Annual Meeting of the Doctoral School «Biologie-Santé» Nantes/Angers - PDF

0 and December 05 Oniris Chantrerie, Nantes Annual Meeting of the Doctoral School «Biologie-Santé» Nantes/Angers with the participation of Nantes and Angers PhD students Journées Scientifiques de l Ecole

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0 and December 05 Oniris Chantrerie, Nantes Annual Meeting of the Doctoral School «Biologie-Santé» Nantes/Angers with the participation of Nantes and Angers PhD students Journées Scientifiques de l Ecole Doctorale Biologie-Santé Nantes-Angers 08:00 09:00 09:30 :40 3:00 4:00 5:40 6:00 7:40 9:00 :00 THURSDAY 0 DECEMBER PARTICIPANTS ARRIVAL WELCOME INTRODUCTION PLENARY SESSION Nanomedicine - Bioinformatics Gene & Cell Therapy COFEE BREAK - POSTER SESSION LUNCH PLENARY SESSION Infectious diseases - Applied Immunology COFEE BREAK PLENARY SESSION Cancerology PLENARY SESSION 3rd year PhD students session DINNER AFTER-PARTY 08:30 09:30 :0 3:00 4:00 5:40 6:30 7:00 FRIDAY DECEMBER PARTICIPANTS ARRIVAL PLENARY SESSION Cardiovascular diseases - Signalisation COFEE BREAK - POSTER SESSION LUNCH PLENARY SESSION Nutrition - Metabolism COFEE BREAK - BEST PRESENTATIONS AWARDS MEETING CLOSURE RETURN THURSDAY 0 DECEMBER - MORNING 09:00 09:30 WELCOME INTRODUCTION Doctoral School Introduction DNA-Biosanté association presentation Corrine MIRAL Julien FLEURENCE 09:30 :40 PLENARY SESSION Nanomedicine Bioinformatics Gene & Cell Therapy 09:30 0:30 ZELZER Mischa Nottingham (UK) Nature or nurture What determines the performance of biointerfaces? 0:30 :40 Selected short oral presentations (0 minutes + questions) DENARNAUD Alison UMR-S INSERM 066 Angers First assesment of the diffusion coefficient of nanocarriers with the fluorescence recovery technique in the gastrointestinal mucus. SAURY Charlotte UMR INRA/Oniris 703 Nantes Human MuStem cell, a cell therapy candidate for Duchene Muscular Dystrophy (DMD) : from reasearch to clinical-grade production HENDRICKX Johan UMR CNRS 686 Nantes Methodologic development for studies of protein-carbohydrate interaction phenomena VETRIVEL Iyanar UMR CNRS 686 Nantes Predicting and analyzing protein structures using a structural alphabet :40 3:00 COFEE BREAK VISIT OF EXHIBITION POSTER SESSION 3:00 4:00 LUNCH THURSDAY 0 DECEMBER - AFTERNOON 4:00 5:40 PLENARY SESSION Infectious diseases Applied Immunology 4:00 4:30 ALVAREZ Nidia Nantes (FR) Immune response against fungal diseases 4:30 5:40 Selected short oral presentations (0 minutes + questions) STAERCK Cindy UPRES EA 34 Angers Oxidative stress defense of Scedosporium apiospermum, a filamentous fungus associated with cystic fibrosis BELARIF Lyssia UMR INSERM 064 Nantes IL-7 receptor blockade prevents intestinal human T cells infiltration by modulation of alpha4-beta7 integrin expression GERGEN Janina UMR INSERM 064 Nantes A new antiviral strategy against HCMV using genome editing tools SIKORSKI Mathieu UMR INSERM 064 Nantes Human myeloid dendritic cells can interact with BK polyomavirus and transfer it to permissive cells 5:40 6:00 COFEE BREAK VISIT OF EXHIBITION 6:00 7:40 PLENARY SESSION Cancerology 6:00 6:30 FONTENEAU Jean-François Nantes (FR) Oncolytic virotherapy with attenuated Measles Virus 6:30 7:40 Selected short oral presentations (0 minutes + questions) NADER Joelle UMR INSERM 89 Nantes Experimental mesotheliomas in F344 rats : tools of investigation for basic reasearch in oncoimmunology, diagnosis and evaluation of new therapeutic strategies. DEGORRE Charlotte UMR INSERM 89 Nantes Deciphering radiation-induced microvascular endothelial cell senescence POURBAGHI MASOULEH Milad UMR-S INSERM 066 Angers Mesenchymal stem cells as cellular vehicles for delivery of drugloaded nanoparticles to brain tumors via the nasal route GILLARDIN Pierre-Samuel UMR INSERM 89 Nantes Epigenetic regulation of p53-gene-family 7:40 9:00 3 rd YEAR PhD STUDENTS SESSION (0 minutes + questions) BEY Karim UMR INRA/Oniris 703 Nantes Intrathecal gene therapy using raav9-hsmn vector to treat moderate forms of SMA. DAVID Benoit UMR CNRS 686 Nantes Turning Glycoside hydrolase into transglycosidase : a theoretical and experimental study if the internal water dynamics in the Thermus thermophilus ß-glycosidase. 9:00 :00 DINNER Le Carré Gourmand La Chantrerie, Nantes :00 0:00 AFTER-PARTY Animation by DNA BioSanté association Shuttle service provided to join the hotels 3 FRIDAY DECEMBER - MORNING 09:30 :0 PLENARY SESSION Cardiovascular diseases Signalisation Osteoarticular diseases 09:30 0:00 SAUZEAU Vincent Nantes (FR) RAC: a new therapeutic target in the asthma treatment. 0:00 :0 Selected short oral presentations Caridovascular diseases (0 minutes + questions) GUIVARC H Emmanuel UMR INSERM 083/CNRS 64 Angers Protective role of the oestrogen receptor alpha in hypertension BAKHTA Oussama EA 3860 Angers The involvment of a coktail of amino acids in remote ischemic preconditioning induced cardioprotection in acute myocardial infarction Selected short oral presentations Osteoarticular diseases (0 minutes + questions) LE TILLY Elodie UMR INSERM 79 Nantes Role of the anti-aging protein Klotho in the autophagy and senescence-associated development of osteoarthritis KÜN-DARBOIS Jean-Daniel Upres EA 4658 Angers Botulinum toxin in masticory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the madible associated with a bone proliferation at a muscle enthesis CLOITRE Alexandra UMR INSERM 79 Nantes A potential role for interleukine 38 (IL-38) in peridontis? :0 3:00 COFEE BREAK VISIT OF EXHIBITION POSTER SESSION 3:00 4:00 LUNCH 4 FRIDAY DECEMBER - AFTERNOON 4:00 5:40 PLENARY SESSION Nutrition - Metabolism 4:00 4:30 Le LAY Soazig Angers (FR) Emerging roles of extracellular vesicles in the regulation of adipocyte metabolism 4:30 5:40 Selected short oral presentations (0 minutes + questions) NDJIM Marième UMR PhAN 80 Nantes Intrauterine growth restriction (IUGR) induces a loss of vagal sensitivity to cholecystokinin TRENTESEAUX Charlotte UMR PhAN 80 Nantes Modulation of atherosclerosis by nutritional approach LAGALICE Lydie UMR INRA/Oniris 703 Nantes Therapeutic potential of Muscle-Derived Stem Cells in Pompe disease (Glycogenosis type II) BEN ROMDHANE Racem UMR INRA/Oniris 300 Nantes Effect of variation in phenotypic traits of dairy cattle resistance to Map exposure at a herd scale : modelling approach 5:40 6:30 COFEE BREAK BEST PRESENTATIONS AND POSTERS AWARDS 6:30 6:45 MEETING CLOSURE 7:00 RETURN TO NANTES OR ANGERS 5 ORAL COMMUNICATIONS BAKHTA Oussama PhD student nd year - EA3860 Laboratoire de Cardioprotection, Remodelage et Thrombose (CRT), Angers The involvement of a cocktail of amino acids in remote ischemic preconditioning induced cardioprotection in acute myocardial infarction Oussama Bakhta*,, Juan Manuel Chao de la Barca, MD,3,4, Delphine Mirebeau-Prunier, MD, PhD,3,4, Sophie Tamareille, PhD,, Gilles Simard, MD, PhD,3,5, Cédric Gadras, MLT 3, Pascal reynier, MD, PhD,3,4, and Fabrice Prunier, MD, PhD, : Laboratoire de Cardioprotection, Remodelage et Thrombose, EA3860, Faculté de Médecine, Angers, France : Université d Angers 3 : Département de Biochimie et Génétique, CHU, Angers, France 4 : BNMI, UMR INSERM 083 CNRS 64, Angers, France 5 : SOPAM UMR INSERM 063 Background Remote ischemic preconditionning (RIPC) has emerged as an attractive therapeutic procedure to protect the heart against ischemia/reperfusion (I/R) injury. Despite strong evidences of the critical role played by circulating humoral mediators for signal transduction, their identities still remain unknown. Using a targeted metabolomic approach we previously identified Glycine and Kynurenine as potential mediators for RIPC induced in both rats and humans. Aim of the study This study sought to determine whether a treatment with Glycine and Kynurenine alone or in combination could mimic the cardioprotective effect of the RIPC Methods Male Wistar rats, 8-0 weeks exposed to myocardial I/R were allocated to one of the following six groups: Myocardial Infarction (MI), rats were subjected to myocardial I/R without any further intervention; RIPC+MI, four cycles of limb I/R were applied prior to the myocardial ischemia; Metabolites+MI, with intraperitoneal injection of a combined Glycine (0.5mg/g body weight) and Kynurenine (0.3 mg/g body weight) 0 min before MI; Vehicle+MI, with intraperitoneal injection of the vehicle 0 min before MI; Glycine+MI, with intraperitoneal injection of single dose of Glycine 0 min before MI; and Kynurenine+MI, with an intraperitoneal injection of single dose of Kynurenine 0 min prior to MI. Hearts were excised after h of reperfusion and the area at risk (AAR) and infarct size (AN) were measured after TTC staining. Glycine and kynurenine plasma concentrations were determined by mass spectroscopy LC-MS/MS at 3 points of time: 5, 30 and 45 minutes after the intraperitoneal injection. Results The metabolites blood assay showed a significant increase of both glycine and kynurenine in blood plasma 5 min after the intraperitoneal injection with a peak at 30 min. As compared to MI, both RIPC+MI and Metabolites+MI exhibited a smaller infarct size (AN/AAR=39.59±3.76% for Vehicle+MI vs. 7.5±4.47% for the Metabolites+MI group, and 4.49±.4% for MI vs ±.8% for the RIPC+MI, both p 0.05). Kynurenine injection alone and Glycine injection alone significantly decreased infarct size (AN/AAR=7.70±.53% in Kynurenine+MI vs. MI group; p=0.004 and 33.4±.30% in Glycine+MI, vs. MI, p=0.07). Conclusion We report that RIPC-induced cardioprotection may involve a cocktail of amino acids for signal transduction from the remote organ to the myocardium. 6 BELARIF Lyssia PhD student nd year UMR INSERM 064, ITUN, Nantes IL-7 receptor blockade prevents intestinal human T cells infiltration by modulation of alpha4-beta7 integrin expression L. Belarif,,*, V. Daguin, M.Florent, N.Poirier,, G. Blancho,3, B.Vanhove, INSERM UMR 064, Nantes, France; Institut de Transplantation Urologie Néphrologie (ITUN), Université de Nantes, Nantes F-44000, France Effimune, Nantes, France 3 Centre Hospitalier Universitaire, Nantes, France Interleukin 7 is a limiting and non-redundant cytokine sustaining T lymphocyte proliferation, survival and homeostasis. Almost all T lymphocytes express the IL-7 receptor (IL-7R), with an exception for natural regulatory T-cells (Treg), constituting an opportunity to selectively target effectors (Teff) while sparing Treg. Furthermore, IL-7R-positive cells and IL-7 secretion are accumulated in inflammatory lesions of inflammatory bowel diseases 3. In this study, we investigated how IL-7 could modulate human T cell homing to the gut. First, we observed that IL-7 alone is a rapid inducer of integrin α4 and β7expression in human but not in mouse T cells in vitro. In contrast, the expression of other integrins interacting with α4 or β7 is not modified by IL-7. We found also that IL-7 is required continuously to maintain α4β7 over-expression and that anti- IL-7R antagonistic mab could prevent it. We next investigated how IL-7 modulates α4β7 expression in human. We found that IL-7 signals directly control the transcription of α4 in human T cells while IL-7 signals modulate β7 expression at a traductional level. The lymphocyte α4β7 integrin being the main intestinal lymphocyte homing receptor, we used NOD SCID Gamma -/- mice that we engrafted with human PBMC to study intestinal xeno-gvhd (graft versus host disease) as a surrogate model of gut inflammation induced by human T cells. Treatment of recipient mice with a novel humanized anti-il-7r antagonistic mab dampened GVHD and extended survival (p 0.0), without impacting level of immune reconstitution. Interestingly, one-week post-treatment, the percentage of α4β7 + human T lymphocyte in engrafted human T cells was significantly decreased with anti-il7r mab. Moreover, histological analyses revealed that anti-il7r mab specifically prevented human T-cells infiltration and lesions in the gut. These results indicate that IL-7R blockade prevents specifically human T lymphocytes-mediated gut inflammation and modulates the level of α4β7 integrin expression. IL-7R blockade could offer novel therapeutic option in inflammatory bowel diseases.. Von Freeden-Jeffry, U., Vieira, P., Lucian, LA., McNeil, T., Burdach, SE., and Murray, R. (995). Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a non redundant cytokine. J. Exp. Med. 8 (4): Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S.I., and Nanan, R. (006). Expression of interleukin (IL)- and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 03, Totsuka, T., Kanai, T., Nemoto, Y., Makita, S., Okamoto, R., Tsuchiya, K., and Watanabe, M. (007). IL- 7 is essential for the development and the persistence of chronic colitis. J. Immunol. 78, BEY Karim PhD student 3rd year - UMR 703 PAnTher, INRA/ONIRIS, Nantes Intrathecal gene therapy using raav9-hsmn vector to treat moderate forms of SMA. Karim Bey*,, Johan Deniaud,, Carine Ciron,, Laurence Dubreil, Corinne Huchet 3, Philippe Moullier 4, Patrick Aubourg 5 and Marie-Anne Colle, INRA/ONIRIS UMR U703, Animal Pathophysiology and biotheraphy for muscle and nervous system diseases, Nantes, France. L UNAM University, Oniris, Nantes-Atlantic national college of veterinary medicine, food science and engineering, France. 3 INSERM UMR087/ CNRS UMR69, l Institut du Thorax, Nantes, France. 4 INSERM U089, Gene Therapy Laborotory, Nantes University, France 5 INSERM U986, Génomique, facteurs environnementaux et biothérapie des maladie endocriniennes et neurologiques, Université Paris Sud, Le Kremlin Bicêtre, France. Spinal muscular atrophy (SMA) the second most common autosomal recessive disorder causes of childhood mortality affecting between /6000 to /0000 live births. SMA is caused by deletion/mutations in the Survival Motor Neuron (SMN) gene. The disease is characterized by degeneration of spinal motor neurons (MNs), atrophy of skeletal muscles, and generalized weakness. SMA is clinically classified into four main types (I, II, III and IV) based on the age of onset and clinical severity. Currently, no curative treatment exists for SMA; type II/III SMA patients representing the majority currently awaiting treatment. Gene therapy, restoring SMN activity in MNs, is a promising therapeutic strategy for SMA. In the moderate forms (type II/III) of the disease, no lesion is found in peripheral organs. Thus, a targeted therapy directly into the CNS should be more appropriate. We have, recently, demonstrated that a single administration of an AAV9 vector into the cerebrospinal fluid leads to an efficient transduction of MNs in non-human primates. First, we have confirmed that our mouse model can mimick the human pathology of type-iii SMA. We have demonstrated a significant decrease in SMN protein level in whole spinal cord, brain and muscle. No loss of motor neurons has been shown at all observed time points. However, these mice display neurologic impairments as soon as 6 weeks as demonstrated with the hindlimb clasping reflex test, reflecting a defective neuronal transmission. Recent observations in muscle tissue from patients with SMA type II and III suggest abnormalities in the development and maturation of the neuromuscular junction. Then we have demonstrated that a single percutaneous lumbar intrathecal delivery of AAV vector using specific neuronal promoter can efficiently target MNs from proximal to distal part of the spinal cord in adult mouse. We are currently assessing this strategy using a therapeutic AAV9 vector delivered by lumbar puncture to restore SMN protein level in the CNS and to recover neurologic and motor functions in SMA mice. 8 CLOITRE Alexandra PhD student nd year - LIOAD, UMR INSERM 79, Nantes A potential role for interleukin 38 (IL-38) in periodontitis? CLOITRE Alexandra*, LAPERINE Olivier, GUICHEUX Jérôme, GEOFFROY Valérie, LESCLOUS Philippe. INSERM UMRS 79 Laboratoire d Ingénierie Ostéo-Articulaire et Dentaire «LIOAD» Groupe STEP «Skeletal Tissue Engineering and Physiopathology Periodontitis is a chronic inflammatory disease of bacterial origin that compromises the integrity of the tooth-supporting tissues. This disease is highly prevalent since a recent survey estimates that 47% of the US adult population is affected by periodontitis. Periodontitis is characterized by a progressive loss of the periodontal ligament and an uncontrolled alveolar bone resorption leading to teeth loss. In its severe form, periodontitis can also affect systemic health by increasing the patients risk and morbidity for atherosclerosis, rheumatoid arthritis or diabetes mellitus. It is acknowledged that the presence of bacterial species is necessary but probably not sufficient for the onset and progression of periodontitis. Dysregulations of host-mediated inflammatory response should be responsible of the severity and the morbidity of the disease in susceptible patients. The production of pro-inflammatory cytokines by immune cells, including IL-β, IL-6, and TNF-α seemed to play a role in this process because of their ability to increase the recruitment and activity of osteoclasts. Unfortunately, antibodies directed against these 3 cytokines have shown only partial beneficial effects on periodontitis thereby strongly suggesting that others mediators could be involved. It has been shown in vitro that IL-38, a new member of the IL- family, is an inhibitor of TH7 response, which has a key role in periodontitis pathogenesis. Our working hypothesis is that IL-38 could act as an inhibitor of inflammation in this disease. The objective of our work is to give new insights about involvement of IL-38 in periodontitis. We started investigating the expression of IL-38 in human gingival samples in healthy and affected patients. Our preliminary results by RT-qPCR showed that IL-38 expression tends to increase in patients with periodontitis. The potential role for IL-38 will also be studied in an animal model of periodontitis which is well handled in the laboratory. In vitro approaches in various cellular models of interest like primary keratinocytes, fibroblasts will be also performed. DAVID Benoit PhD student 3rd year UFIP UMR CNRS 686, Nantes Turning glycoside hydrolases into transglycosidases: a theoretical and experimental study of the internal water dynamics in the Thermus thermophilus β-glycosidase Benoît David *, Johann Hendrickx, Yves-Henri Sanejouand, Charles Tellier UFIP UMR-CNRS 686, Universite de Nantes, rue de la Houssinie re, 443 Nantes, France Mostly known for their ability to hydrolyse glycosidic linkages, numerous glycoside hydrolases are also able to catalyse reverse hydrolysis (transglycosylation) which can be harnessed for the synthesis of complex oligosaccharides. Although hydrolysis usually prevails over the reverse reaction, transglycosylation propensity has already been increased through mutagenesis and directed evolution experiments [, ]. However, little is known about the regulation of the balance between both activities. A previous experimental study on the β-glycosidase de Thermus thermophilus (Ttβgly) using deuterium exchange mass spectrometry has shown that amide hydrogens from a buried part of the protein were able to exchange with the solvent's [3]. The discovery via molecular dynamic (MD) simulation of a potential water channel connecting the bulk to the active site along this peptide has supported a possible role of internal water dynamics on the hydrolytic activity of Ttβgly [3]. 9 Mutagenesis of specific buried amino acid residues in the vicinity of this water channel coupled with the biochemical characterization of the corresponding mutants allowed to identify three specific residues involved in the regulation of the activity balance between hydrolysis and transglycosylation. Closing the end of the channel at the interface with the catalytic pocket, two of those residues may be involved in controlling water release from the core channel to the active site. Within this context, it is tempting to speculate that this particular water channel could be involved in supplying water mol
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