Annuaire de Projets R&D CLARA - LYONBIOPOLE 2013

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Annuaire des projets R&D financés par le CLARA et LYONBIOPOLE
Comprend les projets Preuve du Concept CLARA, FUI, PSPC et ANR

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Annuaire de Projets R&D CLARA - LYONBIOPOLE 2013

  1. 1. R&D Projects Directory 2 0 1 3
  2. 2. in vitro diagnostics medical technologie > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > Animal medecines FUI AAP12.............................................. ISI Oséo.................................................. FUI AAP14.............................................. ANR 2010..................................................... ANR 2011............................................... Proof of Concept CLARA..................... . ANR 2011............................................... Europe FP7............................................ ANR 2010............................................... FUI AAP15.............................................. ANR 2011............................................... ANR 2008............................................... ANR 2011............................................... ANR 2011............................................... FUI AAP14.............................................. FUI AAP11.............................................. Proof of Concept CLARA..................... . FUI AAP11.............................................. Proof of Concept CLARA..................... . ANR 2011............................................... FUI AAP10.............................................. ISI Oséo.................................................. ISI Oséo.................................................. FUI AAP10.............................................. ANR 2010............................................... ANR 2010............................................... FUI AAP13.............................................. ANR 2012............................................... ANR 2010............................................... Proof of Concept CLARA..................... . Proof of Concept CLARA..................... . ANR 2010............................................... FUI AAP15.............................................. Proof of Concept CLARA..................... . FUI AAP15.............................................. FUI AAP12.............................................. PSPC AAP1............................................ ANR 2011............................................... Proof of Concept CLARA..................... . human medecines 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 ongoing projects ONGOING PROJECTS ACILIMAB ADNA ANTI-PYO APIMIR ARENABUNYAL ARTIS BBMUT BELLEROPHON BHI-PRO BIOFILM CELLESTIM CHEMISPIKE CLARENCE COMBITOX COVALEPT DDELPHES DELICHIUS DIVRESCUE Doc Calipso DORGAN EMER-FAB EMER-IT ETICS FEMTOKINE FLUMA FLUNUCLEOVIR FLUOROMIS II GD-LUNG GEMCO GeniusVac-Mel4 HEPATOFLUO HIFI-ASSAYS HIFI-CAP HIFU HUMAXIS IDITOP IMODI IMOXY LIMLEAD
  3. 3. ACILIMAB in vitro diagnostics 4 LYONBIOPOLE medical technologie > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > Animal medecines Proof of Concept CLARA..................... . ANR 2010......................................... ANR 2010......................................... ANR 2011......................................... ANR 2010......................................... ANR 2012......................................... FUI AAP15........................................ Proof of Concept CLARA..................... . ANR 2012......................................... ANR 2009......................................... ANR 2011......................................... Proof of Concept CLARA..................... . FUI AAP10........................................ ANR 2012......................................... ANR 2009......................................... ANR 2012......................................... ANR 2010......................................... ANR 2011......................................... ANR 2011......................................... ANR 2010......................................... ANR 2012......................................... ANR 2011......................................... FUI AAP9.......................................... ANR 2012......................................... FUI AAP14........................................ ANR 2011......................................... ANR 2010......................................... ANR 2011......................................... Proof of Concept CLARA..................... . ANR 2012......................................... Europe - FP7................................... ISI Oséo............................................ Proof of Concept CLARA..................... . ANR 2010......................................... ANR 2011......................................... ANR 2012......................................... Proof of Concept CLARA..................... . ANR 2011......................................... ANR 2012......................................... human medecines 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 Year Start: 2011 Call for projects: FUI (FUI AAP12) Global budget: 2 820 k€ Public funding: 1 447 k€ Duration: 36 months Stage of development at the beginning of the project: Discovery Accredited by: Lyonbiopole Abstract Chemotherapies can be made more efficient and better tolerated when the active substances are concentrated and targeted to the tumours. Through ACILIMAB a new combined therapy will be developed which will combine active drug-substances, monoclonal antibodies as targeting agents, and Lipidots® as vectors. This delivery strategy will be evaluated on mantle lymphoma cells which are resistant to conventional chemotherapeutics. The aim will be to demonstrate the therapeutic efficacy of drug-loaded immuno-particles, so as to establish therapeutic alternatives for currently non-curable lymphoma. Strategic business area PARTNERS Partners > DD biotech (Company) i YNBIOSE (Company) C OXCAN (Company) V EA LETI (Research Unit) C nticorps anticancer (Research team) A MMUNOLOGIE ANALYTIQUE DES I PATHOLOGIES CHRONIQUES U823 (Research team) Public funders onseil général du Rhône C EDER Rhône-Alpes F onds Unique Interministériel (FUI) – F DGCIS/Oséo rand Lyon G Région Rhône-Alpes Project leader VERMOT-DESROCHES Claudine Entity: iDD biotech Position: RD Director Address: 27, chemin des Peupliers 69570 Dardilly Email: c.vermotdesroches@idd-biotech.com Phone: +33 (0)4 72 52 30 88 Objectives The objectives of ACILILAB project are: • o develop a safe, easy and innovative targeted delivery of high potent therapeutic drug T based on anti CD19 MAb decorated Lipidots® • o demonstrate that MAb-targeted nanoparticles are potentially useful as targeting T delivery systems for chemotherapeutic agents • o acquire knowledge on immuno-nanocarriers as targeted delivery for tumour cells T • o strengthen the therapeutic arsenal for patients clinicians T Innovative assets Application fields Autoimmune diseases / Neurology / Oncology Technological approaches / Keywords Biologics / Drug delivery system / Immunotherapy / Innovative formulation / Nanobiotechnology Through ACILIMAB new platforms were generated dedicated to the development and characterization of drug-loaded immunoparticles. Up to date active drug-substances were screened and selected regarding key parameters such as activity and loading. Futher experiments are in progress to optimize the generation, the stability, the specific cellular binding and internalisation of drug-loaded immuno-particles. Actual Outcomes Perspectives The main outcomes of ACILIMAB will to combine active drug-substances, monoclonal antibodies as targeting agents, and Lipidots® as vectors to manage the balance of beneficits and risks of chemotherapies. Mantle lymphoma © ACILIMAB Search of partnership Search for technologies Preclinical assay realization Search for private financing Search for public funding Proof of concept LYONBIOPOLE 5 ongoing projects ongoing projects LIPOBACK MELASCAN MIT-2M MRSA-VAC MULTICELLS MULTIMAGE MUTATION NanoEno NANOLUPUS NIVPATH NOBLEACH ONCOFLUO OPTIMABS OREGA-17 PA-ANTIADH PA-CONTROL PECSDELI PHOTO-SRM PILIPATH PLASMOSC PLATISSEP PLUS POLYBIO PREDIVAC PREMAG QUINOLAC SECPATH STING 2.0 SYNFRIZZ SYNODOS SYSCLAD TEDAC THERA8 TOLLREG TOXOCAG TULAREDRUG UROLINK VICIT VIVABRAIN Resistance treatment and optimization of cancer treatment by vectorisation of immune targeted active drug-substances
  4. 4. ADNA NEW Advanced Diagnostics and New therapeutic Approaches ongoing projects Abstract The ADNA program seeks to develop a more personalized form of medicine, focusing on infectious diseases, cancers and rare genetic diseases by providing innovative «theranostic» products and services for healthcare professionals. The program intends to identify, validate biomarkers for providing diagnostic and therapeutic solution to healthcare needs which are not currently addressed efficiently. PARTNERS Partners INSTITUT MERIEUX (Company) bioMérieux (Company) CEA LETI (Company) Transgene SA (Company) ST Microelectronics (Company) Genethon (Research unit) enosafe (Company) G ospices Civils de Lyon (Healthcare H unit) niversité Claude Bernard Lyon 1 U (Research unit) Public funders séo / BPI France O Design, synthesis and pharmaceutical development of antiadhesion glycoclusters inhibitors of infection by Pseudomonas aeruginosa Project leader GUILLEN Christine Entity: Institut Mérieux Position: Program Director Address: 17, rue Bourgelat 69002 LYON Email: christine.guillen@institut-merieux.com Phone: +33 (0)4 78 87 70 72 Objectives Based on the observation that specific genetic factors determine how each individual patient responds to treatment, the objective is to develop products that can be used to better diagnose diseases or predict patient response, so that a tailored treatment program can be devised, providing better care to patients. Innovative assets ADNA program combines innovative assets for each partner: Strategic business area Application fields Genetic / Rare diseases / Infectious diseases / Inflammatory diseases / Oncology Technological approaches / Keywords Bioinformatics / Software / Biomanufacturing / Immunotherapy / Innovative formulation / Vector vaccine • Genethon will test on patients the first therapy genetic treatment produced in “Géné thon bioProd”, the largest bioproduction facility in Europe (this site is not part of the ADNA program and was not granted by OSEO/BPI). • Transgene aims, with TG4010, to propose a therapeutic vaccine associated with two companion tests, combining immunology and cell sorting technologies. Year Start: 2012 Call for projects: FUI (FUI AAP14) Global budget: 6 332 k€ Public funding: 1 980 k€ Duration: 36 months Stage of development at the beginning of the project: Discovery Accredited by: Lyonbiopole Co-accredited by: Eurobiomed Abstract The use of multivalent high affinity glycoclusters is a promising approach for the treatment of lung infections associated with Pseudomonas aeruginosa. These patented molecules target bacteria key virulence factors such as lectins PA-IL and PA-IIL, involved in adhesion to lung cell surface and biofilm formation. ANTI-PYO activities are the evaluation and the improvement of the anti-bacterial activity of these molecules, the industrial manufacturing of the best molecules and the beginning of their development in order to identify one candidate for pharmaceutical development. Strategic business area Application fields Infectious diseases Technological approaches / Keywords Biomanufacturing / Functional Screening / Drug discovery / Nanobiotechnology • BioMerieux innovates in bioMarkers field, especially in sepsis and liver cancer, associated with new technologies as Mass spectrometry or New generation sequencing. All partners included: 49 publications, 80 posters or communications, 31 patents Transgene: Development of therapeutic vaccine for Non-Small Cells Lung Cancers: End of Phase IIb/III planned for 2013. Development of therapeutic vaccine for Head Neck cancers in collaboration with EORTC started in 2013 Genethon: Development of genetic the6 LYONBIOPOLE rapy for Duchene Muscular Dystrophy. Begin of Clinical trials in 2014. BioMerieux: 2 new biomarkers (for sepsis and liver cancer) on test phases. Innovative diagnostic systems (for immunology and molecular biology applications) under development. 1 Product, prototype, service 10 Proof of concepts Preclinical assay 3 Clinical trials 31 Patents 49 Scientific publications 80 Communications in international congresses 6 PhD 186 Sustainable Job creations at the end of the project 45 Job creations in Rhône-Alpes region Partners licityl (Company) E anofi RD (Company) S entre de recherches sur les C macromolécules végétales (Cermav) UPR5301 (Research unit) nstitut de Chimie et Biochimie I Moléculaires et Supramoléculaires (ICBMS) - UMR5246 (UCBL-CNRS) (Research unit) aboratoire d’Ingénierie des L Systèmes Macromoléculaires (LISM) UMR7255 (Research unit) niversité de Lille II (Research unit) U Public funders onds Unique Interministériel (FUI) – F DGCIS/Oséo Région Rhône-Alpes onseil général des Bouches-duC Rhône Project leader DARBLADE Benoît Entity: Elicityl Position: Healthcare program manager Address: 746, avenue Ambroise Croizat 38920 Crolles Email: benoit.darblade@elicityl.fr Phone: +33 (0)4 76 40 71 61 Objectives The objective is to develop a drug candidate to treat lung infections related to Pseudomonas aeruginosa in patients in intensive care and in patients with cystic fibrosis. This bacteria is the leading cause of infection in patients in intensive care and is responsible for 80% of mortality in patients with cystic fibrosis. The molecules developed in ANTI-PYO will have to prevent bacterial attachment to the lung surface, to facilitate their elimination by the immune system and to make them much more sensitive to standard antibiotic’s treatments against which the bacteria has become resistant. Innovative assets ANTI-PYO exploits the potential of natural carbohydrates and glycocluster technology for the development of a new generation of molecules active against bacterial infection. The originality of the program comes from • he use of bacterial fermentation for the T production of the carbohydrate moieties of the glycoclusters and • he versatile architecture of the glycoT clusters to converge to the best avidity toward bacterial molecular targets. ANTI-PYO proposes promising anti-bacterial approach aiming at inhibiting key virulence factors involved in bacteria adhesion and biofilm formation. Advanced Diagnostics for New therapeutic Approaches Actual Outcomes PARTNERS Actual Outcomes Perspectives Job creation in Rhône-Alpes region Increase in turnover Pseudomonas aeruginosa lectin PA-IL © A Imberty - CNRS Preclinical assay realization Clinical trial realization LYONBIOPOLE 7 ongoing projects Year Start: 2007 Call for projects: ISI Oséo Global budget: 202 263 k€ Public funding: 89 514 k€ Duration: 120 months Stage of development at the beginning of the project: Basic research / Discovery / Preclinical development Accredited by: Lyonbiopole www.institut-merieux.com/projetssante_adna.php ANTI-PYO
  5. 5. APIMIR ARENABUNYAL Year Start: 2011 Call for projects: ANR (ANR2010 - BLANC) Global budget: 600 k€ Public funding: 600 k€ Duration: 48 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole PARTNERS Partners Laboratory Adaptation and Pathogenicity of Microorganisms UMR 5163 (Research unit) Institut Pasteur (Research unit) Large Scale Biology (BGE) - U 1038 (Research unit) Public funders NR, Agence Nationale de la A Recherche ongoing projects Abstract This proposal focuses on the basis of host cell manipulation by Plasmodium and Toxoplasma, the agents of malaria and toxoplasmosis, respectively. MicroRNAs are a class of small noncoding RNAs that modulate the gene function at the post-transcriptional level and act as a fine tuner of various biological processes, such as development or immunity. Inspired by the work on viruses and bacteria, we recently started to explore whether Plasmodium and Toxoplasma co-opt, impinge on, or subvert microRNA-directed functions as a means to alter gene expression in host human cells. Strategic business area Project leader HAKIMI Mohamed-Ali Entity: CNRS Position: Research Professor Address: UMR5163, Domaine de la Merci 38700 GRENOBLE Email: Mohamed-ali.hakimi@ujf-grenoble.fr Phone: +33 (0)6 77 43 79 54 Objectives To examin the human small microRNome patterns following T. gondii and P. berghei infection. To select pertinent microRNAs and experimental validation of their target (genes) pathways. • For those that have all the attributes, we will investigate more deeply how they contri bute in host cell to promote or prevent parasite infection by using microRNA depletion and overexpression. • To identify parasite effector molecules (small RNAs or proteins) that hijack the RNA silencing machinery in the host cell. Innovative assets Structural, mechanistic and inhibitor design studies of the Bunya - and Arenavirus L-proteins Year Start: 2011 Call for projects: ANR (ANR2011 - BLANC) Global budget: 2 204 k€ Public funding: 350 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Abstract The ARENABUNYA-L project aims to derive a structure-based, mechanistic model to explain how arena- and bunyavirus RNA polymerases function in both transcription and replication of the viral genome. Transcription in these viruses is performed by ‘cap-snatching’ but this occurs in the cytoplasm, whereas influenza virus does this in the nucleus. Structural information on cap-snatching will be used to optimise inhibitors as a first step towards antiviral drug design. Strategic business area The microRNA matured in multiple steps in the cells is taken into the RNA-induced silencing complex (RISC) to regulate mRNA expression and stability. Recent data point to the possibility that apicomplexans alter the host microRNome, thereby identifying the RNA silencing pathway as a new means by which they reshape their cellular environment. We identified a large number of host genetic riboregulators whose expression was tightly regulated 8 LYONBIOPOLE by Toxoplasma infection. We also report that two immunomodulatory microRNAs contribute to better control of parasite burden in the brain and promoted resistance to Toxoplasma infection. Scientific publications 2 Partners aboratoire Architecture et Fonction L des Macromolécules Biologiques (AFMB) (Research unit) uropean Molecular Biology E Laboratory (EMBL) (Research unit) Public funders NR, Agence Nationale de la A Recherche Project leader CUSACK Stephen Entity: European Molecular Biology Laboratory Position: Head of Outstation Address: 6, rue Jules Horowitz 38042 Grenoble Email: cusack@embl.fr Phone: +33 (0)4 76 20 72 38 Objectives The overall goal of this project is to derive a structure-based, mechanistic model to explain how segmented, negative-strand RNA viral polymerases function in both transcription and replication. Innovative assets We will use recombinant arena- and bunyavirus RNA polymerases and complexes with viral RNA to study in vitro polymerase mechanisms by biochemical and structural biology methods. Application fields Infectious diseases Technological approaches / Keywords Structural Biology Toxoplasma and Plasmodium subversion of host cell miRNAs for parasite intracellular development Application fields Infectious diseases Technological approaches / Keywords Genetics / Genomics Actual Outcomes PARTNERS Schematic diagram of the architecture of cap-snatching, segmented negative strand RNA viral polymerases. The polymerases of different genera are represented as lines with the size in amino acid residues of the representative species shown. The blue box at the left indicates the endonuclease domain with the particular sequence signature of that genus written above. The central box represents the conserved polymerase domain. In the case of orthomyxoviruses (e.g. influenza), the three subunits PA, PB1 and PB2 of the heterotrimeric polymerase are represented co-linearly with the total number of residues shown. The blue box in influenza PB2 represents the cap-binding domain, which is possibly located in the C-terminal region of the other L-proteins (question mark). Perspectives Set-up of a new RD project Clinical trial realization Actual Outcomes We have determined the crystal structure of the nucleoprotein of La Crosse orthobunyavirus in complex with single- stranded RNA and proposed a model of how it packages the RNA genome. Scientific publication 1 LYONBIOPOLE 9 ongoing projects Toxoplasma and Plasmodium subversion of host cell miRNAs for parasite intracellular development
  6. 6. BBMUT NEW Artificial testis for fertility preservation of children with cancer Year Start: 2013 Call for projects: Proof of concept CLARA Global budget: 1 250 k€ Public funding: 355 k€ Duration: 36 months Stage of development at the beginning of the project: Preclinical development ongoing projects Abstract While sperm cryopreservation before starting oncological treatment is efficient for fertility preservation in adult males, in prepubertal children only spermatogonia are available from testicular tissue, and no system of maturation are currenty available. The company Kallistem and academic partners (Université Claude Bernard Lyon 1, Hospices Civils de Lyon, INSERM, CNRS, INRA) developped a prototype of «artificial testis» to perform ex vivo spermatogenesis from immature testicular tissue. The financial support of CLARA will be determinant to transfer this method from rat to humans. PARTNERS Partners Hospices Civils de Lyon (Healthcare unit) Kallistem (Company) Inserm U846 (SBRI) (Research unit) UMR CNRS 5223 (IMP) (Research unit) Public funders onseil général de Rhône C rand Lyon G Project leader LEJEUNE Hervé Entity: Centre Hospitalier Universitaire de Lyon Position: Professor of Endocrinology Address: Hôpital Femme Mère Enfant 59, bd Pinel - 69500 Lyon Email: herve.lejeune@chu-lyon.fr Phone: +33 (0)4 72 12 97 92 Objectives One child out of 500 is affected by cancer. More than 75% of them will be cured. Hence, 1/1000 young adult (20-30 y.o.) is a cancer survivor. These therapies are known for their gametotoxic effects that can cause sterility. The aim of the ARTIS project is to develop a system to produce mature sperm cells ex-vivo, from germline stem cells contained in immature testicular tissue. This includes preclinical studies in the rat for safety issues. The final objective is to preserve fertility of prepubertal boys before oncological treatment known to induce sterility by spermatogenic failure. Innovative assets Strategic business area Application fields Oncology Technological approaches / Keywords Cell model / Animal model / Cell therapy / Regenerative Medicine The whole ARTIS project is innovative. To our knowledge no “artificial testis” are currently available. The main steps of the project are: • Production of sperm cells in sufficient amount to perform ICSI, • Study the quality of ex-vivo produced sperm cells in rat, • tudy the quality of conceptus in the rat (anatomo-physiological and comportmental S studies), • Transfer to human testicular tissues and study the quality of ex-vivo produced human sperms and finally, • Determine the practical and ethical conditions for a clinical trial in prepubertal boys. Actual Outcomes Perspectives In vitro spermatogenesis was studied in our group from 1997 (Weiss et al. Biol Reprod. 1997;57:68-76). In 1999 we published that one application of in vitro spermatogenesis will be to preserve fertility in prepubertal boys before oncological treatment (Lejeune H, Durand P. Conservation de tissu testiculaire et maturation in vitro de la lignée germinale pour préservation du potentiel de reproduction avant traitement anticancéreux chez le garçon pré-pubère. Andrologie, 1999;9:498-504.) The system is now advanced enough to propose the development of this project for a clinical application. Clinical trial realization Proof of concept Patents 10 LYONBIOPOLE testimony Pr. Hervé Lejeune, clinician pratician at Hôpital Femme Mère Enfant The genesis of the project goes back to the publication in 1999 of joint results with Philippe Durand on the conservation of testicular tissue and the in vitro maturation of the germ line. The idea of ARTIS took place during the 2010 Industrial-Academic Meetings of CLARA, when Laurent David’s team presented its work on the application of biopolymers in cell culture. Experiments are conducted and the project becomes credible when the last steps of the in vitro spermatogenesis are conducted. The par- Broad Band ultrasound imaging using CMUT Year Start: 2012 Call for projects: ANR (ANR2011 - TECSAN) Global budget: 2 032 k€ Public funding: 782 k€ Duration: 42 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Abstract The early diagnosis of liver diseases and/or identification of any focal lesions are key issues to consider a favorable prognosis. These objectives require non-invasive dedicated diagnostic tools and justify the development of innovative techniques. The BBMUT project aims to exploit the properties of a promising new technology of ultrasound probes, called CMUT, to propose new techniques for imaging and characterization of liver tissue. The CMUT probe, developped by the company Vermon, is characterized by a large frequency band. The harmonic imaging techniques will be especially investigated. Strategic business area Application fields Oncology Technological approaches / Keywords Imaging (medical) / Ultrasound PARTNERS Partners REATIS (Research unit) C ospices Civils de Lyon (Healthcare H unit) ermon (Company) V MR930 «Imagerie et Cerveau» U (INSERM) (Research unit) aboratoire de Mécanique et L d’Acoustique (LMA) - UPR 7051 (Research unit) Public funders NR, Agence Nationale de la A Recherche Entity: CREATIS Position: Professor Address: 7, av. J. Capelle 69621 Villeurbanne Email: olivier.basset@creatis.univ-lyon1.fr Phone: +33 (0)4 72 43 85 69 Objectives • esign of a CMUT probe whose specifications are adapted to the examination of the D liver Implementation of innovative techniques based on Chirp or composite signal emission. • upply of a native image that has improved contrast without degrading the resolution. S • evelopment of an ultrasonic method for characterizing tissue structures adapted to D liver. • uantitative measurement of the nonlinearity parameter. Q • re-clinical validation to quantify the diagnostic relevance of the proposed approaches. P Innovative assets The innovative aspects of the project consists in the development of specific imaging technique for image improvement or tissue characterisation dedicated to the large bandwidth of cmut probe. Cmut probe and ultrasound image of a circulating contrast agent using a harmonic imaging technique tnership with academic and clinical actors materializes when the company Kallistem is created in 2012. To us, CLARA promotes the synergy between partners involved in the project. Through its selection in the CLARA Proof of Concept program, and its financing by territorial collectivities, the support of ARTIS corresponds to one the 2009-2013 Cancer Plan which focuses on improving access to the preservation of fertility in cancer patients. The specificity of the Proof of Concept programs allows us to be accompanied by CLARA on the regulatory aspects and in our approach to Health authorities. Project leader BASSET Olivier Actual outcomes 3 Scientific publications 4 Communications in international congresses Perspectives Preclinical assay realization LYONBIOPOLE 11 ongoing projects ARTIS
  7. 7. BHI-PRO NEW Combining cellular and humoral immune responses as a vaccine strategy against staphylococcus aureus Year Start: 2013 Call for projects: European funding (FP7 - Health) Global budget: 7 000 k€ Public funding: 5 500 k€ Duration: 36 months Stage of development at the beginning of the project: Preclinical development Accredited by: Lyonbiopole Project supported by Lyonbiopôle only PARTNERS Partners Jenner Institute at Oxford University (Research unit) European Vaccine Initiative (Other) Preclin Biosystems (Research unit) Public funders European Commission ongoing projects Abstract S. aureus is one of the most important bacterial pathogens of man. Morbidity and mortality are associated with invasion of tissues and abscess formation. EU costs from these infections are estimated at EUR 380 million per annum. Since there is no vaccine approved by major regulatory agencies, and since recent clinical trials have proven unsuccessful, prevention, like treatment, remains dependent on antimicrobials. But resistance is increasing, so the utility of this option will decrease in the short to medium term. Strategic business area Project leader LE VERT Alexandre Entity: IMAXIO Position: Directeur Général Address: 99, rue de Gerland 69007 LYON Email: alevert@imaxio.com Phone: +33 (0)6 79 82 92 70 Objectives The objective of this project is to create an entirely novel vaccine against Staphylococcus aureus infection in man. The concept described here is to target both cellular and humoral immune responses using a vaccine to be designed, manufactured, and assessed in terms of safety and immunogenicity in man as part of this grant. The novel vaccine generated will be applicable to both beta-lactam resistant and sensitive S. aureus (MRSA MSSA) strains. Innovative assets The consortium will use three building blocks to design the vaccine: • A newly discovered, highly conserved T-cell inducing antigen • A commonly expressed, conserved antigen neutralised by antibodies (Hla) • An innovative, proprietary and potent pro-immunogenic tag (IMX313) which can be fused to the antigens. Application fields Infectious diseases Technological approaches / Keywords Immunotherapy / Vector vaccine Bayesian hierarchical inversion for mass spectrometry. Application to discovery and validation of new protein biomarkers Year Start: 2011 Call for projects: ANR (ANR2010 - BLANC) Global budget: 1 824 k€ Public funding: 838 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research, Clinical trials Accredited by: Lyonbiopole Abstract To control the technological variability on MS-based analytical chains for clinical proteomic studies, we propose to introduce a relevant hierarchical modeling of the MALDI and SRM chains within a Bayesian statistical framework. The new Bayesian Hierarchical Inversion algorithms will rely on the stochastic sampling inverse problem methodology. For biostatistics, we propose to evaluate the sensitivity, specificity of sample classification and the statistical power of biomarker selection. Evaluation will be carried on synthetic and patient samples within oncology and colorectal cancer studies. Strategic business area Application fields Health Environment / Oncology Technological approaches / Keywords Bioinformatics / Software / Omics Technologies / Biomolecular devices / Mass spectrometry / Signal processing Actual Outcomes Staphylococcus aureus Actual Outcomes The FP7 grant will be used to complete pre-clinical tests as well as a Phase I clinical trial in humans in 2016 for the development of a vaccine indicated in Staphylococcus aureus infections. 12 LYONBIOPOLE Proof of concept Preclinical assay Clinical trials Scientific publications Perspectives Clinical trial realization Main deliverables: • Oncological data sets from synthetic and patient sample cohorts delivered by CLIPP on MALDI platform in discovery mode, • Colorectal cancer data sets from synthetic and patient sample cohorts delivered by bioMérieux on SRM/MRM3 platform in validation mode, • A Bayesian Hierarchical Inversion software dedicated to the MALDI platform in discovery mode, • A Bayesian Hierarchical Inversion software dedicated to SRM/MRM3 PARTNERS Partners CEA LETI (Research Unit) bioMérieux (Company) aboratoire de l’Intégration du L Matériau au Système (IMS) - Univ. Bordeaux, UMR 5218 (Research unit) aboratoire « Biométrie et Biologie l Evolutive » UMR 5558 (Research unit) entre Hospitalier - Université de C Dijon (Healthcare unit) Public funders NR, Agence Nationale de la A Recherche Project leader GRANGEAT Pierre Entity: CEA Leti Position: Research director Address: CEA Leti, MINATEC Campus, DTBS, 17, rue des Martyrs 38054 GRENOBLE cedex 9 Email: pierre.grangeat@cea.fr Phone: +33 (0)4 38 78 43 73 Objectives • o increase robustness of discovery and validation studies on a MALDI platform (CLIPP) T and a SRM/ MRM3 platform (bioMérieux) by controlling technological variability • o design a Bayesian framework combining hierarchical mixture models, probability T distributions, and stochastic sampling inversion algorithms • o evaluate the statistical power of discrimination test T • o study synthetic and patient sample cohorts in oncology and colorectal cancer T • o combine in a single research project Bayesian inversion, biostatistics, and proteoT mics platforms Innovative assets The introduction of a new marker using stateof-the-art immunoassays (ELISA) is currently expensive and time-consuming. Also the mass spectrometry technology should shorten the delay and improve the efficiency of protein markers discovery and validation. However, there is a need for automatically operating a mass spectrometry analytical chain and the associated data analysis. The proposed Bayesian Hierarchical Inversion algorithms will improve the measurement reliability and the sensitivity, specificity and statistical power of biomarker discovery and associated clinical diagnostic. platform in validation mode, • A biostatistics guideline report. Products, prototypes, services 2 A bayesian hierarchical inversion software for MRM in validation mode - a bayesian hierarchical inversion software for MALDI in discovery mode Proof of concept 1 A bayesian hierarchical inversion software for MRM in validation mode 3 Clinical trials Colorectal cancer study in MRM mode - Hepato-Cellular Carcinome study in MALDI mode - Steatose study in MALDI mode bioMérieux platform: liquid chromatograph (Dionex, Ultimate 3000) and SRM/MRM3 triple quadrupole mass spectrometer (ABSciex, ABI 5500QT) © bioMérieux 0 Communications in international 1 congresses 1 PhD Perspectives Search of partnership Set-up of a new RD project Preclinical assay realization Clinical trial realization Search for private financing Search for public funding LYONBIOPOLE 13 ongoing projects BELLEROPHON
  8. 8. CELLESTIM NEW Antibiofilmogram® Test PARTNERS ongoing projects Year Start: 2013 Call for projects: FUI (FUI AAP15) Global budget: 4 310 k€ Public funding: 1 285 k€ Duration: 36 months Stage of development at the beginning of the project: Discovery Accredited by: Lyonbiopole Co-accredited by: Alsace BioValley www.antibiofilmogramme.fr Partners BioFilm Control (Company) bioMérieux (Company) Hospices Civils de Lyon (Healthcare unit) CHU Grenoble (Healthcare unit) CHU Strasbourg (Healthcare unit) CHU Clermont-Ferrand (Healthcare unit) CHU Nîmes (Healthcare unit) Public funders Conseil général du Puy de Dôme FEDER Auvergne Fonds Unique Interministériel (FUI) – DGCIS/Oséo Région Auvergne Cellular estimation of immunity Project leader Bernardi Thierry Entity: BioFilm Control Position: CEO Address: Biopôle Clermont Limagne 63360 Saint-Beauzire Email: thierry.bernardi@biofilmcontrol.com Phone: +33 (0)4 73 33 39 80 Abstract Objectives The project is based on the assumption that the development of an in vitro biofilm in the presence of antibiotics is correlated with a decrease in the effectiveness of the antibiotic treatment. This project aims to: • Demonstrate the clinical value of an early detection of the biofilm in response to antibiotic treatment. • Allow a rapid adaptation of the empiri cal treatment administered. • Choose the best antibiotic treatment for chronic infections The Antibiofilmogramme® will be a new tool to fight against multidrug-resistant infections. The project aims to develop a brand new antibiogram test, named Antibiofilmogramme®, that will take into account the «biofilm» behaviour and its medical value to prevent therapeutic failures. The BIOFILM project offers the possibility to the French consortium and in particular to BioFilm Control to compete at the highest level. The recognized experience of the consortium partners on their core activity combined with their critical size is ideal to launch the revolutionary test on the international market and obtain a scientific, industrial and economic success. Strategic business area Application fields Infectious diseases Technological approaches / Keywords Biologics / Diagnosis Innovative assets • Development of a new automated antibiogram test (a rapid test able to detect virulent strains within 6 hours rather than 48h to 72 hours actually) • Provide guidelines and recommen dations regarding the interpretation of in vitro antibiogram test, in the future the biofilm behavior of germs may be taken into account when an antibiotic treatment is prescribed • The RD studies with our clinical partners will provide an RD synergy to discover new ways of treating infections multi-resistant or not. Year Start: 2012 Call for projects: ANR (ANR2011 - P2N) Global budget: 1 461 k€ Public funding: 676 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Co-accredited by: Medicen Paris Region www.inac.cea.fr PARTNERS Partners tructure et Propriétés S d’Architectures Moléculaires (CNRSCEA-UJF) (Research unit) ervice de Chimie Bioorganique et de S Marquage (SCBM) (Research unit) oriba Jobin Yvon (who baught H genOptics) (Company) Public funders NR, Agence Nationale de la A Recherche Abstract We propose a low-cost and low-technology approach to investigate individual cell responses, based on ‘individual cell’ monitoring. This difference is fundamental as the individual cell approach allows the investigation of biological signals at the cellular level, collected from a cell interacting with other cells. A second significant advantage of our approach is the ability to access a statistically relevant number of individual responses. We are confident in the fact that these data should allow us to describe different secreting-ability profiles, depending on physiological states. Strategic business area Application fields Infectious diseases / Inflammatory diseases Technological approaches / Keywords Biochips Project leader ROUPIOZ Yoann Entity: CNRS Position: Research Scientist Address: SPrAM/INAC, CEA-Grenoble 38054 Grenoble Email: yoann.roupioz@cea.fr Phone: +33 (0)4 38 78 98 79 Objectives The targeted objective of our project is the real-time monitoring on a biochip of Influenza-triggered immune response at individual cell levels. The core of our project is the detection of secreted proteins on surface functionalized with specific biomolecules used as secretion-capture elements. An optical monitoring of the interaction will be led using surface plasmon resonance phenomenon, propagating an evanescent wave on a gold surface. Innovative assets This project is focused on the development of original biochips allowing the fast detection of in vitro immune response induced by pathogens. This tool should allow to efficiently and rapidly screen for vaccine candidates but also to identify original pathogens inducing immune responses. Artist view of each element to be integrated in a SPR imager (e) fully compatible with blood cells (a) culture in a thermostatic volume (c) supplemented with CO2 (d). The core of the technology is the biochip sensor (b) based on a glass prism covered with a 50 nm thick gold layer. Such technology should allow the real-time visualization of secreting cells (f). © Yoann ROUPIOZ BioFilm Ringtest © BioFilm Control Actual outcomes 60 to 70% of medical decisions involve the result of in vitro diagnostics. The annual global market for Microbiological Diagnosis represents 7% of the in vitro diagnostics market, which is about 30 billion euros. It is up to 5% per year. 90% of the market is shared equally by 14 LYONBIOPOLE three key players: bioMérieux (Machine VITEK®), Siemens (Microscan) and Becton Dickinson (Phoenix). The BIOFILM project provides a strategic opportunity in the current context because it can modifiy the established balance in favor of French champions such as BioFilm Control and bioMérieux. Perspectives Set-up of a new RD project Search for private financing Actual Outcomes We just reached the mid-project term. Most outcomes are expected to arise during the last phase of the project. But we can already mention the completion of the first SPR imager, dedicated to cell culture on a chip. 1 Prototype Prototype for cellular culture (for 2448h) on a chip allowing SPR imaging. Perspectives Search of partnership Search for clinical samples. LYONBIOPOLE 15 ongoing projects BIOFILM
  9. 9. CHEMISPIKE CLARENCE Inhibition of syndecan-1 mediated cell adhesion ongoing projects Abstract Syndecans are transmembrane heparan sulfate proteoglycans widely expressed in developing and adult tissues. Several studies report involvement of syndecans in human diseases such as cancers and infectious diseases. Among these, a syndecan-1 interaction with laminin 332 was shown to influence epithelial cell behavior and potentially impact carcinoma development. Through a high-throughput screening assay of a large library of chemical agents at the « Plateforme de Criblage de Molécules Bio-Actives », we have identified promising inhibitors of the syndecan-1 mediated cell adhesion pathway. Strategic business area Application fields Infectious diseases / Oncology Technological approaches / Keywords Analytical Chemistry / Chemotherapy / Functional Screening / Drug discovery / Structural Biology PARTNERS Partners Institut de Biologie et Chimie des Protéines (IBCP) - UMR 5305 (CNRSUCBL1) (Research unit) Conception, synthèse et vectorisation de biomolécules - Institut Curie / CNRS UMR 176 (Research unit) IBS - INSTITUT DE BIOLOGIE STRUCTURALE - UMR 5075 (Research unit) Public funders ANR, Agence Nationale de la Recherche Project leader ROUSSELLE Patricia Entity: Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique - Institut de Biologie et Chimie des Protéines - UMR 5305 CNRS UCBL Position: Research Director Address: 7, passage du vercors 69367 Lyon Email: patricia.rousselle@ibcp.fr Phone: +33 (0)4 72 72 26 39 Objectives The proposal CHEMISPIKE aims at: • Dissecting the molecular mechanism underlying the syndecan-1 mediated cell adhe sion cascade, • Identifying, among the hits coming from the screening, specific syndecan-1 inhibitors and determine their intracellular target, • Characterizing/optimizing the selected molecules through medicinal chemistry and test their potential anti-tumoral properties in vitro using colon and breast carcinoma cells • Solving the structure of the laminin 332 domain involved in syndecan-1 interaction using X-ray crystallography. Year Start: 2012 Call for projects: ANR (ANR2011 - P2N) Global budget: 10 k€ Public funding: 520 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Abstract As exposure to environmental carcinogens may increase the risk of sporadic breast cancers, it is important to decipher the role of environmental carcinogens in the chronic carcinogenesis of human breast epithelia and their contribution in the development of this cancer. The CLARENCE project aims to use a tumor progression model of breast cancer that mimics progression from the benign to the premalignant status and from the premalignant to the malignant status to study the impact of chronic and low-dose exposure to two environmental carcinogens. Strategic business area Innovative assets The major innovative asset of Chemispike relies on the fact that syndecan-1 inhibitory molecules were tested in the context of a cell adhesion assay. Molecules were selected upon their potential to inhibit syndecan-1 mediated adhesion to laminin and were shown to operate at the intracellular level most likely targeting the syndecan-1 signaling cascade. In addition to its impact in oncology, this project could have an impact in the treatment of infectious diseases as syndecan-1 is known to be an important receptor/co-receptor involved in some The chemispike project aims at identifying and developing bacterial and viral pathogens, mediating small molecules with potential to inhibit the interaction of the infection. cell adhesion receptor syndecan-1 expressed at the surface of Application fields Health Environment / Oncology Technological approaches / Keywords Biobank / Cell model / Animal model / Minimally Invasive Technologies epithelial cells with proteins of the microenvironment. Actual Outcomes The major innovative asset of Chemispike relies on the fact that syndecan-1 inhibitory molecules were tested in the context of a cell adhesion assay. Molecules were selected upon their potential to inhibit syndecan-1 mediated adhesion to laminin and were shown to operate at the intracellular level most likely targeting the syndecan-1 signaling cascade. 16 LYONBIOPOLE In addition to its impact in oncology, this project could have an impact in the treatment of infectious diseases as syndecan-1 is known to be an important receptor/co-receptor involved in some bacterial and viral pathogens, mediating infection. Scientific publications 8 8 ommunications in international 1 C congresses 2 PhD Perspectives PARTNERS Partners épartement Cancer et D Environnement, Centre Léon Bérard (Research unit) RCL, Inserm U1052-CNRS 5286 C (Research unit) ’Institut de Recherche en L Cancérologie de Montpellier (IRCM U896) (Research unit) aboratoire HydroSciences L Montpellier (UMR5569 CNRS,IRD, UM1, UM2) (Research unit) lateforme de Recherche en P Toxicologie Environnementale et Ecotoxicologie (Research unit) Voir le sitePROFILEXPERT (Company) Public funders NR, Agence Nationale de la A Recherche Project leader COHEN Pascale Entity: Département Cancer et Environnement, Centre Léon Berard Position: Professor Address: 28, rue Laënnec 69373 Lyon Email: pascale.cohen@univ-lyon1.fr Phone: +33 (0)4 78 77 28 94 Objectives • o identify and establish an original in vivo or in vitro biological model that could allow T the study of candidate environmental molecules • o investigate the cellular, molecular, epigenetic, transcriptomic and metabolomic T impacts of chronic and low-dose [B(a)P and/or BPA] exposure in a tumor progression model of breast cancer • o perform in vivo investigation T • o identify putative human candidate biomarkers of BPA and/or B(a)P exposure and T putative molecular targets that could be used by agents to overcome environmental exposure Innovative assets The overall novelty of the research program is the strategy focused on the combination of two environmental molecules possessing two different mechanisms of toxicity and tested in a model of tumor progression in breast cancer. This is in contrast with classical approaches aimed at testing each environmental molecule individually, thus overlooking the potential cross-talk and potentialization between different environmental molecules. Characterization -Optimization Establishment of exposed cell mini-bank Preclinical assay realization Search for private financing Search for public funding Actual outcomes Perspectives 2 Communications in international congresses Scientific publications LYONBIOPOLE 17 ongoing projects Year Start: 2009 Call for projects: ANR (ANR2008 - PCV) Global budget: 2 020 k€ Public funding: 625 k€ Duration: 56 months Stage of development at the beginning of the project: Basic research, Discovery, Accredited by: Lyonbiopole Cellular, molecular and genomic investigation of chronic environmental exposure of low doses pollutants in a tumour progression model of breast cancer
  10. 10. COMBITOX NEW Year Start: 2012 Call for projects: ANR (ANR2011 - ECOTECH) Global budget: 2 969 k€ Public funding: 999 k€ Duration: 36 months Stage of development at the beginning of the project: Prototype Accredited by: Lyonbiopole ongoing projects Abstract The objective of this project is the conception of a multi-parametric instrument for continuous measurement of toxic compounds. Biosensors modules will be developed and optimized starting from technologies developped and transferred to an in-line measurement device. A prototype will be set up in a water pumping station. A marketing enquiry will help us to adapt the performance of the device according to the requirement of water-management professionals. The device will allow the detection of bio-available toxic compounds as well as harmful microorganisms which can impact human health. Strategic business area Other Application fields Health Environment Technological approaches / Keywords Environmental biology PARTNERS Partners CNRS (Research unit) Laboratoire de bioénergétique cellulaire (LBC) (Research unit) CEA Cadarache (Research unit) INSA Lyon (Research unit) Ecole des Mines D’alès (Research unit) ap2e (Company) Public funders ANR, Agence Nationale de la Recherche Project leader PIGNOL David Entity: CEA Cadarache Position: Reseach Director Address: IBEB-LBC-CEA bat. 156 13115 St-Paul-lez-durance Email: david.pignol@cea.fr Phone: +33 (0)4 42 25 30 60 Objectives We propose an integrated and transportable device allowing for the quick detection of numerous pollutants by non-specialists. Our approach consists in a bio- or chemiluminescente or fluorescent measure of a biological or biochemical interaction between a contaminant and a biological recognising element. The objective is to allow the control of the level of contaminants “anywhere, anytime and by anybody”. The project aims at transferring the technologies developed in our laboratories to a in-line measurement device that will benefit from the sensitivity and specificity of the biosensors. Innovative assets The innovative aspect of this project is multiple since it offers systems able to provide a very fast response and can be used by any user. It can be adapted to different systems to be detected (chemical pollutants, microorganisms and toxins) and aims to: • Check upstream of a water treatment plant; • Monitor water quality of a wastewater treatment; • Ensure the control of sensitive river corresponding to drinking water storage; • Control of drinking water networks; • Monitor the quality of water used for raising aquatic animals ; • Prevent emerging threats such as bioterrorism. Discovery and design of new antigens for vaccines conferring broad spectrum protection against leptospirosis Year Start: 2012 Call for projects: FUI (FUI AAP14) Global budget: 6 116 k€ Public funding: 1 908 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research, Discovery Accredited by: Lyonbiopole Abstract Leptospirosis is a neglected bacterial disease affecting humans and various mammals with a high mortality rate. Vaccination is the most effective prevention strategy but most current vaccines do not protect against new serovars emerged in the past few years. COVALEPT will isolate and characterize virulent circulating strains from the field. Protective antigens conserved amongst Leptospira will be identified by bioinformatics, produced in native or recombinant form and assessed in vivo in order to conceive a broad spectrum vaccine for multi-species applications. Strategic business area Application fields Infectious diseases Technological approaches / Keywords Bioinformatics / Software / Biomanufacturing / Genetics / Genomics / Vector vaccine / Antigen discovery Actual outcomes Our prototype for the detection of toxic compounds could be used in the future in several environmental sites, and will be first tested out of the lab in the following months in a water treatment station © COMBITOX Actual Outcomes The project started a little over a year and advance in a highly satisfactory manner. The actions implemented in recent months after the original plan and the results match the expected 18 LYONBIOPOLE milestones. This should allow us to obtain a functional prototype in the next 6 months. Prototype 1 Construction of a prototype for the biodetection of heavy metals (Cd, Hg, As, Ni, Co), toxins and bacteria is in progress. Perspectives Search for public funding Funds for the miniaturization of our prototype will be researched at the end of the project 1 PhD 2 Job creations in Rhône-Alpes region 4 Press releases Investissements: Thermocycler, DNA extractor, Microscope Perspectives Search for technologies Clinical trial realization PARTNERS Partners erial (Company) M enostar (Company) G ALIXAR (Company) C X’Therapeutics (Company) P nstitut Pasteur - Unité de Biologie I des Spirochètes (Research unit) etAgro Sup - Laboratoire des V Leptospires (Research unit) Public funders onseil général de l’Isère C EDER Rhône-Alpes F onds Unique Interministériel (FUI) – F DGCIS/Oséo rand Lyon G renoble Alpes Métropole G ille de Grenoble V Project leader Cupillard Lionel Entity: Merial Position: RD Leader Address: 254, rue Marcel Mérieux RD BP 39H - 69007 Lyon Email: lionel.cupillard@merial.com Phone: +33 (0)4 72 72 55 27 ongoing projects Design of a multi-parametric instrument continuous measurement of toxic compounds COVALEPT Objectives Providing: • leptospirosis vaccine candidate for dogs and potentially other species, A • ioinformatics, molecular and biochemical tools that could accelerate the discovery B and development of other bacterial antigen targets Innovative assets • ew broad-spectrum vaccines against N Leptospirosis; • ollection of virulent circulating Leptospira strains C directly isolated from infected dogs; • ew genetic tools for Leptospira, insights into N biology and virulence mechanisms of atypical bacteria; • ew software and services offers for bacterial N protective candidates selection and antigen design; • ationally designed extraction reagents based on R chemistry of native membrane proteins; • ptimized host/vector couples for recombinant expression of membrane proteins O Product marketing TESTIMONY Nathalia BOMCHIL, Merial “Broad-spectrum vaccines against Leptospirosis, a worldwide severe human and veterinary infection, would constitute a key commercial and sanitary advantage on the market. This scientific and technical challenge requires the input of complementary expertise. COVALEPT was built to achieve such synergy: the partners met regularly during one year, from initial brainstorming to final submission. We had the chance to be supported by Lyonbiopole who helped us define the deliverables and organization of the project. We designed a “win-win” setup, in which each partner develops innovative technologies in its core-business while the leader benefits from the multidisciplinary environment. The importance of the zoonosis and the strong collaborative mindset probably led to the funding of the project.” LYONBIOPOLE 19
  11. 11. DDELPHES An innovative automated system for online detection of microorganisms in water Year Start: 2011 Call for projects: FUI (FUI AAP11) Global budget: 3 271 k€ Public funding: 1 149 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Co-accredited by: Axelera, Risques Partners Bertin Technologies (Company) Cylergie, Centre de recherche de Cofely (Company) CEA LETI (Research Unit) Ademtech (Company) Amoéba (Company) Suez environnement (Company) Public funders Fonds Unique Interministériel (FUI) – DGCIS/Oséo Grand Lyon FEDER PACA Project leader TROUCHET Daniel Entity: Bertin Technologies Position: Senior Expert Address: 10, bis Avenue Ampère 78180 Montigny-le-Bretonneux Email: trouchet@bertin.fr Phone: +33 (0)1 39 30 60 34 ongoing projects Abstract Objectives Three decrees respectively in 2004 and 2010, impose a follow-up of Legionella in wet cooling towers and sanitary water network. The classic strategy which consists in increase organic and inorganic substance amounts cannot be an answer to the microbiological treatment. Then, DDELPHES proposes to develop a full automated system, enabling analysis of the micro-organisms present in water (bacteria and amoeba). This system will make possible to carry out an uninterrupted follow-up of the microbiological quality of water and, by consequence, better control the treatment application. The objectives are the development of standalone subsystems for Sampling and concentration of the water, DNA preparation and automated qPCR on a chip, and then the development of a standalone integrated device (demonstrator) allowing rapid and insitu analysis of micro- organisms in water systems. The Microbial targets are Legionella spp and pneumophila, Amoebae (Naegleria fowleri, Willaertia). The device will allow for automated water sampling, on-line analysis and results sending within a few hours. It will be tested on field with a view to industrialization and marketing of a product. Localized delivery of chemotherapy induced by ultrasound Year Start: 2013 Call for projects: Proof of concept CLARA Global budget: 1 061 k€ Public funding: 435 k€ Duration: 24 months Stage of development at the beginning of the project: Preclinical development The DDELPHES project aims to develop a standalone, in situ and fast analysis system based on qPCR. Up to now, such devices do not exist. The project will be based on a combination of advanced technologies involving biology, automation and miniaturization in order to obtain a compact, sensitive and robust equipment. Amoeba real time monitoring could allow for “green treatment” using them as biological agents. Partners SERM U1032 (LabTAU) (Research IN unit) aviskills (Company) C entre Léon Bérard (Healthcare unit) C Public funders onseil général de Rhône C rand Lyon G Abstract Acoustic cavitation can be defined as the dynamic of bubbles of vapor under an ultrasonic field. It is clearly established in the literature that cavitation favors transmembrane penetration of molecules and increases the ratio efficacy / toxicity of chemotherapies. The project would allow testing on preclinical models a therapeutic prototype combined with conventional drugs and performing clinical pilot study on selected targets. Strategic business area Innovative assets PARTNERS Application fields Oncology (Breast, Sarcoma) Technological approaches / Keywords Chemotherapy / Ultrasound Project leader LAFON Cyril Entity: INSERM U1032 (LabTAU) Position: Senior investigator - Team leader Address: 151, cours Albert Thomas 69424 Lyon CEDEX 03 Email: cyril.lafon@inserm.fr Phone: +33 (0)4 72 68 19 20 Objectives The present project aims at developing an ultrasonic medical device that could potentialize chemotherapy for the treatment of various cancers. Negative hormone receptors breast cancer (207 000 cases/year) and soft-tissue sarcoma (4000 cases/year) have been identified as potential targets. Both cancers do not respond well to available treatments. The conventional chemotherapies demonstrated their relative efficacy but remain associated to a significant systemic toxicity. The non specific distribution of the cytotoxic drugs results in reduced therapeutic efficacy and side effects. Innovative assets INSERM filed a patent on a method for stabilizing ultrasonic cavitation. The company CAVISKILLS SAS licensed this patent and aims at exploiting this idea by developing a clinical device for delivering chemotherapeutic drugs locally. The goal is to enhance the efficacy the treatment and reduce associated side effects. The treatment is completely non invasive and performed under ultrasound imaging guidance. Strategic business area Health Environment Application fields Health Environment Technological approaches / Keywords Biochips Functional decomposition DDELPHES tasks Actual Outcomes Up to now a standalone concentration device, a sample preparation module and a qPCR module have been developed at the prototype stage. Uptake and extraction protocols and kits have been developed and tested. The limits of detection obtained are better than required for amoeba. For legionella, they are good when bacteria are in clean water but not with cooling tower water, which is an important issue to solve. Product, prototype, service 1 1 concentration module 1 sample prep module+ 1 qPCR module 20 LYONBIOPOLE Sustainable Job creations at the 2 end of the project Perspectives Product marketing Automated concentration module TESTIMONY Daniel TROUCHET, Bertin Technologies “The DDELPHES project addresses a major public health concern (water microbial contamination) and the consortium balance between research, industry and end-users, ensures to have at project disposal the available key technologies necessary to reach its goals, which were the key points for the funding of the project. The partnership has been built mainly through networking and it was already partially set via former projects collaborations when Bertin joined it. Lyonbiopôle participated in the consortium final elaboration, and in particular they helped to find a key partner (Ademtech) and to define the work program. They also contributed to keep the development with a view of industrialization and marketing of a product and facilitated scientific exchanges between experts during the project progress.” Schematic of the Caviskills clinical device for treating soft tissues sarcomas Actual outcomes TESTIMONY Products, prototypes, services Clinical trials Press release Cyril Lafon, senior researcher at LabTAU INSERM Unit For the past few years, LabTAU laboratory has worked in close relationship with the CLB (Léon Bérard Cancer Center), particularly on the clinical application of ultrasounds, and with the CRCL (Cancer Research Center of Lyon) on the transfection theme. In 2011, CLARA allowed its collaborations to catalyze by putting in contact the founders of Caviskills. When CLARA financed CLUB, an emerging Perspectives Set-up of a new RD project Clinical trial realization Product marketing Search for private financing Search for public funding project, partners were able to carry out a preliminary market study, thus allowing us to validate the interest for the technology and to select clinical targets. The interest of the collaboration proposed via the CLARA Proof of Concept program is to be able to bring together complementary regional actors essential to the implementation of such a pluridisciplinary project (academics for engineering sciences and biology with clinicians and industrials). LYONBIOPOLE 21 ongoing projects PARTNERS DELICHIUS NEW
  12. 12. DIVRESCUE Doc Calipso Development of a pronostic biomarker for immuno-depressed cancer patients and of the associated immuno-reconstitution treatment PARTNERS Partners Cytheris (Company) Centre Léon Bérard (Healthcare unit) ImmunID Technologies (Company) Public funders FEDER Rhône-Alpes Fonds Unique Interministériel (FUI) – DGCIS/Oséo Région Rhône-Alpes Région Ile-de-France ongoing projects Abstract Studies in metastatic breast cancer patients have demonstrated that reduced T cell receptor diversity (divpenia) combined with lymphopenia was associated with a poor overall survival. The project will evaluate the immune status of each patient through the measure of combinatorial diversity (ImmunTraCkeR test) and ALC (absolute lymphocyte count) in order to detect immunodeficient “lympho-divpenic” patients. Eligible “lympho-divpenic” patients will benefit of an immunotherapy allowing the regeneration of an immunocompetent immune system through administration of glycosylated cytokine IL-7. Project leader MANUEL Manuarii Entity: ImmunID Position: Chief Scientific Officer Assistant Address: 17, rue des Martyrs 38000 grenoble Email: mmanuel@immunid.com Phone: +33 (0)4 38 78 57 70 Objectives Utilizing an innovative diagnostic and therapeutic approach, DivRescue will develop a new way to treat cancer patients, enabling assessment of their immune deficit characterized by lymphopenia and divpenia and correcting it with interleukin-7. We expect this approach to ultimately lead to an increase in patient survival. Innovative assets The partners will combine their cellular, molecular and bio-computing technologies with their immunological and clinical skills in order to treat patient immune deficits and demonstrate the impact of immune response on clinical response. Targeting an increase in patient survival, this theragnostic approach is the first of its kind in the world. Strategic business area Year Start: 2010 Call for projects: Proof of concept CLARA Global budget: 1 256 k€ Public funding: 627 k€ Duration: 36 months Stage of development at the beginning of the project: Discovery Today, the early diagnosis of small tumors is possible through the use of screening biological tests and medical imaging. In most cases, surgical resection of tumors is the primary means of therapy. Given the poor tolerability of standard surgical treatment, new techniques have been developed. Of these, laparoscopic surgery limits the morbidity of the incision and percutaneous treatment avoids dissection of tissues. However, laparoscopic technique remains limited in terms of accuracy and percutaneous treatment requires constant radiation monitoring and protection. Strategic business area Actual Outcomes Perspectives Products, prototypes, services Clinical trials Press release Set-up of a new RD project Clinical trial realization Product marketing Search for private financing 22 LYONBIOPOLE Search for public funding Project leader COLOMBEL Marc Entity: Centre Hospitalier Universitaire de Lyon Position: Urologist Surgeon Address: Hôpital Edouard Herriot 5, place d’Arsonval - 69003 Lyon Email: marc.colombel@chu-lyon.fr Phone: +33 (0)8 99 96 06 56 Objectives Our project is to introduce a new concept of robots that will automatically locate a treatment probe close to the tumor using an innovative three-dimensional navigation robot that is guided by a tracking sensor implanted in the body and/or that uses image analysis to process. Innovative assets The latest innovations in ablative technologies such as cryotherapy or high intensity focused ultrasounds have been successfully adapted to treat solid tumors. These techniques aimed at focally destroy prostate, kidney, brain, liver… are guided by ultrasound, CT or MRI which are unsatisfactory given a lack of precision and the risk of radiation exposure. The innovative asset of this project is the design a three-dimensional navigation robot capable of targeting a solid tumor with a treatment device taking into account body motion (i.e. breathing) in real-time with an accuracy below 1 mm. DocCalipso three-dimensional navigation robot © 1996-2013 Adept Technology, Inc. ImmunID Forecast Station “IFS” for the detection of Divpenia Actual outcomes Partners dept (Company) A ospices Civils de Lyon (Healthcare H unit) Public funders EDER Rhône-Alpes F Région Rhône-Alpes Abstract Application fields Oncology Technological approaches / Keywords Drug delivery system / Imaging (medical) Application fields Oncology Technological approaches / Keywords Genetics / Genomics / Immunotherapy (PCR and NGS) PARTNERS If successful, this generation of surgical tools will mark a new step in medical engineering for its remarkable precision, and the possibility to adapt the system to many applications in cancer treatment (ablation, injection, tracking..). This projects was made realizable by the merging of our two clinical and robotic engineering and very motivated teams. We seized this unique opportunity to realize our dreams that robotic assisted tracking will represent the next breakthrough in cancer treatments. Perspectives Preclinical assay realization Starting by the end of 2013 Proof of concept 1 Three-dimensional navigation robot LYONBIOPOLE 23 ongoing projects Year Start: 2011 Call for projects: FUI (FUI AAP11) Global budget: 4 395 k€ Public funding: 2 572 k€ Duration: 42 months Stage of development at the beginning of the project: Clinical trials Accredited by: Lyonbiopole Co-accredited by: Medicen Paris Region Robot navigation for tumor focal therapy
  13. 13. DORGAN EMER-FAB Year Start: 2012 Call for projects: ANR (ANR2011 - TECSAN) Global budget: 1988 k€ Public funding: 875 k€ Duration: 36 months Stage of development at the beginning of the project: Preclinical development Accredited by: Lyonbiopole ongoing projects Abstract In external beam radiotherapy and brachytherapy, verification of the delivered dose at the target volume during each radiotherapy session and for the whole treatment is a key issue for quality assurance. To be reliable, this dosimetric monitoring must be independent of the dose delivering system and obtained in real-time. In interventional radiology, the skin entrance dose must be determined in real-time. Also emerging radiotherapy modalities require reliable dosimetry. The DoRGaN project proposes to develop a multi-channel dosimetry system based on the use of GaN radioluminescent transducers. Strategic business area Application fields Oncology / Medical physics Technological approaches / Keywords Minimally Invasive Technologies / Radiotherapy / Dosimetry Actual Outcomes Real-time dosimetry system prototypes for independent in vivo dose assessment and efficient quality assurance have been developed for brachytherapy and small field radiotherapy. This is an important step towards “dose guided” procedures for best clinical outcome with the lowest toxicity level. The new developed quality assurance instrument is relevant for patient safety in current procedure and becomes of key importance when new technology and practice are introduced at the same time. 24 LYONBIOPOLE PARTNERS Partners Institut des Nanotechnologies de Lyon, UMR5270 (Research unit) Hospices Civils de Lyon (HCL) - Service de Radiophysique et Radiovigilance (Healthcare unit) CHU de Grenoble - Service de Radiothérapie (Healthcare unit) DOSILAB (Company) Public funders ANR, Agence Nationale de la Recherche Project leader PITTET Patrick Entity: Institut des Nanotechnologies de Lyon Position: Research Engineer Address: Bât. Brillouin, 43, Bd du 11 novembre 1918 - 69622 Villeurbanne Email: patrick.pittet@univ-lyon1.fr Phone: +33 (0)4 72 44 62 82 Objectives • Support ongoing work on real-time in situ dosimetry for demanding applications such as IMRT with small irradiation fields and high dose gradients • Iinvestigate GaN dosimetry potential for emerging therapies such as hadrontherapy • Develop real-time in vivo dosimetry for PDR and HDR brachytherapy • esign GaN dosimeter arrays to detect the maximum skin dose area during D interventional radiology procedures in real-time • rovide an user-friendly system for QA of dose delivery systems and giving clear and P real-time patient dose exposure data to the medical staff at an attractive cost. Products, prototypes 2 Brachytherapy instrumented phantom (currently setup at the HCL) - Small field radiotherapy instrumented phantom (in manufacturing) Scientific publications 2 Communications in international 5 congresses 1 PhD 1 License Agreement An exclusive licence agreement on the SECURIDOSE technology has been signed between DOSILAB on one side and Université Lyon 1, Université Joseph Fourier, CHU de Grenoble, CPE Lyon on the other side Year Start: 2011 Call for projects: FUI (FUI AAP10) Global budget: 2 486 k€ Public funding: 1 357 k€ Duration: 36 months Stage of development at the beginning of the project: Preclinical development Accredited by: Lyonbiopole Abstract The project is dedicated to the development and the regulatory validation of an original and complete model for the development and production of immunotherapeutic solutions against the CCHF virus (Crimean Congo Hemorrhagic Fever). The virus causes severe hemorrhagic fever. It occurs in Africa, Eastern Europe and Turkey, where it represents, in the absence of any satisfactory therapeutic solution, a public health issue for those who are directly exposed, in particular healthcare workers. Strategic business area Innovative assets The DoRGaN project develops real time dosimetric systems based on the patented Securidose technology. The GaN radioluminescent transducer yields a high real time signal from a small detecting volume and is suitable for use in small fields and for high dose gradients. New instrumented phantom prototypes have been designed and characterized for quality assurance during brachytherapy and small field radiotherapy for independent real time treatment verification. Development, regulatory validation and production of new specific polyclonal immunoglobulin against the Crimean Congo Hemorrhagic Fever Virus (CCHFV) Application fields Infectious diseases Technological approaches / Keywords Immunotherapy / Vector vaccine PARTNERS Partners AB’ENTECH (Company) F anofi Pasteur (Company) S aboratoire Jean Mérieux P4 Inserm L (Research unit) entre international de recherche C en infectiologie (CIRI) Inserm U1111CNRS UMR5308 (Research unit) Public funders onds Unique Interministériel (FUI) – F DGCIS/Oséo rand Lyon G Project leader LEPINE Bertrand Entity: Fab’entech Position: CEO Address: 321, avenue Jean-Jaures 69007 LYON Email: bertrand.lepine@fabentech.com Phone: +33 (0)4 37 70 69 67 Objectives • dentify and select the appropriate CCHF viral strain among various circulating I species. • evelop CCHF antigens to be used for horse hyperimmunisation (VLP...) D • alidate a Proof of concept both in vitro (development of specific in vitro assays) and in V vivo (development of an animal model for CCHF infection by the BSL-4 laboratory). • evelop a GMP assay to quantify the activity of specific anti-CCHF antibodies for the D release of clinical and commercial batches. • roduction of specific polyclonal immunoglobulin against the CCHF virus. P Innovative assets • Development of Virus-Like-Particule CCHF • DNA vectorization of VLP • Production and purification of specific anti-CCHFV immunoglobulins • Development of in vitro and in vivo tools for CHCF laboratory-studies Instrumented phantom prototype for brachytherapy quality assurance © Pierrick Guiral 1 Job creation in Rhône-Alpes region Perspectives Set-up of a new RD project Preclinical assay realization Clinical trial realization Product marketing Actual outcomes • Validate the initial proof-of-concept on anti-CCHFV F(ab’)2 by in vitro seroneutralization assays and in vivo assays on IFNAR-/- mice. • evelop a specific validated ELISA and D establish a correlation between ELISA values and F(ab’)2 efficacy • evelop VLP CCHF based tools such as D ELISA, or cellular entry tests • Vectorization of CCHF VLP for DNA immunization in horses Products, prototypes, services Proof of concept Perspectives Search of partnership Search for technologies Preclinical assay realization Search for private financing LYONBIOPOLE 25 ongoing projects Dosimetry by Radioluminescence of GaN for in vivo real-time patient dose assessment for radiotherapy, brachytherapy and interventional radiology
  14. 14. ETICS NEW Accelerated development program of immunotherapy solutions against emerging diseases Year Start: 2012 Call for projects: ISI Oséo Global budget: 26 620 k€ Public funding: 9 507 k€ Duration: 63 months Stage of development at the beginning of the project: Discovery Accredited by: Lyonbiopole ongoing projects Abstract The EMER-IT program proposes to build a complete value chain for developing, producing and commercializing innovative specific polyclonal immunoglobulins against at least four emerging pathogens (such as Encephalitis of Nipah, Ebola hemorrhagic fever or Lassa, SARS). These specific polyclonal immunoglobulins will be produced with an ambitious immunization approach that will be implemented by using synthetic nanovectorization of antigens in DNA form. The proof of concept of efficacy of each specific polyclonal immunoglobulin product will then be established. PARTNERS Partners AB’ENTECH (Company) F n-Cell-Art (Company) I IRI - equipe Enveloppes virales et C ingéniere des rétrovirus (Research team) Laboratoire Jean Mérieux P4 - Inserm (Research unit) Institut du thorax (Inserm U915) (Research unit) Public funders Oséo / BPI France Project leader VACHER Laurent Entity: Fab’entech Position: RD programs leader Address: Immeuble Domilyon, 321, Avenue Jean Jaures - 69007 Lyon Email: laurent.vacher@fabentech.com Phone: +33 (0)4 37 70 67 67 Objectives • Identify and select the appropriate strains of highly pathogenic viruses according to epidemic needs and health risks • Develop, manufacture and commercialize specific polyclonal immunoglobulins against emerging infectious diseases • Develop an innovative antigen approach using synthetic DNA nano-vectorization of VLP to be used for horse hyperimmunization against any emerging pathogens targeted • Implement a pilot plant for the GMP production of specific polyclonal immunoglobulin products • Develop a new DNA-based veterinary vaccine for horses by In-Cell-Art Innovative assets Strategic business area Application fields Infectious disease Technological approaches / Keywords Immunotherapy • DNA-based antigen nano-vectorization • Virus-Like Particles (VLP) nano-vectorization • Innovative platform for the develoment and flexible production of specific polyclonal immunoglobulins • Single-use based pilot plant for GMP production of immunoglobulins Evolved Tissue Inspired Cell Systems Year Start: 2011 Call for projects: ISI Oséo Global budget: 14 400 k€ Public funding: 7 600 k€ Duration: 60 months Stage of development at the beginning of the project: Preclinical development Accredited by: Lyonbiopole PARTNERS Partners YTOO Cell Architects (Company) C ellectis (Company) C EA iRTSV France (Research unit) C Public funders séo / BPI France O Entity: CYTOO SA Position: CEO Address: MINATEC -BHT-B52 - 7 Parvis Louis Néel - BP50 - 38040 Grenoble Email: mlebozec@cytoo.com Phone: +33 (0)4 38 88 47 05 Abstract The use of more relevant cells during pharma-tox screening would help the search for new drugs and pick up toxicity issues earlier. Conversion however to 3D cell culture represents a huge challenge as it is badly adapted to the constraints of automated screening and high content imaging and analysis. The ETICS program aims at providing an alternative option: combine the potential of adhesive micropatterns, soft substrates and standardized fluorescent cell lines enabling more physiological cellular models and reliable high content imaging and analysis optimized for pharma-tox drug screening. Project leader LEBOZEC Marc Objectives The ETICS program aims to provide cell models that are more physiologically relevant as well as better suited for high content imaging and analysis (HCA) than conventional methods. This will be obtained by cultivating cells on micropatterned surfaces with softness properties similar to the original tissue. Specific fluorescent cells lines expressing standardized levels of fluorescent proteins will be used to demonstrate that more meaningful and reproducible experimental results are obtained under these conditions. Strategic business area Application fields All pathologies area Technological approaches / Keywords Cell model / Genetics / Genomics A model illustrating the combination of soft surfaces, adhesive micropatterns and fluorescent cells Human epidemics recorded for 6 emerging diseases Actual Outcomes Products, prototypes, services Clinical trials Product on the market Job creation in Rhône-Alpes region 26 LYONBIOPOLE Perspectives Search of competences Product marketing LYONBIOPOLE 27 ongoing projects EMER-IT
  15. 15. FEMTOKINE FLUMA Year Start: 2010 Call for projects: FUI (FUI AAP10) Global budget: 2 170 k€ Public funding: 1 267 k€ Duration: 48 months Stage of development at the beginning of the project: Clinical trials Accredited by: Lyonbiopole Co-accredited by: Eurobiomed ongoing projects Abstract PARTNERS Partners DICIA BIOTECHNOLOGY (Company) IN ospices Civils de Lyon (Healthcare H unit) xCell (Company) T INGULEX (Company) S Public funders FEDER Rhône-Alpes Fonds Unique Interministériel (FUI) – DGCIS/Oséo Grand Lyon Région Rhône-Alpes Project leader LEGASTELOIS Stéphane Entity: Indicia Biotechnology Position: CEO Address: 33, avenue de la Californie 69600 Oullins Email: slegastelois@indicia.fr Phone: +33 (0)4 72 39 14 92 Different conformations of the Influenza virus matrix protein M1 and their role during entry and budding Year Start: 2011 Call for projects: ANR (ANR2010 - BLANC) Global budget: 314 k€ Public funding: 212 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole • Biobanking: patients in clinical remission induced by surgical or drug therapeutic management and patients under cellular therapy • Immunoassay validation following FDA guidelines • New immuno-assay development • Kit’s adaptation for intestinal biopsy diagnostic • Samples analysis to validate immunological biomarkers as predictors of clinical recurrence of CD: - T cell analysis in blood and in biopsies - Determination of immunological markers in plasma and biopsies - Measurement of inflammation markers in serum and stools Influenza viruses contain three major subviral components: the envelope, matrix protein 1 (M1) and the core harboring the RNA genome. M1 forms a shell beneath the viral envelope that sustains the virion architecture. Upon acidification of the virion within the endosomes, M1 undergoes a conformational change resulting in disassembly of the M1 matrix, virus uncoating and the release of the vRNP into the host cell. The project aims to elucidate the structural basis of M1 activation of Influenza virus assembly and budding and establish the exact roles of M1 during these processes. Strategic business area Innovative assets Strategic business area Application fields Autoimmune diseases Technological approaches / Keywords Biobank / Immunomonitoring • High sensitive immunoassays for the prediction of relapses of Crohn’s disease and therapeutic follow –up. • Clinical validation of biomarkers Technical development and clinical validation of immunoassays. Application fields Infectious diseases Technological approaches / Keywords Structural Biology The accuracy of immunologic biomarkers to predict the relapse of CD might be superior to that of inflammatory markers and requires ultrasensitive methods for immunomonitoring immune responses. Actual Outcomes testominy 1 Product, prototype, service Communication in international 1 congress License Agreement 1 Sustainable Job creations at the 2 end of the project 1 Job creation in Rhône-Alpes region 1 Start-up Creation Creation of Singulex Europe subsidiary in 2010 Increase in turnover Stéphane LEGASTELOIS, Indicia “Singulex and Indicia signed a partnering agreement by which Indicia acquired the rights to use the new Singulex’s Erenna Immunoassay platform. The technology is dedicated to the measurement of cytokines and other biomarkers at the femtogramme level. This level of performance makes possible the monitoring of immunological disorders in human inflammatory diseases such as Crohn disease 28 LYONBIOPOLE Femtokine was built around partners having access to human patients suffering from Crohn disease. Hospices Civils de Lyon and TxCell were both conducting clinical trials on this pathology. Singulex RD Europe provides the technology while Indicia offers the Immunoassay plateform and sample analysis. Lyonbiopole gave significant support to identify partners, prepare the project submission file and give assistance in the follow-up of the project” Partners nit of Virus Host Cell Interactions U UMI 3265 (Research unit) Public funders NR, Agence Nationale de la A Recherche Project leader WEISSENHORN Winfried Entity: Unit of Viral Host Cell Interaction (UVHCI) Position: Professor, team leader Address: 6, rue Jules Horowitz, BP181 F-38042 Cedex 9 Grenoble Email: weissen@embl.fr Phone: +33 (0)4 76 20 72 81 Abstract Femtokine aims to develop tools dedicated to the identification and validation of immunological biomarkers that are specifically involved in Crohn Disease (CD), a chronic inflammatory pathology of the digestive tract. The disease suffers from a lack of non invasive biomarkers that are needed to assess the severity of the pathology, together with the efficacy and toxicity of therapeutic treatments. The project consists of generating a bank of samples from CD patients, measuring and validating a panel of biomarkers based on an unique and ultra-sensitive proteomic plate-form. Objectives PARTNERS Objectives • stablish the cloning, expression and purification of full-length M1 protein derived from E different Influenza strains. • creen for crystallization conditions for full-length M1 protein at neutral and low pH. To S facilitate crystallization of M1 in different conformations we will generate conformation specific llama VHH nanobodies and try co-crystallization with known complex partners. • Determination of high resolution structures of full-length M1protein. • stablish conditions that allow us to study protein coat formation by M1 in vitro. E Innovative assets The project concentrates on the structural biology of the complete viral matrix protein M1. We hypothesize that the crystal structure of a complete M1 protein will provide important insight into its function during uncoating and during assembly and budding. Our work might provide novel insight into the ESCRT-independent budding of influenza virus and the structural details of M1 at neutral and low pH will help to develop anti-viral agents that target entry or assembly. Schematic model of an influenza virion. The matrix protein M1 has an elongated shape in solution (inset M1 model based on SAXS data) and forms a protein layer underneath the viral membrane. During entry this protein coat must dissassemble to allow establishment of a new infection. Actual Outcomes •W e have shown by NMR that the matrix protein M1 undergoes conformational changes at endosmal pH, which may be important for uncoating. • e have solved the crystal structure of W M1 from influenza C, which resembles globally the structure of M1 from influenza virus A. • e have assemble low resolution W models of influenza virus A and C based on SAXS data. • e have analyzed the membrane binW ding properties of influenza virus A and C M1 proteins Perspectives Search for public funding Part of the project is funded by the Labex GRAL 1 Manuscript in preparation LYONBIOPOLE 29 ongoing projects High sensitive immunoassays for the prediction of relapses of Crohn’s disease and therapeutic follow –up. Clinical validation of biomarkers Technical development and clinical validation of immunoassays
  16. 16. FLUNUCLEOVIR NEW Development of new antiviral drugs against the nucleoprotein from Influenza A viruses PARTNERS Partners Virologie et Immunologie Moleculaires, UR892 INRA (Jouy-enJosas (Research unit) Unit of Virus Host Cell Interactions UMI 3265 (Healthcare unit) Public funders ANR, Agence Nationale de la Recherche ongoing projects Abstract We identified the novel antiviral activity of naproxen, a known anti-inflammatory drug, based on initial in silico screening studies. Naproxen binds to the RNA binding site of NP, thereby impeded NP function requiring association with viral RNA. Its antiviral effect was demonstrated by its protection of MDCK cells and mice against a viral challenge. Naproxen and its novel derivatives stabilized NP in a monomeric form and avoided NP oligomerization.The structure of a mutant R416A NP was solved that led to a model of stabilization of NP monomers by introduction of a charge in S165D. Strategic business area Application fields Infectious diseases / Inflammatory diseases / Health Environment Technological approaches / Keywords Cell model / Animal model / In silico modeling / Structural Biology Project leader SLAMA-SCHWOK Anny Entity: VIM, INRA Position: INSERM Researcher Address: Domaine de Vilvert 78350 Jouy-en-Josas, France Email: Anny.Schwok@jouy.inra.fr Phone: +33 (0)1 34 65 26 15 Objectives • A first goal is the structural understanding of NP- RNA interactions leading to (i) the control of NP oligomerization (ii) more insight into structure-function relationships of the ribonucleoprotein complex formed by the assembly of NP, RNA and the polymerase subunits; • A second goal is to develop novel antivirals targeting the nucleoprotein using a structure-based approach. Fluorescence and Robotics for laparoscopic surgery Year Start: 2012 Call for projects: FUI (FUI AAP13) Global budget: 3 244 k€ Public funding: 1 564 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Minalogic Co-accredited by: Lyonbiopôle, Medicen Paris Region Abstract The project will develop an endoscopic imaging system to visualize areas of interest both with fluorescence and colors. This objective requires the miniaturization of fluorescence imaging systems. The project also aim to develop a robotic arm that will bring stability, precision and guidance of surgical gesture. Strategic business area Innovative assets Application fields Oncology Technological approaches / Keywords Imaging (medical) / Minimally Invasive Technologies • Novel strategy for antivirals developpment as the lead compound naproxen that stabilize the monomeric form of Influenza A nucleoprotein and impede its oligomerization required for function of its complex with the polymerase • Novel X-ray structure of NP in a monomeric form • Naproxen target critical residues for NP function; we could not identify viral escape to naproxen PARTNERS Partners DOCONTROL (Company) EN luoptics (Company) F EA LETI (Reseach unit) C aption (Company) H utualiste Montsouris (Healthcare M unit) niversité Paris 6 (Research unit) U niversité Joseph Fourier (Research U unit) Public funders EDER Rhône-Alpes F onds Unique Interministériel (FUI) – F DGCIS/Oséo Région Rhône-Alpes Ville de Grenoble Project leader BARDOU Bérengère Entity: ENDOCONTROL Position: Scientific project manager Address: 5, Avenue du Grand Sablon 38700 La Tronche Email: berengere.bardou@endocontrol-medical.com Phone: +33 (0)4 76 63 75 83 Objectives The aims of FluoRoMIS project is to study and develop the following innovative technologies: an endoscopic device for fluorescence imaging (and its 3D version) and a robotic arm for comanipulation of surgical instrument. The final goal of the project is to combine both technologies: the robotic arm will guide and secure surgeon movements based on information extracted from fluorescence images. Innovative assets • fluorescence imaging device for minimally invasive surgery to highlight area of A interest (tumor, organs…). • robotic arm and its control laws for comanipulation of surgical instruments, a new A concept of robotic assistance  leaving the surgeon close to the patient. • platform combining both technologies by guiding the robotic arm with fluorescence A imaging. X-ray structures of the nucleoprotein of Influenza A in various forms: a: monomer, b: dimer, c: trimer, d: tetramer e: monomer with naproxen The Future of MIS © EndoControl / Fluoptics / Haption Actual Outcomes TWO in ONE: Naproxen as an anti-inflammatory and antiviral compound Evidence for a monomeric form of the nucleoprotein of Influenza A virus and the ways to stabilize it, impeding its interactions with RNA, characterization of the structure of a monomer prototype, the R416A mutant. 30 LYONBIOPOLE 1 Product, prototype, service 1 Proof of concept Patent 1 5 Scientific publications Job creation in Rhône-Alpes region 1 Press release 1 Perspectives Search for private financing We search for partners to develop new antivirals against the nucleoprotein and RNP assembly. Search for public funding We will request public funds from ANR Actual Outcomes Perspectives Products, prototypes, services Product on the market Sustainable Job creation at the end of the project Job creation in Rhône-Alpes region Increase in turnover Press release Clinical trial realization Product marketing LYONBIOPOLE 31 ongoing projects Year Start: 2010 Call for projects: ANR (ANR2010 - BLANC) Global budget: 1 694 k€ Public funding: 500 k€ Duration: 36 months Stage of development at the beginning of the project: Basic research Accredited by: Lyonbiopole Co-accredited by: Medicen Paris Region FLUOROMIS II

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