(June 16, 2014) Centre d Etudes des Maladies Infectieuses et Pharmacologie Anti Infectieuse (BSL3 facility)

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1 Welcome to the CEMIPAI World! Centre d Etudes des Maladies Infectieuses et Pharmacologie Anti Infectieuse (BSL3 facility)

2 An integrated project in infectiology High level platforms (BSL3 «CEMIPAI» ; I3 «vectopôle»; A3 animal care facility) 3 complementary platforms for «Montpellier Infectious Diseases» (MID) Financial support: CPER «CEMIPAI» platform (BSL3; 550 m2 laboratory) «Vectopole» platform ( I3 insect facilities) «RAM» platform (A2 and A3 animal facilities) N- term 3D8 Screening of antibiotics Vector borne pathogens and Montpellier CNRS/Inserm/ antiviral molecules. IRD, universities 15F8 -BSL2, 10x BSL3 1G5 1B2 - Insect facility I3 (to be built on 23A5 the IRD agropolis site; available in 2014) 13B5 C- term Animal models for infectious diseases

3 Institutional support from the French Ministry of Research Ministère de l Enseignement Supérieur et de la Recherche, Direction Générale de la Recherche et de l Innovation Gilles Bloch Ronan Stephan Roger Genet

4 Institutional support from the LR Region Georges Frêche Christian Bourquin

5 Institutional support from the CNRS and INSERM (ITMO IMMI)

6 Institutional support from the Universities

7 Institutional support «Pôle de Compétitivité» (ORPHEME/EuroBioMed) and associated private companies We have received an institutional support from the «Pôle de compétitivité» EuroBioMed and associated private companies,, for the CEMIPAI project

8 R&D at CPBS: Nosopharm and Deinolab, two examples of academic (CPBS) private partnership a bridge for CEMIPAI A start up from CPBS A public private partnership Philippe Pouletty Président CA Deinove Philippe Villain Guillot, Président Maxime Gualtieri, Dir. Scientifique

9 Competitive statuts:thematic Network for Research and Healthcare (RTRS; IHU) EuroBioMed Consortium (private/public cross fertilization consortium) BCI PHARMA Oxeltis Deinobiotics

10 The CEMIPAI PLATFORM The major aim of the CEMIPAI is to provide tools with high scientific added-value for the academic community and industrial actors of medicine, to validate new therapeutic targets and select new leads. -Bacteriological and virological expertise Search for compounds active on pathogens Characterization of new emerging pathogens -BSL3 pathogen samples preparation for imaging and electron microscopy -Bioinformatic expertise Genetic evolution of pathogens Identification of sequences of interest -Staff training and accreditation for BSL3 Training sessions (CNRS Formation-entreprises) -Supply of BSL3 facility and scientific equipments for academic research teams and private companies CPBS CPBS CPBS CEMIPAI

11 BSL3 CEMIPAI SAS 1 : +15 Pa SAS 2 : - 15 Pa L3 circulation : - 25 Pa L3 modules : - 40 Pa L3 + : - 50Pa V ++ L 11 V ++ Virologie L 06 Criblage L 02 Cytométie L 10 L 09 L 08 L 07 B ++ Vidéo microscopie L 13 Virologie Extétieurs Bactériologie Extétieurs L 15 L 14 L 05L 04 Autoclaves L 03 L B L 01 Bactériologie AERES, January 2014

12 CEMIPAI : bacteriological and virological expertise Virological and bacteriological analytical techniques for screening of compounds active on pathogens (new targets; new leads; e.g. preliminary screening for anti- HTLV compounds in collaboration with Splicos) Characterization of new emerging pathogens (ongoing collaborations with CHU, EFS, Pasteur Institute of Cambodia) Detailed study of the mechanism of action of antiviral compounds (e.g. academic collaboration with chemists at IBMM) High performance screening of anti-infectious molecules (50000 molecules/month; screening capacities availble mid-2014) Robot Zephyr SPE de CALIPER

13 CEMIPAI : BSL3; Pathogen samples preparation; Photonic imaging; Flow cytometry; Dynamic imaging; Electron microscopy Morphological analyses of viruses, bacteria, organelles (resolution 0,4 nm) Immunolocalization of several epitopes specific of the pathogens Negative staining on ultrathin slices Samples observation at the Montpellier CRIC facility 60 nm n m 3 4 The CEMIPAI videomicroscope will be equipped with an incubation device allowing long term cell imaging experiments to test bacteria and viral cell infectivity. Multiple excitation and emission will allow simultaneous multicolour imaging at a single molecule sensitivity levelusing an EM-CCD camera. This equipment will be suitable for TIRF and PALM experiments 6 0 n m : Bourgeonnement de VIH-1 à la membrane plasmique d un lymphocyte 2 : Coupes ultrafines de bactéries Gram négatif 3 : Immunomarquage anti p6, sur VIH- 1 4 : Virus Chikungunya à la surface de cellules HEK293T 5 : Capside isolée du VIH-1 après coloration négative 6 : Exocytose de BSA couplée à de l or colloïdal 7 : Mise à l échelle d une grille portant des coupes d Epon par rapport à une pièce de un centime (Gay &.Briant CPBS)

14 CEMIPAI : bioinformatic expertise Genetic evolution of pathogens Functional annotation of genomic data :DNA sequence annotation; Protein description; NGS data analysis; bioinformatic network integration; phylogenetic analysis (e.g. first annotated sequence of the parasite Babesia microti) Static and dynamic modeling of infectious diseases:evaluation of genetic diversity; phylogeography; multiple timescale modeling; standards and models for data integration (e.g; Dengue virus epidemic in Indonesia; Seasonal epidemic of H1N1 in Thailand; Molecular epidemiology of H5N1 in Cambodia; Molecular epidemiology of RSV, HRV and Chikungunya virus in South-Est Asia; HFMD in Vietnam; Molecular biology and typing of scrub typhus in South Est Asia) Identification of molecular targets : genetic markers identification; diagnostic target; drug resistance and susceptibility (e.g; Artemisin resitance of Plasmodium falciparum in Cambodia) Molecular data integration (polymorphism characterization; multiple sequence comparison; modeling; integration to clinical and epidemiological data (e.g; Dengue virus diversity in South-Est Asia; Modeling of knowledge transfer and translation in public health in Cambodia ) Quality control at genetic level (e.g; Design of new DNA primers) Management of genetic informations

15 CEMIPAI : staff training (accreditation BSL3) Supply of BSL3 facility CEMIPAI is a BSL3 facility classified ZRR «Zone à régime restrictif» and registered for manipulation of «MOT» pathogens (pathogens at risk for bioterrorism). -Staff training and accreditation for BSL3 Training sessions (CNRS Formation-entreprises) -CEMIPAI is a member of the Biosafety and Biosecurity national working group of SFM («Société Française de Microbiologie) on BSL3 and BSL4 laboratories -Supply of BSL3 facility and scientific equipments for academic research teams and private companies

16 January 2015: One of the leader research centers in France dedicated to Infectious diseases «Stratégie Projet CPBS» Basic research in infectiology Clinical investigations Teaching on Infectious diseases Antibiotics and antiviral Drug screening

17 I sincerely wish to thank all those who have contributed to the success story of the CEMIPAI project.. A special thank to: Jean Claude Rossi The next step: Back to science Thank you for your attention!