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Séminaire

  • Génomes

    • Vendredi 4 juin 10:00-11:00 - Arthur Talman - MIVEGEC (University of Montpellier-CNRS-IRD)

      Sex determination in malaria parasites

      Résumé : Malaria is caused by parasites of the genus Plasmodium. Whilst the disease is caused by asexual parasites, only sexual forms are capable of infecting mosquitoes. Sexual stages arise from a small subset of blood-stage parasites which divert from the cycle of asexual replication and embark on a sexual developmental trajectory. The bifurcation leading to a sexual fate is dependent on the master regulator of sex, the transcription factor AP2-G. In the absence of sex chromosomes or conserved sex-determining mechanisms, events that lead to determination into either a male or a female are completely unknown.
      We applied single cell technology to understand the cascade of transcriptional events leading to determination into one sex or the other in the rodent malaria parasite Plasmodium berghei. We performed a high throughput genome scale screen and identified genes involved in the sex determining pathway. We then characterised the role of one male determining factor in the human malaria parasite P. falciparum. We unravel the sex-specific regulation of md1 expression and initiate the functional characterisation of the sex determining pathway in human malaria parasites. Targeting sex determination to sterilise population of parasites in the host could be used as a strategy to interrupt transmission to mosquitoes.
      Contact : Joana SANTOS <joana.santos i2bc.paris-saclay.fr>

      Article

    • Vendredi 18 juin 11:00-12:00 - Arnaud Krebs - EMBL Heidelberg

      Cooperativity and antagonism at cis-regulatory elements

      Résumé : Cis-regulatory elements (CREs) control the expression of genes involved in the acquisition of cellular identity during development, and its maintenance in healthy tissues. CRE activation typically requires the binding of multiple TFs, yet the precise mechanisms underlying their coordinated action are largely unknown. TFs bind their target motifs in the context of chromatin, that carries information regulating their action. The impact of these epigenetic signals on the function of TFs at CREs is largely unknown.
      Current bulk assays used to map TF occupancy average binding events arising from millions of individual cells, not informing on the potential cooperativity and the antagonisms that organize their binding at CRE. To move beyond this boundary, we developed Single Molecule Footprinting (SMF) to quantify the binding of TFs at mouse regulatory regions. The method allows to simultaneously measure the occurrence of multiple TFs, nucleosomes and DNA methylation on individual molecules genome- wide. I will illustrate how we leveraged this new layer of information to understand mechanisms of TF cooperativity and the epigenetic regulation of TF binding at enhancers.
      Detecting multiple TF binding events on single DNA molecules has enabled us to determine TF co-binding frequencies in vivo. Systematic analysis of the co- occupancy patterns of thousands of TF pairs reveals widespread evidence of cooperative binding. It elucidates the binding cooperativity mechanism used by transcription factors in absence of strict organisation of their binding motifs, a characteristic feature of most of enhancers.
      Simultaneously quantification of DNA methylation and TF binding on individual DNA molecules allowed us to test if TF binding can occur at enhancers when their target DNA molecules are methylated in vivo. We identified a subset of cell type specific enhancers that showed reduced accessibility on methylated molecules, indicating a possible regulation of these loci by DNA methylation. Genetic perturbation experiments suggest a direct epigenetic control of TF binding at these loci.
      Relevant publications :
      Sönmezer, C, et al. Single molecule occupancy patterns of transcription factors reveal determinants of cooperative binding in vivo ; Molecular Cell. 2021.
      Krebs, AR, Studying transcription factor function in the genome at molecular resolution. Trends in Genetics. 2021
      Contact : GERARD Matthieu <Matthieu.GERARD cea.fr>

      Lieu : visio

      Article

  • Biologie Cellulaire

    • Vendredi 4 juin 11:00-12:00 - Aymeric BAILLY - CRBM Montpellier

      The Ubiquitin-like NEDD8 as a novel cellular stress signalling molecule.

      Résumé : Similarly to Ubiquitin, NEDD8 is activated and conjugated by a set of specialized enzymes (E1, E2 and E3) that covalently attach the NEDD8 molecule to its targets through a lysine residue. Although NEDD8 has been originally described for its role in regulating the Cullin-Ring-Ligase activities (CRL) through the modification of Cullins, recent advances established the existence of NEDD8 substrates beyond Cullins. Notably, we have found that NEDD8 can modify itself and form poly-NEDD8 chains that directly regulate HSP70 functions. I will present recent technological advances we have developped to identify novel NEDD8 E3 ligases.
      Contact : Renaud LEGOUIS <renaud.legouis i2bc.paris-saclay.fr>

      Lieu : Auditorium - bâtiment 21 - Gif ou visio

      Article

  • cytoskeleton club

    • Mardi 8 juin 11:30-13:00 - Logan Greibill - BIOCIL, Dpt Biologie Cellulaire, I2BC

      Cytoskeleton club

      Lieu : Webinar

      Article

Soutenance

  • Biologie Cellulaire

    • Vendredi 4 juin 14:00-17:00 - thesis defense Romane LEBOUTET - team Legouis, I2BC

      Functions of ubiquitin-like proteins GABARAP/LGG-1 during autophagy and development in Caenorhabditis elegans by CRISPR-CAS9 engineering

      Résumé : Autophagy is an important recycling process for the maintenance of cell homeostasis, allowing the recycling of cytoplasmic components. This mechanism is conserved among eukaryotes. In mammals, six homologs of atg8 exist (LC3A, LC3B, LC3C, GABARAP, GABARAPL1, GABARAPL2) and have multiple roles during this process, in the initiation, the recognition of cargo, the closure of autophagosomes and the fusion with the lytic compartment. These proteins exist in several forms, the precursor (form P) is cleaved into a cytosolic protein (form I) which, via a lipid conjugation system, is localized to the membrane (form II). Our research focuses on LGG-1, the homologue of the GABARAP family, essential for the viability and the development of the nematode Caenorhabditis elegans. In order to determine the different roles of GABARAP/LGG-1, we generated mutants by CRISPR/ CAS9, allowing expression of only the precursor, only the mature cytosolic form, or both. We were able to show that glycine116 of LGG-1 is essential for an efficient precursor cleavage and the localization of LGG-1 to autophagosome membranes. Our results show that a non-lipidable form of LGG-1 is sufficient to maintain both selective autophagy during the development (mitophagy and aggregation), and the physiological global autophagy during aging, or induced following a nutritional stress. Our results suggest that the major function of the mature cleaved form is involved in the early induction stages of the process.

      Lieu : Auditorium - building 21 - Gif-sur-Yvette or videoconference

      Article

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