Plasmonic DNA: Towards Genetic Diagnosis Chips

"Plasmonics and DNA" special issueInternational audienc

Caractéristiques Optiques et Dynamiques d'Interactions Biomoléculaires de Surface - Application aux biopuces à ADN

As medical science advances towards the generalisation of predictive methods, biosensors are taking on the lead role. Based on a variety of detection and transduction methods, different biosensors are being developed in order to observe biomolecular interactions. The scope of application is vast: detection of pollutants or genetically modified organisms, improvement of drug specificity (anti-cancer treatment) or reliable genetic diagnosis. My research is focused on the detection of the Cystic Fibrosis genetic disease. The biosensor that we used relies on an optical system using SPR imaging coupled to a DNA biochip. The probe molecules are single strands of synthesized DNA whose sequence was calculated in order to be able to detect, in the patient's target DNA single strands, the genetic modifications of the CFTR gene responsible for the disease. These biochips consist of a metallic layer functionalized by surface chemistry based on the thiol/gold bond and ending in a layer of Streptavidin. The probes are biotinilyzed and a micro-arrayer spots them out in the form of a matrix on the surface. Through the implementation of a temperature control module and various studies on the TM of DNA-DNA interactions, along with a data correction method, we succeeded in establishing the genetic diagnosis of a SNP without ambiguity in around ten minutes. The last studies of this document pave the way to the experimental cartography of the secondary structures of target single strands.A l'heure où la médecine tend vers une généralisation des méthodes prédictives, les biocapteurs occupent le devant de la scène. Se basant sur des méthodes de détection et de transduction variées, différents types de biocapteurs sont développés dans le but d'observer des interactions biomoléculaires. Les domaines d'application sont vastes : détections de polluants ou d'OGM, amélioration de la spécificité d'un médicament (traitement anti-cancéreux) ou encore diagnostic génétique fiable. C'est autour de la problématique de la détection de la maladie génétique de la mucoviscidose que s'architecture mes travaux de recherche. Le biocapteur que nous avons utilisé se base sur un système optique utilisant l'imagerie SPR couplée à une biopuce à ADN. Les molécules sondes sont des simples brins d'ADN de synthèse dont la séquence a été calculée afin de pouvoir détecter dans les simples brins cibles issus de l'ADN de patient les modifications génétiques du gène de la CFTR responsable de la maladie. Ces biopuces sont constituées d'une couche métallique fonctionnalisée par une chimie de surface reposant sur la liaison thiol/or et se terminant par une couche de Streptavidin. Les sondes sont biotinylées et un micro-arrayer les dispose sous forme de matrice sur la surface. Grâce à l'implémentation d'un module de contrôle de température et de différentes études sur le TM des interactions ADN-ADN et grâce à une méthode de correction des données, nous avons réussi à établir le diagnostic génétique d'une SNP sans ambiguïté en moins d'une dizaine de minutes. Les dernières études de ce manuscrit ouvrent la porte à la cartographie expérimentale des structures secondaires des simples brins cibles

Temperature impact on thermodynamical parameters of DNA:DNA hybridization kinetics as quantified by Surface Plasmon Resonance Imaging (SPRI) system

International audienc

GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target

Glycogen synthase kinase 3 (GSK3) is a key regulator of many cellular signaling processes and performs a wide range of biological functions in the nervous system. Due to its central role in numerous cellular processes involved in cell degeneration, a rising number of studies have highlighted the interest in developing therapeutics targeting GSK3 to treat neurodegenerative diseases. Although recent works strongly suggest that inhibiting GSK3 might also be a promising therapeutic approach for retinal degenerative diseases, its full potential is still under-evaluated. In this review, we summarize the literature on the role of GSK3 on the main cellular functions reported as deregulated during retinal degeneration, such as glucose homeostasis which is critical for photoreceptor survival, or oxidative stress, a major component of retinal degeneration. We also discuss the interest in targeting GSK3 for its beneficial effects on inflammation, for reducing neovascularization that occurs in some retinal dystrophies, or for cell-based therapy by enhancing Müller glia cell proliferation in diseased retina. Together, although GSK3 inhibitors hold promise as therapeutic agents, we highlight the complexity of targeting such a multitasked kinase and the need to increase our knowledge of the impact of reducing GSK3 activity on these multiple cellular pathways and biological processes

Biochip data normalization using multifunctional probes

International audienc

Surface plasmon resonance imaging biochip system - application to genotyping

WorkshopInternational audienc

Systèmes de biopuces et plasmonique - exemple d'application au diagnostic génétique

WorkshopInternational audienc

Self-calibrated dynamical optical biochip system using surface plasmon resonance imaging: application to genotyping

International audienc

Self-calibration procedure for temperature stabilized dynamical biochips - example of accurate genetic diagnosis

International audienc

Optical Biochip System using Surface Plasmon Resonance Imaging (SPRI) - Application to Genotyping and influence of Temperature

International audienc