Vendredi
02/02/2018
11h

Salle des Thèses Chantal Rabourdin-Combe

Charlotte RIVIERE (ILM (Institut Lumière Matière), UMR CNRS 5306,Biopphysic team)

Many drug candidates for cancer treatment show potential when examined in-vitro but fail in clinical trials. This failure may stem at least in part from the use of conventional in-vitro systems that fail to replicate the physiological microenvironment in humans as well as the lack of cell-phenotypic measurements. In addition, there are now number of evidences that mechanics is playing an important role in the malignant transformation of cells during tumor progression and dissemination. In the biophysic group, we try to tackle these important issues (micro-environment and mechanics) by developing original techniques enabling to precisely control cell micro-environment, including the applied mechanical stress. The aim is to design in vitro assays reproducing as much as possible the environment encountered by tumor cells in vivo and to provide quantitative parameter of cell dynamic behavior that can be used as novel read-outs of cancer stage. Using time-lapse microscopy and cell tracking, as well as Traction Force Microscopy, such phenotyping cell
characterization is performed at various stages of the metastatic progress: (1) Initial Tumor growth, (2) Cancer Stem cells Niche (3) Metastatic cells invasion, and (4) Metastatic cells extravasation. The final aim is to provide complementary approaches and quantification of cancer cells drug resistance in in-vivo like environment.

Lundi
05/02/2018
11h00

Salle des Thèses Chantal Rabourdin-Combe

Benjamin LOPPIN (Laboratoire de Biométrie et Biologie Évolutive, Lyon)

Jeudi
08/02/2018
12h15

Salle des Thèses Chantal Rabourdin-Combe

Pierre-Antoine DEFOSSEZ (Centre Epigénétique et Destin Cellulaire, Université Paris Diderot)

Contact : kiran.padmanabhan@ens-lyon.fr

DNA methylation is an essential epigenetic mark in mammals: it controls the expression of imprinted genes, germline genes, transposons, and is intimately linked to the local chromatin state. For all these reasons, the maintenance of correct patterns of DNA methylation is essential for the survival of mammalian cells. This pattern has to be re-established at each round of DNA replication. One of the key actors in this process is the protein UHRF1: it is essential for DNA remethylation after replication, but its mode of action is unclear. We have characterized the UHRF1 interactome by proteomics and found that DNA Ligase 1 (LIG1) is a highly abundant interactor of UHRF1. We have mapped the interaction domains and found that a Tudor domain of UHRF1 interacts with an H3-like histone mimic within LIG1. We show that the interaction requires the methylation of the LIG1 histone mimic by the lysine methyltransferases G9a or GLP. Finally, we find that the interaction with LIG1 promotes the recruitment of UHRF1 to sites of DNA replication and is required for normal DNA remethylation. These results prompt a reinterpretation of the function of UHRF1's Tudor domain, which we show can bind non-histone proteins. They also reveal a new level of complexity in DNA Ligase 1, identify a new non-histone target of G9a and GLP, and provide the first example of a histone mimic that coordinates DNA replication and DNA remethylation.

Mardi
13/02/2018
11h00

Salle des Thèses Chantal Rabourdin-Combe

Pr. Volker LOHMANN University of Heidelberg, Heidelberg – ALLEMAGNE)

Contact : marlene.dreux@ens-lyon.fr

Hepatitis C virus (HCV) infections most often result in chronic outcomes, although the virus constantly produces replication intermediates, in particular double-stranded RNA (dsRNA), representing potent inducers of innate immunity. We have characterized the fate of HCV-derived replication intermediates in hepatocyte cultures to understand the mechanisms contributing to viral persistence in presence of an active innate immune response.  Our results indicate that part of the HCV dsRNA intermediates are released from infected cells in extracellular vesicles attenuating activation of TLR3 in HCV-infected cells. This mechanism represents a novel strategy to dampen intracellular innate immune responses, potentially contributing to the establishment of persistence.

Lundi 23/02/2018
11h

Salle des Thèses Chantal Rabourdin-Combe

Michel WASSEF   (Institut Curie)

Lundi
26/02/2018
11h

Salle des Thèses Chantal Rabourdin-Combe

Ehab ABOUHEIF  (McGill University)

Mercredi 28/02/2018
11h

Amphi Pasteur - Tour Inserm CERVI *

David BOUTBOUL (hôpital Saint Louis)

Contact : NICOLAS, Jean-Francois

Ikaros est un facteur de transcription hématopoïétique codé par le gène IKZF1 et impliqué dans la différenciation myéloïde et lymphoïde et dans le contrôle de la prolifération cellulaire. Des mutations somatiques perte de fonction d'Ikaros ont été décrites au cours des leucémies aiguës lymphoblastiques B de l'enfant et sont associées à un pronostic péjoratif. Plus récemment, des mutations germinales hétérozygotes perte de fonction ont été rapportées chez des patients présentant un déficit lymphoïde B et un sur-risque de leucémie aiguë. Nous avons mis en évidence de nouvelles mutations germinales d'Ikaros chez 7 patients présentant cette fois-ci une déficit cellulaire T sévère responsable d'infections opportunistes précoces. Nous avons pu montrer que ces nouvelles mutations impactaient la prolifération lymphocytaire T ainsi que le développement de cellules présentatrices d'antigène comme les cellules dendritiques. A la différence des mutations précédemment décrites responsables d'une haplo-insuffisance, ces mutations exercent un effet dominant négatif.