MOOC « ouvrez les portes du laboratoire: cellules et cellules souches » MOOC: Massive Open Online Course: formation en ligne ouverte à tous https://www.fun-mooc.fr/courses/univnantes/31004S03/session04/about Enseignement en ligne, inscriptions gratuites Parcours « Avancé »: Le déroulement d’un projet de recherche de A à Z : de l’hypothèse scientifique à la publication (vidéos « fil rouge ») Lectures d’article scientifique Réseaux biologiques et de biologie des systèmes Les articles présentés dans le parcours avancé peuvent être proposés à l’examen final+++ (= à lire et connaître comme les articles vus en cours) Début des cours: jeudi 31 août (8 semaines en tout)

La recherche translationnelle l’institut du thorax

Recherche translationnelle Définition : translation = traduction du chercheur au lit du malade et inversement pour le bénéfice de tous (pont entre la recherche fondamentale et préclinique d’une part et la recherche clinique d’autre part)

Exemple 2: traitement du cancer FIGURE 2 | Comprehensive clinical decision-making algorithm. From the following article: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Christos Sotiriou & Martine J. Piccart Nature Reviews Cancer 7, 545-553 (July 2007) The ultimate goal will be to integrate several potential clinically relevant parameters into a comprehensive clinical decision-making algorithm that will lead us towards individualized medicine. This algorithm should include traditional clinico-pathological parameters that survive multivariate analysis and incorporate data generated by using the new molecular tools. It must integrate what genomics, genetics and proteomics tell us not only about the tumour but also about the host, and include better information about tumour staging, including the assessment of circulating tumour cells and modern molecular imaging. Pourquoi un même traitement donné aux « mêmes » patients donne des résultats différents?

Recherche de biomarqueurs pronostiques Biomarqueur: marqueur biologique d’une maladie, d’un stade d’évolution, de pronostic (dosage d’une protéine, profil génique, etc.) Box 1 | Microarray technology. Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Christos Sotiriou & Martine J. Piccart. Nature Reviews Cancer 7, 545-553 (July 2007) The concept behind DNA chip or microarray technology relies on the accurate binding, or hybridization, of strands of DNA with their precise complementary copies in experimental conditions where one sequence is also bound onto a solid-state substrate73. At present there are several DNA microarray platforms used for genome-wide gene-expression studies. The oligonucleotide-based microarrays are popular10, 74. There are two major approaches to constructing oligonucleotide arrays: in the first, microarrays composed of short oligonucleotides (25 bases) are synthesized directly onto a solid matrix using photolithographic technology (Affymetrix). Alternatively, microarrays composed of long oligonucleotides (55–70 bases) can either be deposited by an ink-jet printing process (Agilent) or spotted by a robotic printing process onto glass slides (CodeLink). The Affymetrix microarray system uses a single-colour detection scheme, whereby one sample is hybridized per chip. Agilent technology uses a two-colour scheme, whereby the same array is hybridized with two different samples. RNA is extracted from frozen breast tumour samples collected either at surgery (a), or before treatment (b), labelled with a detectable marker (fluorescent dye), and hybridized to the array containing individual gene-specific probes. Gene-expression levels are estimated by measuring the fluorescent intensity for each gene probe. A gene-expression vector is then collected by summarizing the expression levels of each gene in the sample. To facilitate the comparison between the different experiments and compensate for differences in labelling, hybridizations and detection methods, a normalization step is usually performed. Gene-expression prognostic classifiers are usually built by correlating gene-expression patterns, generated from tumour surgical specimens, with clinical outcome (development of distant metastases during follow-up) (a). Gene-expression predictive classifiers of response to treatment are generated by correlating gene-expression data, derived from biopsies taken before pre-operative systemic therapy, with clinical and/or pathological response to the given treatment (b). Nature Reviews Cancer 7, 545-553 (July 2007)

Vers une médecine personnalisée FIGURE 2 | Comprehensive clinical decision-making algorithm. From the following article: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Christos Sotiriou & Martine J. Piccart Nature Reviews Cancer 7, 545-553 (July 2007) The ultimate goal will be to integrate several potential clinically relevant parameters into a comprehensive clinical decision-making algorithm that will lead us towards individualized medicine. This algorithm should include traditional clinico-pathological parameters that survive multivariate analysis and incorporate data generated by using the new molecular tools. It must integrate what genomics, genetics and proteomics tell us not only about the tumour but also about the host, and include better information about tumour staging, including the assessment of circulating tumour cells and modern molecular imaging. Nature Reviews Cancer 7, 545-553 (July 2007)

L’institut du thorax L’institut du thorax : CJF 96 01 UMR533 1996 1998 2000 2002 2004 2017 Pole TCV PE CHU Nantes L’institut du thorax : triple tutelle : INSERM, Université, CHU triple mission: enseignement, recherche, soins directoire, conseil de gestion, conseil du personnel, conseil scientifique

Les objectifs de l’institut « Le patient est au centre de l’activité de l’Institut » Soins Recherche Patient Formation Fusion recherche-enseignement-soins Développement de la recherche translationnelle

Activités de soins, d’enseignement et de recherche Chirurgie cardiaque Chirurgie vasculaire Cardiologie Hémodyna-mique Pneumologie Endocrino U1087 CIC Activités de soins, d’enseignement et de recherche

ORGANISATION EQUIPES CLINIQUES EQUIPES DE RECHERCHE Accueil des internes, interfaces Double formation MD/PhD EQUIPES CLINIQUES 7 équipes, du fondamental au pré-clinique Plateformes technologiques EQUIPES DE RECHERCHE INTEGRATION RECHERCHE/CLINIQUE Centre d’Investigation Clinique

L’institut et son environnement pôle de compétitivité génopôle Ouest SFR CIC4 institut du thorax Réseau génétique CV grand ouest Réseau Leducq

la dimension architecturale L’institut du thorax la dimension architecturale Aujourd’hui deux sites éloignés de 10 km

la dimension architecturale L’institut du thorax la dimension architecturale Demain : un institut dans ses murs sur l’Ile de Nantes Projet Ile de Nantes : 70 000 m2 de soin et de recherche

la dimension architecturale L’institut du thorax la dimension architecturale Demain : un institut dans ses murs sur l’Ile de Nantes