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Cellular Biophysics

Marie-Pierre Rols

Group Leader

The main goal of our interdisciplinary group is to study the mechanisms of molecule delivery into cells and tissues by electric fields and to develop new tools for delivery, targeting and diagnostic. For that, we adapt and improve different complementary systems with increasing complexities (liposomes, cells in culture, spheroids and mice) and integrate various imaging tools to visualize and define membrane and cell permeabilization at the molecular level.

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We develop a multidisciplinary approach combining cell biology and biophysics to determine the mechanisms of membrane perturbations induced by transmembrane potential modifications, i.e. by the electroporation or electropermeabilization technique.These studies bring new approaches and guidelines for safe and efficient delivery of therapeutic molecules into cells and tissues since delivery requires targeting molecules towards specific cells.

In that context, and based on our previous works, the main objectives we pursued are:

•Elucidation of the mechanisms of electrotransfer: our works give evidence of the differences between the transfer of small molecules (bleomycin, cis-platinium), small oligonucleotides (siRNA, LNA), proteins and plasmid DNA and between the mechanisms involved in vitro on cells in culture (2-dimensional and 3-dimensional models) and in vivo on tissus (murine model).

•Development of new tools for delivery, targeting and diagnostic: our results have led us to define new types of electrical pulse generators and electrodes (adapted for study in vitro and in vivo models) and to adapt imaging systems (dorsal window chamber, fluorescence micro and macroscopies). In addition, we are developing other non-viral drug delivery approach based on lectin and we are using DNA aptamers that bind specifically to cancer cells. This approach has interests for Targeting of tumours (drug delivery) and Diagnostics (imaging of solid tumors).

 

We work in collaboration with laboratories worldwide in the context of several international networks (International Bioelectrics Consortium, COST Action TD1104: European network for development of electroporation-based technologies and treatments and LIA-EBAM: International Associated Laboratory on Pulsed Electric Fields Applications in Biology and Medicine). 

 

Main Publications

  • Josserand et al. (2016) .Electrochemotherapy guided by intraoperative fluorescence imaging for the treatment of inoperable peritoneal micro-metastases. J Control Release 233: 81-7
  • Pillet F et al. (2016). Cell wall as a target for bacteria inactivation by pulsed electric fields. Sci Rep 6: 19778
  • Gibot L et al. (2013). Antitumor drug delivery in multicellular spheroids by electropermeabilization. J Control Release 167: 138-47
  • Rosazza C et al. (2013). Intracellular tracking of single-plasmid DNA particles after delivery by electroporation. Mol Ther 21: 2217-26
  • Paganin-Gioanni A et al. (2011). Direct visualization at the single-cell level of siRNA electrotransfer into cancer cells. Proc Natl Acad Sci USA 108: 10443-7

 

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Biological systems of increasing complexities to unravel the mechanisms of molecules delivery into cells by electrotransfer, DNA aptamer and lectin.

 

Scientists

Marie-Pierre Rols

CNRS Research director

Laure Gibot

CNRS Research associate

Muriel Golzio

CNRS Research associate

Laurent Paquereau

Professor - University of Toulouse

Justin Teissié

CNRS Emeritus Research Director

Vincent Ecochard

Associate Professor - University of Toulouse

Research Assistants

Elisabeth Bellard

CNRS Engineer

Charlotte Da Silva

CNRS Fixed-term contract Engineer

Géraldine Gasc

CNRS Engineer

Laetitia Hellaudais

University of Toulouse Technician

Caroline Ladurantie

CNRS Technician

Post-doctoral Fellows

Agathe Figarol

Nathalie Joncker

Flavien Pillet

PhD Students

Mathilde Boce

Jean-François Guillet

Camille Lamarche

Moinecha Madi

Audrey Ric

Team Publications

2016

  • Gibot L., Rols M.P. (2016) Gene transfer by pulsed electric field is highly promising in cutaneous wound healing. Expert Opin Biol Th 16:67-77
  • Golzio, M. and J. Teissie (2016) Imaging of Electrotransferred siRNA. Methods Mol Biol 1372: 89-97
  • Madi M., Rols M.P., Gibot L. (2016) Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue. Curr Gene Ther. 16:75-82
  • Phez E., Gibot L., Rols M.P. (2016) How transient alterations of organelles in mammalian cells submitted to electric field may explain some aspects of gene electrotransfer process.Bioelectrochemistry S1567-5394:30013-5
  • Pillet F., Formosa-Dague C., Baaziz H., Dague E., Rols M.P. (2016) Cell wall as a target for bacteria inactivation by pulsed electric fields. Scientific reports 6:19778
  • Pillet, F., Marjanovic I., et al. (2016) Inactivation of spores by electric arcs. BMC Microbiol 16(1): 148

2015

  • Mauroy C., Rico-Lattes I., Teissie J., Rols M.P. (2015) Electric Destabilization of Supramolecular Lipid Vesicles Subjected to Fast Electric Pulses. Langmuir : the ACS journal of surfaces and colloids 31:12215-12222
  • Chabot, S., Teissie, J., and Golzio, M. (2015) Targeted electro-delivery of oligonucleotides for RNA interference: siRNA and antimiR. Adv Drug Deliv Rev 81:161-8
  • Chopinet, L., and Rols, M.P. (2015) Nanosecond electric pulses: a mini-review of the present state of the art. Bioelectrochemistry 103:2-6
  • Coustets, M., Ganeva, V., Galutzov, B., and Teissie, J. (2015) Millisecond duration pulses for flow-through electro-induced protein extraction from E. coli and associated eradication.Bioelectrochemistry 103:82-91
  • Madi, M., Rols, M.P., and Gibot, L. (2015) Efficient In Vitro Electropermeabilization of Reconstructed Human Dermal Tissue. J Membr Biol 248:903-8
  • Mauroy, C., Castagnos, P., Orio, J., Blache, M.C., Rico-Lattes, I., Teissie, J., Rols, M.P., and Blanzat, M. (2015). Versatile cellular uptake mediated by catanionic vesicles: simultaneous spontaneous membrane fusion and endocytosis. Mol Pharm 12:103-10

2014

  • Castagnos, P., I. Rico-Lattes, M. Blanzat, C. Mauroy, J. Orio, M. C. Blache, J. Teissie, and M. P. Rols. (2014) Versatile cellular uptake mediated by catanionic vesicles: simultaneous spontaneous membrane fusion and endocytosis. Molecular pharmaceutics
  • Escoffre, J. M., M. Hubert, J. Teissie, M. P. Rols, and C. Favard. (2014) Evidence for electro-induced membrane defects assessed by lateral mobility measurement of a GPi anchored protein. Eur Biophys J 43:277-286 43:277-286
  • Pasquet, L., E. Bellard, M. Golzio, M. P. Rols, and J. Teissie. (2014) A Double-Pulse Approach For Electrotransfection. J Membr Biol
  • Escoffre JM, Bellard E, Faurie C, Sébaï SC, Golzio M, Teissié J, Rols MP. (2014)Membrane disorder and phospholipid scrambling in electropermeabilized and viable cells. Biochim Biophys Acta1838:1701-1709
  • Gibot L, Lemelle A, Till U, Moukarzel B, Mingotaud AF, Pimienta V, Saint-Aguet P, Rols MP, Gaucher M, Violleau F, Chassenieux C, Vicendo P. (2014) Polymeric Micelles Encapsulating Photosensitizer: Structure/Photodynamic Therapy Efficiency Relation. Biomacromolecules 15:1443-1455
  • Martínez O, Bellard E, Golzio M, Mechiche-Alami S, Rols MP, Teissié J, Ecochard V, Paquereau L. (2014) Direct Validation of Aptamers as Powerful Tools to Image Solid Tumor. Nucleic Acid Ther24:217-225
  • Golzio, M. and Teissie J. (2014). siRNA delivery via electropulsation: a review of the basic processes. Methods Mol Biol 1121: 81-98
  • Teissie, J. and Golzio M. (2014). Direct imaging of siRNA electrotransfer at the single-cell level.Methods Mol Biol 1121: 121-130

2013

  • Rosazza C, Buntz A, Rieß T, Wöll D, Zumbusch A, Rols MP. (2013) Intracellular tracking of single-plasmid DNA particles after delivery by electroporation. Mol Ther. 21(12):2217-26
  • Orio J, Bellard E, Baaziz H, Pichon C, Mouritzen P, Rols MP, Teissié J, Golzio M, Chabot S. (2013) Sub-cellular temporal and spatial distribution of electrotransferred LNA/DNA oligomer. J RNAi Gene Silencing 9:479-85
  • Chabot S, Pelofy S, Teissié J, Golzio M. (2013) Delivery of RNAi-Based Oligonucleotides by Electropermeabilization. Pharmaceuticals (Basel) 10;6(4):510-21
  • Chopinet L, Batista-Napotnik T, Montigny A, Rebersek M, Teissié J, Rols M-P, Miklavčič D. (2013) Nanosecond electric pulses effects on gene expression. Journal of Membrane Biology 246(11):851-9
  • Gibot L, Auger FA, Lacroix D. (2013) The Pivotal Role of Vascularization in Tissue Engineering.Annu Rev Biomed Eng In press
  • Gibot L, Rols MP. (2013) 3D Spheroids’ Sensitivity to Electric Field Pulses Depends on Their Size. J Membr Biol 246(10):745-50
  • Chopinet L, Roduit C, Rols MP, Dague E. (2013) Destabilization induced by electropermeabilization analyzed by atomic force microscopy. Biochim Biophys Acta 1828(9):2223-9
  • Gibot L, Rols MP. (2013) Progress and Prospects: The Use of 3D Spheroid Model as a Relevant Way to Study and Optimize DNA Electrotransfer. Curr Gene Ther 13(3):175-81
  • Chabot S, Rosazza C, Golzio M, Zumbusch A, Teissié J, Rols MP. (2013) Nucleic acids electro-transfer: from bench to bedside. Curr Drug Metab 14(3):300-8
  • Chopinet L, Formosa C, Rols MP, Duval RE, Dague E. (2013) Imaging living cells surface and quantifying its properties at high resolution using AFM in QI™ mode. Micron 48:26-33
  • Gibot L, Wasungu L, Teissié J, Rols MP. (2013) Antitumor drug delivery in multicellular spheroids by electropermeabilization. J Control Release 167(2):138-147
  • Chabot S, Orio J, Schmeer M, Schleef M, Golzio M, Teissié J.(2013) Minicircle DNA electrotransfer for efficient tissue-targeted gene delivery. Gene Ther 20(1):62-8

2012

  • Bellard E, Markelc B, Pelofy S, Le Guerroué F, Sersa G, Teissié J, Cemazar M, Golzio M. (2012) Intravital microscopy at the single vessel level brings new insights of vascular modification mechanisms induced by electropermeabilization. J Control Release 163(3):396-403
  • Chabot S, Rosazza C, Golzio M, Zumbush A, Teissié J, Rols MP. (2012) Nucleic Acids Electro-transfer: From Bench to Bedside. Curr Drug Metab.
  • Portet T, Mauroy C, Démery V, Houles T, Escoffre JM, Dean DS, Rols MP. (2012) Destabilizing giant vesicles with electric fields: an overview of current applications. J Membr Biol. 245(9):555-64.
  • Escoffre JM, Nikolova B, Mallet L, Henri J, Favard C, Golzio M, Teissie J, Tsoneva I, Rols MP. (2012) New insights in the gene electrotransfer process: evidence for the involvement of the plasmid DNA topology. Curr Gene Ther. 12(5):417-22
  • Mauroy C, Portet T, Winterhalder M, Bellard E, Blache MC, Teissié J, Zumbusch A, Rols MP. (2012) Giant lipid vesicles under electric field pulses assessed by non invasive imaging.Bioelectrochemistry. 87:253-9
  • Pelofy S, Teissié J, Golzio M, Chabot S. (2012) Chemically modified oligonucleotide-increased stability negatively correlates with its efficacy despite efficient electrotransfer. J Membr Biol.245(9):565-71
  • Chabot S, Bellard E, Nielsen SJ, Orio J, Castanier R, Golzio M, Teissié J. (2012) LNA-based oligonucleotide electrotransfer for miRNA inhibition. Mol Ther. 20(8):1590-8
  • Escoffre JM, Rols MP. (2012) Electrochemotherapy: Progress and Prospects. Curr Pharm Des18(23):3406-15
  • Mauroy C, Castagnos P, Blache MC, Teissié J, Rico-Lattes I, Rols MP, Blanzat M. (2012) Interaction between GUVs and catanionic nanocontainers: new insight into spontaneous membrane fusion.Chem Commun 48(53):6648-50
  • Golzio M, Escoffre JM, Teissié J. (2012) shRNA-mediated gene knockdown in skeletal muscle.Methods Mol Biol 798:491-501
  • Teissié J, Escoffre JM, Paganin A, Chabot S, Bellard E, Wasungu L, Rols MP, Golzio M. (2012) Drug delivery by electropulsation: Recent developments in oncology. Int J Pharm 423(1):3-6
  • Rosazza C, Phez E, Escoffre JM, Cézanne L, Zumbusch A, Rols MP. (2012). Cholesterol implications in plasmid DNA electrotransfer: Evidence for the involvement of endocytotic pathways.Int J Pharm 423(1):134-43
  • Tamzali Y, Borde L, Rols MP, Golzio M, Lyazrhi F, Teissie J. (2012). Successful treatment of equine sarcoids with cisplatin electrochemotherapy: A retrospective study of 48 cases. Equine Vet J44(2):214-20

 

Download the complete list and the collaborative publications from 2016 to 2005

Valorisation

3rd Price of the 25th "concours innovation Midi-Pyrénées" , Section « laboratory and research teams » :

  • J.TEISSIE, MP. ROLS, M. GOLZIO, Y. TAMZALI, B.COUDERC. Device for eradication of horses cutaneous tumors by electrochemo- and electrogenotherapy.

Application for Technology Transfer : « Fluorescence imaging device for small animals (whole body)» Date of the comity : 20 Avril 2006. N° AV ou N° St DI 00745-01

  • The invention is a device which allows the study, by fluorescence imaging, of few centimeters objects. The inventive activity does not allow to apply for a patent : this is a combination of well-known elements that could be evident for an expert. However, this could be a skill, specially in micro biology.
  • The "Comité des Engagements" gave a favorable verdict to Technology transfer via "Licence de Savoir-Faire".

Patents

FR 1257125 (2012-07-23) SYSTEME DE DELIVRANCE A BASE DE LECTINE

Inventors :

  • LADURANTIE, Caroline; (FR).
  • GROSS, Grégory; (FR).
  • PAQUEREAU, Laurent; (FR).

(WO/2004/033491) PROTEINES INSECTICIDES ET/OU NEMATICIDES

Inventors :

  • CAYLEY, Patricia, Jane; (GB).
  • FOURNIER, Didier; (FR).
  • MACKAY, Elaine, Anne; (GB).
  • MACKAY, Katrina; (GB).
  • ONISKO, Bruce, Charles; (US).
  • PAQUEREAU, Laurent; (FR).

(WO/2001/000840) PROTEINES INSECTICIDES ET NEMATICIDES

Inventors:

  • FOURNIER, Didier; (FR).
  • PAQUEREAU, Laurent; (FR).
  • KLAEBE, Alain; (FR).
  • CHAVANT, Louis; (FR).

 

Collaborations

International

  • COST TD1104 European network for development of electroporation-based technologies and treatments (EP4Bio2Med):
    • MPR: Member of the management committee and Working Group 1 Leader
    • JT: member of the steering committee
  • International Bioelectrics Consortium (coordinator ODU Norfolk, R Heller):
    • MPR and JT: members of the management committee
  • European Associated Laboratory (LEA) “Pulsed Electric Fields Applications in Biology and Medicine:
    • MPR and JT: members of the management committee
  • FP7 oncomir network (coordinator Université de Gand, JC Marine)
  • FP7 eradication network (coordinator Jacobs University in Bremen, Pr. Lahore)
  • Institut of Oncology, Ljubljana (Pr. G Sersa)
  • Faculty of electrical engineering, Ljubljana (Pr. D Miklavcic)
  • University C Davila, Bucarest (Pr. M Moisescu)
  • MPI Golm (R Dimova)
  • University of Konstanz (Pr. Zumbusch)
  • Ming Hsieh Department of Electrical Engineering, Los Angeles CA, (Thomas Vernier)
  • Herlev Hospital, Copenhagen University (MD PhD, J Gehl)
  • Gabor Forgacs
  • Iana Tsoneva

National

  • CEA Gramat (Dr. R. Vezinet)
  • ITHPP Thegra (Dr. C Goepfert)
  • Université de Bordeaux (Dr. F. Couillaud)
  • Université de Bordeaux (Pr. D. Dean)
  • IGR CNRS, Villejuif (L Mir )
  • XLim CNRS (P Leveque)
  • ONERA, Palaiseau (JL Boulay)
  • IUT Laval, Université du Maine (V Blanckaert)
  • Cerpem, Laval (C Chomel)
  • Beta tech, l’Union
  • Anjou recherche, Maisons Lafitte (F David)
  • Université François-Rabelais, Tours, (Dr. Ayache Bouakaz)
  • Unité de Pharmacologie Chimique et Génétique et d’Imagerie, Paris ( Dr. Daniel Scherman)

Toulouse

  • Picometrics Technology (Dr J.C. Garcia)
  • Pierre Fabre Dermo-cosmetics (Dr. G. Josse)
  • French aerospace lab, ONERA (Dr X Orlik)
  • CRPA, CNRS UPS (Pr. Lasalle)
  • CCR, UPS (Pr. B Couderc)
  • Veterinary school, ENVT (Pr. Tamzali)
  • IMRCP, CNRS UPS (Dr. M Blanzat)
  • Coordination Chemistry lab, LCC, (Pr. Majoral)
  • IMRCP (Dr.Patricia Vicendo)
  • Laboratory for analysis and architecture of systems, LAAS (Dr. Etienne Dague)
  • LAAS (Dr. David Dubuc)

IPBS

  • A Milon, O Cuvillier, C Muller, I Maridonneau-Parini

Financial supports

Europe

  • 2008‐13 European agreement FP7 « Oncomir » coordinated by J Teissié 

Industry

  • 2013-16 CERPER contract with Pierre Fabre Dermo-cosmétique coordinated by M Golzio 
  • 2014-15 SAAT-ToulouseTechTransfert contract coordinated by L Paquereau
  • 2009‐12 ANR Procodd Debaciem contract coordinated by J Teissié 
  • 2009-2011 CERPER contract with Pierre Fabre Dermo-cosmétique coordinated by M Golzio

Public grants

  • 2014-17 Contrat "Region Midi Pyrénées" « CLE » coordinated by L Paquereau 
  • 2014-17 CIFRE with picometrics Technology company
  • 2013-17 Contract "ANR POLYTRANSFLOW" coordinated by MP Rols 
  • 2013-16 Contract "ANR ASTRID PIERGEN" coordinated by MP Rols 
  • 2013‐15 Contract "Région Midi Pyrénées" « EPICURE » coordinated by MP Rols
  • 2013-16 Contract "Région Midi Pyrénées" APRTCN coordinated by M Golzio
  • 2009-13 Contract "ANR COPOPDT" coordinated by P Vicendo (IMRCP, Toulouse)
  • 2012‐13 Contract "interrégional Midi Pyrénées/Aquitaine" « transfert de technologies » coordinated by M Golzio 
  • 2009-11 Contract "Région Midi-Pyrénées coordinated by L Paquereau 
  • 2009 RITC Labellisation, APTHERIM "Pôle de compétitivité" 
  • 2013-15 Partenariat Hubert Curien (PHC Cogito) EGIDE 
  • 2011-13 Partenariat Hubert Curien(PHC Proteus) EGIDE 
  • 2010-12 Partenariat Hubert Curien(PHC Procope) EGIDE 
  • 2008‐10 Contract "interrégional Midi Pyrénées/Aquitaine" coordinated by L Paquereau 
  • 2008‐10 Contract "Région Midi Pyrénées" « transfert de technologies » coordinated by J Teissie
  • 2006‐09 Contract "ANR DEET" coordinated by B Lapied (EA2647, Angers) 
  • 2006‐09 Contract "ANR Biodendridots" coordinated by AM Caminade (LCC, CNRS)
  • 2006‐09 Contract "ANR Cemibio" coordinated by P Leveque (XLIM CNRS)
  • 2006‐09 Contract "ANR CMIDT" coordinated by N Mignet (CNRS UMR8151)