Microarrays for diagnosis and drug discovery

Microarrays consist of a supporting material at the surface of which molecules are immobilized in an ordered array. Immobilized molecules can be DNA, protein, carbohydrate, cells… Microarrays allow studying simultaneously several tens to several thousands of biomolecular interactions with minute amounts of samples.The base material of our microarray consists in microstructured borosilicate glass slide featuring 40 microwells.Biomolecules are printed at the bottom of each microwell thanks to a peiezoelectric delivering system. Each microwell can be regarded as an independent microarray allowing 40 independent experiments to be carried on a single glass slide. Our microarrays are exploited for cancer diagnosis and anti-infectious drug discovery.

  • Drug discovery of anti-infectious molecules:

Pseudomonas aeruginosa (PA) is a gram negative opportunistic pathogen. It is one of the three most prevalent nosocomial bacterial pathogens (10-30% of nosocomial infections) and is the major cause of morbidity and mortality of cystic fibrosis patient. Colonization of the upper respiratory tract by PA often leads to chronic inflammation and eventually to death despite aggressive antibiotic therapy. Indeed, the emergence of resistant strains and biofilm formation seems to give a selective advantage to the bacterium. A promising approach is to inhibit the virulence factors of PA and particularly adhesins and lectin involved in the bacterial adhesion or biofilm formation. Lectins are carbohydrate binding molecules. They are not enzymes or anti-bodies. PA lectins interact with carhydrates displayed at the surface of the tissues. Our objective is to find high affinity molecules for PA lectins that will inhibit its interaction with their natural ligands. To this aim our colleagues (IBMM) synthesized multivalent molecules displaying 2 to 12 carbohydrates. These molecules are called glycoclusters. Our microarrays allow measuring lectin/glycocluster Kds and IC50 with only a few tens of picomoles. These microarray binding studies are completed by molecular simulation and in-vitro testing (UGSF).

Contact Yann Chevolot
Collaboration : Université de Montpellier (Institut Max Mousseron des Biomolécules), Université de Lille (Unité de Glycobiologie Fonctionnelle et Structurale), Université de Lyon (Institut de Chimie Biochimie Moléculaire et Supramoléculaire), Elicityl.

  • Cancer diagnosis:

During the last thirty year, the number of cancer case has nearly doubled worldwide and cancer is becoming the first cause of mortality in the world. Nowadays, cancer diagnosis is mainly based on imaging techniques in combination with cytology and the detection of a single biomarker. However due to the natural variability, the diagnosis and the follow-up of patient based on a single biomarker is usually not reliable enough. In this context, microarrays allow identifying and following simultaneously several tens of biomarkers. In the aim of providing a reliable, sensitive and specific diagnosis for breast and colorectal cancers, we have developed dedicated protein microarray. For each protein the surface chemistry has been optimized leading to a detection limit of 10 pM (to be compared to a detection limit in the nM range with ELISA), and an occurrence over 80% of patient sera by combining the detection of 5 biomarkers (10-40 % with a single biomarker based diagnosis).

Contact : Emmanuelle Laurenceau
Collaboration : CHU de St-Etienne, CHU Montpellier, Ecole des Mines de St-Etienne, bioMérieux.

INL CNRS
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