Determining the subcellular targets and signaling cascades activated by nanosecond pulsed electric fields

Sujets de thèse 2013

Intitulé de la thèse
Determining the subcellular targets and signaling cascades activated by nanosecond pulsed electric fields
Publication du sujet sur le site de l’ABG : NON
Nature du financement : Financement institutionnel, Contrat Doctoral, Financement régional, Contrats université sur projets,)
Domaine de compétences principal (pour l’ABG) : Biologie, médecine, santé
Domaine de compétences secondaire (pour l’ABG) : Sciences pour l’Ingénieur
Spécialité de doctorat : Electronique des hautes fréquences, Photonique et Systèmes

Lieu de travail
XLIM, Faculté des Sciences et Techniques
Limoges
Laboratoire d’accueil : XLIM/OSA

Présentation de l’équipe de recherche
Ce sujet de thèse s’inscrit
dans la chaire santé-biophysique, portée par Rod O’Connor à l’interface avec le projet bioélectrophotonique de l’institut de recherche XLIM.
Le groupe est constitué de deux à trois permanents dans chaque domaine

Résumé de la thèse en français
Nanosecond pulsed electric fields (nsPEFs) are a promising new tool for manipulating cell physiology with a number of potential biomedical applications including cancer therapeutics and tissue engineering. The precise target for nsPEF within the cell are unknown; however, simulations and previous experiments suggest organellar structures may be permeabilized or disrupted, leading to apoptosis and cell death through caspase-dependent and caspase-independent pathways. Whilst this apoptotic response appears to emerge at the highest intensities examined (10kV/cm), at lower intensities more subtle effects appear to involve changes in intracellular calcium signaling, cAMP, JNK and several other signaling cascades. There is currently no working hypothesis of how such fields may couple to cell physiology or molecular signalling, beyond the physical effects on membrane integrity (electroporation or permeabilization) observed at high intensities. The thesis project will examine the potential role of a newly discovered voltage signaling pathway in mammalian cells that may be responsible for the multiple signaling pathways activated by nsPEFs. The project will employ methods in cellular and molecular biology, live cell imaging and flow cytometry to probe cellular signaling cascades activated by nsPEFs.

Résumé de la thèse en anglais
Nanosecond pulsed electric fields (nsPEFs) are a promising new tool for manipulating cell physiology with a number of potential biomedical applications including cancer therapeutics and tissue engineering. The precise target for nsPEF within the cell are unknown; however, simulations and previous experiments suggest organellar structures may be permeabilized or disrupted, leading to apoptosis and cell death through caspase-dependent and caspase-independent pathways. Whilst this apoptotic response appears to emerge at the highest intensities examined (10kV/cm), at lower intensities more subtle effects appear to involve changes in intracellular calcium signaling, cAMP, JNK and several other signaling cascades. There is currently no working hypothesis of how such fields may couple to cell physiology or molecular signalling, beyond the physical effects on membrane integrity (electroporation or permeabilization) observed at high intensities. The thesis project will examine the potential role of a newly discovered voltage signaling pathway in mammalian cells that may be responsible for the multiple signaling pathways activated by nsPEFs. The project will employ methods in cellular and molecular biology, live cell imaging and flow cytometry to probe cellular signaling cascades activated by nsPEFs.

Description complète du sujet de thèse
Nanosecond pulsed electric fields (nsPEFs) are a promising new tool for manipulating cell physiology with a number of potential biomedical applications including cancer therapeutics and tissue engineering. The precise target for nsPEF within the cell are unknown; however, simulations and previous experiments suggest organellar structures may be permeabilized or disrupted, leading to apoptosis and cell death through caspase-dependent and caspase-independent pathways. Whilst this apoptotic response appears to emerge at the highest intensities examined (10kV/cm), at lower intensities more subtle effects appear to involve changes in intracellular calcium signaling, cAMP, JNK and several other signaling cascades. There is currently no working hypothesis of how such fields may couple to cell physiology or molecular signalling, beyond the physical effects on membrane integrity (electroporation or permeabilization) observed at high intensities. The thesis project will examine the potential role of a newly discovered voltage signaling pathway in mammalian cells that may be responsible for the multiple signaling pathways activated by nsPEFs. The project will employ methods in cellular and molecular biology, live cell imaging and flow cytometry to probe cellular signaling cascades activated by nsPEFs.

Objectifs scientifiques de la thèse
quels sont les effets de impulsions de champs électromagnétiques
nanosecondes et subnanosecondes sur le vivant.

Compétences à l’issue de la thèse
bioélectromagnétisme
biophotonique
biologie
microdosimétrie

Mots clés (séparés par des virgules)
bioélectromagnétisme
biophotonique
biologie
microdosimétrie
Conditions restrictive de candidature (nationalité, âge, …) : NON

Expérience/profil souhaité(e)
biologie cellulaire
bioélectromagnétisme

Directeur de thèse
Dr Rod O’Connor
Adresse mail du directeur de thèse : neurophoton@gmail.com
Téléphone Directeur de thèse : +33 5 87 50 67 53

Co-directeur de thèse
Philippe LEVEQUE
Adresse mail du co-directeur de thèse : philippe.leveque@unilim.fr
Téléphone co-Directeur de thèse : 33587506753
Cofinancement LABEX SigmaLIM demandé : OUI

Justification du cofinancement LABEX
thèse chaire Santé biophysique
Thématique LABEX concernée : Thème 6: Santé
Thèse pour Action transverse : OUI

Action transverse concernée et justification
projet bioélectrophotonique

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