 15, 2018; 122(15), pp 4249–4266
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Schrimpf W°, Lemmens V°, Smisdom N, Ameloot M, Lamb DC*, Hendrix J*, "Crosstalk-free multicolor RICS using spectral weighting."Methods. 2018 May 1;140-141:97-111
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Rosam M, Krader D, Nickels C, Hochmair J, Back KC, Agam G, Barth A, Zeymer C, Hendrix J, Schneider M, Antes I, Reinstein J, Lamb DC, Buchner J., "Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate."Nat Struct Mol Biol. 2018 Jan;25(1):90-100.
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Burger VM, Vandervelde A, Hendrix J, Konijnenberg A, Sobott F, Loris R, Stultz CM.,"Hidden States within Disordered Regions of the CcdA Antitoxin Protein."J Am Chem Soc. 2017 Feb 22;139(7):2693-2701
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Borrenberghs D, Dirix L, De Wit F, Rocha S, Blokken J, De Houwer S, Gijsbers R, Christ F, Hofkens J, Hendrix J*, Debyser Z*, "Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry."Sci Rep. 2016 Nov 10;6:36485
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Hendrix J*, Dekens T, Schrimpf W, Lamb DC*, "Arbitrary-Region Raster Image Correlation Spectroscopy."Biophys J. 2016 Oct 18;111(8):1785-1796
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Hendrix J, Baumgärtel V, Schrimpf W, Ivanchenko S, Digman MA, Gratton E, Kräusslich HG, Müller B, Lamb DC.,“Live-cell observation of cytosolic HIV-1 assembly onset reveals RNA-interacting Gag oligomers.”.J Cell Biol. 2015 Aug 17;210(4):629-46
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Röhl A, Wengler D, Madl T, Lagleder S, Tippel F, Herrmann M, Hendrix J, Richter K, Hack G, Schmid AB, Kessler H, Lamb DC, Buchner J.,“Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules.”.Nat Commun. 2015 Apr 8;6:6655
2014-2006
2014-2006
Ozgen H, Schrimpf W, Hendrix J, de Jonge JC, Lamb DC, Hoekstra D, Kahya N, Baron W., “The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix.”. PLoS One. 2014 Jul 8;9(7):e101834
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Borrenberghs D, Thys W, Rocha S, Demeulemeester J, Weydert C, Dedecker P, Hofkens J, Debyser Z*, Hendrix J*., “HIV virions as nanoscopic test tubes for probing oligomerization of the integrase enzyme.”. ACS Nano. 2014 Apr 22;8(4):3531-45
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Hendrix J°, van Heertum B°, Vanstreels E, Daelemans D, De Rijck J., “Dynamics of the ternary complex formed by c-Myc interactor JPO2, transcriptional co-activator LEDGF/p75, and chromatin.”. J Biol Chem. 2014 May 2;289(18):12494-506
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Hendrix J, Lamb DC., “Implementation and application of pulsed interleaved excitation for dual-color FCS and RICS.”. Methods Mol Biol. 2014;1076:653-82
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Hendrix J*, Schrimpf W, Höller M, Lamb DC*., “Pulsed interleaved excitation fluctuation imaging.”.Biophys J. 2013 Aug 20;105(4):848-61
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De Graeve S, Marinelli S, Stolz F, Hendrix J, Vandamme J, Engelborghs Y, Van Dijck P, Thevelein JM.,“Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system.”. Biochem J. 2013 Nov 1;455(3):295-306
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Desimmie BA, Schrijvers R, Demeulemeester J, Borrenberghs D, Weydert C, Thys W, Vets S, Van Remoortel B, Hofkens J, De Rijck J, Hendrix J, Bannert N, Gijsbers R, Christ F, Debyser Z., “LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions.”. Retrovirology. 2013 May 30;10:57
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Hendrix J, Lamb DC., “Pulsed interleaved excitation: principles and applications.”. Methods Enzymol. 2013;518:205-43
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Desimmie BA, Humbert M, Lescrinier E, Hendrix J, Vets S, Gijsbers R, Ruprecht RM, Dietrich U, Debyser Z, Christ F., “Phage display-directed discovery of LEDGF/p75 binding cyclic peptide inhibitors of HIV replication.”. Mol Ther. 2012 Nov;20(11):2064-75
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McNeely M°, Hendrix J°, Busschots K, Boons E, Deleersnijder A, Gerard M, Christ F, Debyser Z., “In vitro DNA tethering of HIV-1 integrase by the transcriptional coactivator LEDGF/p75.”. J Mol Biol. 2011 Jul 29;410(5):811-30
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Cuyvers S, Hendrix J, Dornez E, Engelborghs Y, Delcour JA, Courtin CM., “Both substrate hydrolysis and secondary substrate binding determine xylanase mobility as assessed by FRAP.”. J Phys Chem B. 2011 Apr 28;115(16):4810-7
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Hendrix J, Gijsbers R, De Rijck J, Voet A, Hotta J, McNeely M, Hofkens J, Debyser Z, Engelborghs Y.,“The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering.”. Nucleic Acids Res. 2011 Mar;39(4):1310-25
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Nath S, Meuvis J, Hendrix J, Carl SA, Engelborghs Y., “Early aggregation steps in alpha-synuclein as measured by FCS and FRET: evidence for a contagious conformational change.”. Biophys J. 2010 Apr 7;98(7):1302-11
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Řičicová M, Kucharíková S, Tournu H, Hendrix J, Bujdáková H, Van Eldere J, Lagrou K, Van Dijck P.,“Candida albicans biofilm formation in a new in vivo rat model.”. Microbiology. 2010 Mar;156(Pt 3):909-919
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Briers Y, Schmelcher M, Loessner MJ, Hendrix J, Engelborghs Y, Volckaert G, Lavigne R., “The high-affinity peptidoglycan binding domain of Pseudomonas phage endolysin KZ144.”. Biochem Biophys Res Commun. 2009 May 29;383(2):187-91
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Bartholomeeusen K, Christ F, Hendrix J, Rain JC, Emiliani S, Benarous R, Debyser Z, Gijsbers R, De Rijck J., “Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZ.”. J Biol Chem. 2009 Apr 24;284(17):11467-77
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Hendrix J, Flors C, Dedecker P, Hofkens J, Engelborghs Y., “Dark states in monomeric red fluorescent proteins studied by fluorescence correlation and single molecule spectroscopy.”. Biophys J. 2008 May 15;94(10):4103-13
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Buyens K, Lucas B, Raemdonck K, Braeckmans K, Vercammen J, Hendrix J, Engelborghs Y, De Smedt SC, Sanders NN., “A fast and sensitive method for measuring the integrity of siRNA-carrier complexes in full human serum.”. J Control Release. 2008 Feb 18;126(1):67-76
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Hombrouck A, De Rijck J, Hendrix J, Vandekerckhove L, Voet A, De Maeyer M, Witvrouw M, Engelborghs Y, Christ F, Gijsbers R, Debyser Z., “Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV.”. PLoS Pathog. 2007 Mar;3(3):e47
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De Rijck J, Vandekerckhove L, Gijsbers R, Hombrouck A, Hendrix J, Vercammen J, Engelborghs Y, Christ F, Debyser Z., “Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication.”. J Virol. 2006 Dec;80(23):11498-509
Equipment
For carrying out our research, the Dynamic Bioimaging Lab has access to many microscopes...
- We house both widefield, confocal and light-sheet systems,
- We image single molecules and cells but also larger systems,
- We record data from the picoseconds to real time,
- We go from the Ångstrom to centimeter length scale,
- We analyse steady state or fluctuating fluorescence signals, and
- We record label-free and spectrally resolved samples.
The Advanced Optical Microscopy Centre web page lists the different instruments.
Facilities
The Dynamic Bioimaging Lab is located in the Biomedical Research Institute that provides the necessary services and facilities for our research.
Contact
prof. dr. Jelle HENDRIX
Agoralaan C (BIOMED), B3590 Diepenbeek
Business Development
Agoralaan C (BIOMED), B3590 Diepenbeek