September 2017
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Lundi 03/02/2020 Salle des Thèses CRC |
“Plant systems modelling” | |
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Lionel DUPUIS (Hutton Institute Dundee, UK)
Host: C. Godin
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Mardi 04/02/2020 Salle des Thèses CRC Colloquium au Centre Blaise Pascal |
« A maggot becomes a fly" : from cell dynamics to epithelial tissue patterning » | |
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Francois GRANER (Complex System and Matter, CNRS & Univ. de Paris-Diderot) hosted by Daniel Jost (LBMC) & Cerasela Calugaru (CBP & PSMN)
Development, homeostasis and regeneration of tissues result from a complex combination of genetics and mechanics. Our model system is the Drosophila metamorphosis, during which the fly strikingly changes, within a few days, from a rather simple maggot shape to a refined adult shape with wings, legs, antennas, waist, neck, and compound eye. |
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Mardi 05/02/2020 Salle des Thèses CRC |
« SIM-dependent SUMOylation of K595 together with unphosphorylated T592 is essential to render human SAMHD1 restriction-competent » | |
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Alessia Zamborlini (Université Paris Sud – France)
Hôte : renaud.mahieux@ens-lyon .fr
SAMHD1 is a cellular triphosphohydrolase (dNTPase) that inhibits HIV-1 replication in non-cycling immune cells by reducing the levels of cellular dNTPs below a threshold required for efficient reverse transcription. As SAMHD1 is ubiquitously expressed, the mechanisms underlying the regulation of its cell cycle-specific restriction activity has been deeply investigated in recent years. It is now well established that residue threonine (T) 592 of SAMHD1 is phosphorylated by cyclin/CDK complexes in a cell cycle-dependent manner, while it is hypo-phosphorylated in non-cycling cells refractory to HIV-1. The role of phosphorylation in the down-regulation of SAMHD1 antiviral functions is supported by finding that mutation of T592 into a phosphomimetic residue (D or E) abolishes restriction. However, the SAMHD1 T592D/E variant efficiently hydrolyzes dNTPs indicating that SAMHD1-mediated restriction may not exclusively rely on its dNTPase activity, and/or is regulation may not only depend on phosphorylation of T592.
We have established that inhibiting the SUMOylation process favors the infection of macrophages by HIV-1 and HIV-2∆Vpx, but not HIV-2. The existence of a correlation between the sensitivity to both small molecule inhibitors of SUMOylation and SAMHD1-dependent restriction led us to investigate whether the SUMO conjugation plays a direct role in the antiviral mechanism of this protein. We found that SAMHD1 harbors three major SUMO targeted sites (K469, K595 and 622) and a surface-exposed SIM. Functional studies revealed that blocking SUMO attachment to K595 is sufficient to humper the antiviral, but not dNTPase, function of SAMHD1. Importantly, mutation of the SIM precludes both viral restriction and K595 SUMOylation, strengthening the requirement of SUMO conjugation to this residue for the establishment of a SAMHD1-dependent antiviral state. We also investigated whether a connection exist between phosphorylation of T592 and SUMOylation of the adjacent K595 residue, and found that the two modifications occur independently of one another. Interestingly, we observed that SUMOylation-deficient K595A SAMHD1 variant is hypophosphorylated on residue T592, but is nevertheless antivirally inactive. In addition, we found that combining mutations disrupting K595 SUMOylation with the phosphoablative T592A change abolished SAMHD1-mediated restriction. In conclusion, our data demonstrate that SUMOylation of K595 and absence of T592 phosphorylation are prerequisites for SAMHD1 to be restriction competent. |
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Vendredi 07/02/2020 10H30 Salle des Thèses CRC Séminaire Externe |
« Polycomb proteins and 3D genome organization in developmental regulation » | |
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Giacomo CAVALLI (Institut de Génétique Humaine (IGH) à Montpellier ) hosted by Yad Ghavi-Helm
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Lundi 10/02/2020 11H00 Salle des Thèses CRC Séminaire externe |
« A role for the RNA modification m6A at the virus-host interface » | |
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Dr. Stacy HORNER (Lab Head at Duke University Medical Center Durham, NC – USA) The RNA modification N6-methyladenosine (m6A) plays an important role in the posttranscriptional control of eukaryotic mRNA fate and dynamically modulates important biological processes. We have previously found that m6A modification of viral RNA genomes regulates infection by RNA viruses in the Flaviviridae family. However, the function of epitranscriptomic m6A modification of cellular mRNA during viral infection is still unclear. Our work now reveals that infection by the Flaviviridae members dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV) similarly alters the m6A modification of a set of specific cellular transcripts without affecting the overall distribution of m6A across the epitranscriptome. We find that some of the observed changes in m6A modification are a result of innate immune sensing and ER stress, cellular pathways that are activated by Flaviviridae infection, suggesting that signal transduction from these pathways influences the specificity of the m6A methyltransferase complex. We then further elucidate how m6A regulates expression of these specific transcripts during Flaviviridae infection and how post-transcriptional control of these transcripts by m6A impacts viral infection. Taken together, these observations provide insights into how m6A modification of cellular transcripts is altered during viral infection and how this influences the outcome of Flaviviridae infection. |
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Lundi 10/02/2020 11H00 Salle des Thèses CRC Séminaire externe |
« Mechanisms and function of cell competition in health and disease » | |
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Eugenia PIDDINI (University of Bristol) hosted by François Leulier
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Vendredi 14/02/2020 11h Salle des Thèses CRC Séminaire externe |
« Quantitative fluorescence spectroscopy methods at the single cell level » | |
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Paolo ANNIBALE (Max Delbrück Center for Molecular Medicine in the Helmholtz Association – BERLIN)
Hosted by Olivier Gandrillon
Fluorescence microscopy methods can be employed to quantitatively monitor signaling within living cells. In particular, out of equilibrium fluctuations of the photon counts arising from diffusing fluorescently labeled molecules can be used to extract precise information on the dynamics as well as oligomerisation state of specific molecules. We will provide in this seminar a brief introduction to the biophysical foundation of these approaches before offering a tour over three state of the art applications: (i) Oligomerisation of G Protein Coupled Receptors, (ii) Quantification of non canonical amino acid labeling and (iii) dynamics of nuclear receptors at endogenous expression levels
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Jeudi 20/02/2020 10H30 Salle des Thèses CRC Séminaire externe
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« On the road to the nucleus of HIV-1 natural target cells » | |
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Francesca DI NUNZIO (CEA INSERM, Université Paris Saclay - FRANCE)
Contact : helene.dutartre@ens-lyon.fr
Retroviral replication proceeds through obligate integration of the viral DNA in the nucleus, essential for efficient viral gene expression. However, to be able to integrate into the host genome, the viral DNA must be led through the nuclear pore complex. Therefore, the morphology of the CA protein associated to the functional PIC during its translocation is completely unknown. We are currently studying early steps of viral life cycle in dividing and non-dividing cells, both target cells of HIV-1. Using breakthrough imaging technologies we deciphered the morphology adopted by HIV-1 during the translocation into the host nucleus of CD4+T cells. This step of the HIV-1 life cycle has never been previously elucidated because of the lack of appropriate technologies. Along with activated CD4+ T cells, macrophages are also natural target cells for HIV-1 and accumulating evidence points to a critical role of these cells in viral persistence, which remains a major roadblock to a cure for AIDS. Yet, it is not known whether the replication cycle proceeds differently in other cell types, such as non-dividing cells. Indeed, different cell types can exhibit widely divergent responses to viral attacks. Macrophages are terminally differentiated, non-dividing cells derived from blood monocytes, which play a critical role in the innate and adaptive immune response. Surprisingly, we detected in the nucleus of human macrophages viral RNA foci composed mostly of genomic, incoming RNA, which are niches of viral life cycle functions. These findings change our view of the spatiotemporal events of the early HIV-1 replication cycle in macrophages and may contribute to understand the mechanism underlying the persistence of HIV-1.
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Vendredi 21/02/2020 11h Salle des Thèses CRC Séminaire externe |
«Evolution and ecology of a Drosophila-Spiroplasma defensive symbiosis » | |
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Steve PERLMAN (University of Victoria, Canada)
Hosted by Benjamin Loppin
Multicellular organisms commonly harbour microbes that protect them against natural enemies, and these defensive symbionts are important players in host-parasite evolution and ecology. We have been studying a symbiosis between Drosophila flies and a maternally inherited bacterial endosymbiont called Spiroplasma that protects against infection by parasitic nematodes and parasitic wasps. Protection appears to involve
toxins called ribosome-inactivating proteins (RIPs). Spiroplasma genomes encode a diverse repertoire of RIP toxins, and we speculate that toxin diversity and evolution play an important role in specificity against different enemies. |
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Vendredi 24/02/2020 11h Salle des Thèses CRC |
“ Evolution of carnivorous traps from planar leaves” | |||
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Beatriz PINTO-GONCALVES ( JIC Norwich, UK)
Host: C. Scutt |
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