Rechercher






Nos tutelles

CNRS

Nos partenaires


Accueil

18 juin 2019: 2 événements

  • Département Microbiologie

    Mardi 18 juin 11:30-12:30 - Véronique Fontaine - Université Libre de Bruxelles

    Looking for mycobacterial GroEL1 functions

    Résumé : Tuberculosis is a disease with high morbidity and mortality rates in the world, caused by slow-growing mycobacteria, mainly Mycobacterium tuberculosis. The chaperone GroEL1, also known as Cpn60.1, was recently shown to play a key role in several mycobacterial functions, including persistency in the host, bacterial virulence, and even antimicrobial resistance. Although the molecular mechanisms of action of this protein are multiple, and still not totally elucidated, GroEL1 interaction with metallic ions and lipids is further puzzling the picture.

    Lieu : Salle Kalogeropoulos - Bât. 400, Campus d’Orsay

    En savoir plus : Département Microbiologie
  • Département Virologie

    Mardi 18 juin 14:00-15:00 - Emiliano RICCI - Laboratoire de Biologie et Modélisation de la Cellule, ENS Lyon

    Global impact of translation on mRNA stability in T cells and macrophages and a potential role for UTRs in its modulation

    Résumé : Post-transcriptional control is crucial for regulating protein expression, both basally and in response to extracellular cues. Proper signal transduction requires tight control of both response induction and termination. While much work has gone into understanding how mRNAs are translationally upregulated to boost protein expression during signaling, much less is known about how such responses are terminated. One way protein expression might be attenuated following translational activation is by targeting mRNAs to translation-dependent degradation (TDD), thus making any increase in protein expression self-limiting. The extent to which TDD is a general mechanism for limiting protein expression is currently unknown.
    Here we describe a comprehensive analysis of basal and signal-dependent gene expression in primary mouse T cells and macrophages. In order to measure the impact of TDD in regulating gene expression, we performed RNA-Seq, PAS-Seq and ribosome profiling to monitor RNA levels, 3’UTR length, translational efficiency, and RNA degradation transcriptome-wide, both before and after activation of T cells and macrophages. Our data surprisingly indicate that most unstable mRNAs are decayed to some extent in a translation-dependent manner, both in resting and activated cells. Interestingly, the extent of TDD is inversely correlated to the length of the 5’UTR and 3’UTR but not to that of the coding sequence. Furthermore, ribosome density also appears to explain the extend of TDD but in a biphasic manner. These unexpected observations highlight the strong interconnection that exists between mRNA translation and untranslated regions in regulating mRNA decay.

    Lieu : Salle de réunion - bâtiment 14 - campus de Gif-sur-Yvette

    En savoir plus : Département Virologie

18 juin 2019: 2 événements

  • Département Biochimie, Biophysique et Biologie Structurale

    Mardi 18 juin 10:00-12:00 - Agathe Urvoas - I2BC - Equipe Modélisation et Ingénierie des Protéines

    Ingénierie par évolution dirigée d’une famille de protéines artificielles à motifs structuraux répétés : les alphaReps - conception, caractérisation et applications

    Résumé : L’ingénierie d’ossatures protéiques par des approches d’évolution dirigée permet d’obtenir de nouvelles structures protéiques fixant spécifiquement des molécules cibles choisies. Une famille de protéines artificielles à motifs structuraux répétés, nommées αRep a été développée. Les αReps sont des protéines particulièrement stables et faciles à produire sous forme recombinante en comparaison avec les protéines dérivées d’anticorps classiquement utilisées. A partir d’une banque comportant plus d’un milliard de variants, il est possible de sélectionner des αReps fixant spécifiquement, à haute affinité (KD de l’ordre du nM au μM) des cibles protéiques d’intérêt. Les applications de ces protéines artificielles ont été explorées : en biochimie structurale pour aider à la cristallogenèse, en biologie cellulaire pour le développement de traceurs intracellulaires ou pour le développement de biosenseurs génériques, en chimie avec la conception de métalloenzymes artificielles par couplage de complexes organométalliques mais également en physique pour la reconnaissance de surfaces non biologiques et la morphosynthèse de nanoparticules.
    La modularité des αReps assimilables à des briques de Lego® moléculaire ouvre la voie à des constructions combinatoires pouvant conduire par exemple à l’ingénierie de voies métaboliques artificielles, à des assemblages protéiques fonctionnalisés ou encore à des outils d’interaction allostériques.

    Lieu : Salle Edgar Lederer - Bât. 430, Campus d’Orsay

    En savoir plus : Département Biochimie, Biophysique et Biologie Structurale
  • Département Biologie Cellulaire

    Mardi 18 juin 14:00-17:00 - Amanda Martin Barranco - I2BC, équipe Approches Intégratives du Transport des Ions

    Role of the protein HIR2 and the Plasma membrane microdomains in the control of Fe acquisition, using Arabidopsis thaliana as a model plant

    Résumé : Iron is an essential nutrient for plant growth and development. In Arabidopsis thaliana, the transporter IRT1, which allows iron absorption through the epidermic cells of the root, is a major actor in iron nutrition. Despite of it, IRT1 also transports the non-iron metals zinc (Zn), manganese (Mn) and cobalt (Co). These metals are considered as the secondary substrates of IRT1, and therefore this transporter is considered as poorly specific. Our laboratory has recently uncover that these secondary substrates regulate IRT1 endocytosis. In order to uncover the different proteins that can be implicated in the traffic or in the regulation of IRT1 activity, we have proceeded to perform IRT1 immnopurifications, followed by mass spectrometry analyses. This approach has allowed us to produce a first interactome list of IRT1. Among the proteins that interact with IRT1, we have isolated AHA2 and FRO2, both well known in the process of iron acquisition in Arabidopsis, and also a SPFH domain containing protein known as HIR2. Although it is known that HIR2 is contained in membrane microdomains in Arabidopsis, its function is still to determine. Nevertheless, in the animal kingdom, SPFH domain containing proteins have been proposed as implicated in the formation of membrane microdomains. This is specially the case of the specific SPFH domain containing proteins known as Flotillins, which have the ability to mediate endocytosis in animals as in plants.
    After validation of the interaction between IRT1 and FRO2/AHA2/HIR2 by different complementary approaches, we have microscopically analyzed the intracellular dynamics of these proteins. Our results suggest the existence of a protein complex that reunites the three major actors of iron homeostasis in Arabidopsis : IRT1, FRO2 and AHA2. We suspect that the main function of this complex is to optimize the process of iron absorption in the root. In spite of what is known for IRT1 and despite being part of a same complex, FRO2 and AHA2 are not massively endocytosed in response to a non-iron metal excess (Zn, Mn, Co). Furthermore, we have shown that FRO2 and AHA2 are ubiquitinated, although their ubiquitination is also independent of the concentration of the non-iron metals, unlike the ubiquitination of IRT1. Finally, using reverse genetic approaches, we have been able to show that HIR2 is implicated in the maintenance of the iron homeostasis. Indeed, hir2 mutants are extremely sensitive to lack of Fe, even though they present posttranslational deregulations that result in the an overaccumulation of the protein IRT1. We are currently trying to determine how HIR2 regulates the dynamics and/or the stability of IRT1 inside the cell. HIR2 could be assuring the recruiting of IRT1,or the recruitment of the whole iron acquisition complex, into specific membrane microdomains. On the other hand, HIR2 could be implicated in a new pathway of internalization of IRT1, independent of clathrin.

    Lieu : Auditorium I2BC - Bât. 21, Campus de Gif-sur-Yvette

    En savoir plus : Département Biologie Cellulaire