Publisher Correction: Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Max-Planck-Gesellschaft (Max Planck Society); doi: https://doi.org/10.13039/50110000418

Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Max-Planck-Gesellschaft (Max Planck Society); doi: https://doi.org/10.13039/501100004189Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5-/- HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence

Investigation métabolique des mycoplasmes dans le tractus respiratoire des cochons

In this PhD thesis, we presented three main types of analyses of metabolism, and in most cases involving symbiosis: metabolic dialogue between a trypanosomatid and its symbiont, comparative analyses of metabolic networks and exploration of metabolomics data. The respiratory tract of swines is colonized by several pathogenic bacteria, among which are three mycoplasma species: Mycoplasma flocculare, Mycoplasma hyopneumoniae, and Mycoplasma hyorhinis. In this work, we created whole-genome metabolic network reconstructions for all sequenced strains from these three Mycoplasma species. Similar to other Mycoplasma models all reconstructed networks exhibit low connectivity due to the simplicity of the biological model. We were able to show that the three swine mycoplasma species have similar metabolic capabilities. Interesting metabolic differences include the myo-inositol catabolism and a more complete system for glycerol uptake in M. hyopneumoniae and a wide range of carbohydrate uptake in M. hyorhinis. Glycerol conversion to DHAP, a missing activity only in M. flocculare, produces toxic hydrogen peroxide and may explain the lack of pathogenicity of this species. The uptake of a wider range of carbon sources in M. hyorhinis may also explain why this species is a wide-known contaminant in cell cultures. Growth experiments showed that defined media described for other Mycoplasma species are not suitable for the growth of respiratory tract swine mycoplasmas and that peptone is essential for the maintenance of cell viability of both M. hyopneumoniae and M. flocculare in defined media. Metabolomic data suggests that even though these species are extremely similar from a genomic and metabolic point of views, the products and reaction rates differ and gene regulation may interfere directly in metabolism. This, in turn, may account for many aspects still unknown that influence directly different levels of pathogenicity in each of themL'appareil respiratoire des porcs est colonisé par plusieurs bactéries, parmi lesquelles trois espèces de mycoplasmes : Mycoplasma flocculare, Mycoplasma hyopneumoniae et Mycoplasma hyorhinis. Lors de ce doctorat, notre principal objectif était de mieux comprendre le métabolisme différentiel dans chacune des espèces à l'aide de différentes approches. Nous avons reconstruit les réseaux métaboliques complets pour toutes les souches séquencées de ces trois espèces de mycoplasmes afin d'y détecter des caractéristiques distinctes. Nous avons pu montrer que, bien que les trois espèces de mycoplasmes du porc ont des capacités métaboliques semblables, certaines différences existent qui incluent, d'une part, le catabolisme de myo-inositol et un système plus complet pour l'absorption du glycérol, et d'autre part, une large gamme de moyens d'absorption de carbohydrates chez M. hyorhinis. L'utilisation de glycérol comme source de carbone, une activité qui est absente uniquement dans M. flocculare, produit du peroxyde d'hydrogène qui est toxique, ce qui peut expliquer l'absence de pathogénicité de cette espèce. L'absorption d'un plus large éventail de sources de carbone chez M. hyorhinis peut également expliquer pourquoi cette espèce est un contaminant largement connu des cultures cellulaires. Des expériences de croissance ont montré que les milieux définis décrits pour d'autres espèces de mycoplasmes ne sont pas appropriés pour la croissance de mycoplasmes du tractues respiratoire de porcs, et que la peptone est essentielle pour le maintien de la viabilité des cellules à la fois de M. hyopneumoniae et de M. flocculare dans des milieux définis. Dans ce travail, nous proposons également de nouveaux média définis qui, in silico, sont extrêmement appropriés pour les mycoplasmes du porc. Les données de métabolomique suggèrent que même si ces espèces sont extrêmement similaires du point de vue de leurs génomes et des métabolismes, les produits et les taux de réaction diffèrent et la régulation des gènes peuvent interférer directement dans le métabolisme. Pour expliquer ces différences ainsi que d'autres décrits dans la littérature qui suggèrent que certains types de régulation de l'expression du gène existent en effet dans ces espèces, nous avons également essayé de recueillir des informations sur de nouvelles séquences promotrices. Ainsi, cette thèse servira de base pour l'étude du métabolisme différentiel et des pathologies causées par les mycoplasmes du tractus respiratoire du porc et pourra aider à proposer des façons de prévenir à l'avenir le développement des maladies associée

Investigating the Human Host—ssRNA Virus Interaction Landscape Using the SMEAGOL Toolbox

Viruses have evolved numerous mechanisms to exploit the molecular machinery of their host cells, including the broad spectrum of host RNA-binding proteins (RBPs). However, the RBP interactomes of most viruses are largely unknown. To shed light on the interaction landscape of RNA viruses with human host cell RBPs, we have analysed 197 single-stranded RNA (ssRNA) viral genome sequences and found that the majority of ssRNA virus genomes are significantly enriched or depleted in motifs for specific human RBPs, suggesting selection pressure on these interactions. To facilitate tailored investigations and the analysis of genomes sequenced in future, we have released our methodology as a fast and user-friendly computational toolbox named SMEAGOL. Our resources will contribute to future studies of specific ssRNA virus—host cell interactions and support the identification of antiviral drug targets.publishe

High-throughput genomics and transcriptomics to decipher host-symbiont molecular dialogue in the cereal weevil Sitophilus oryzae andSodalis pierantonius endosymbiotic association

International audienc

High-throughput genomics and transcriptomics to decipher host-symbiont molecular dialogue in the cereal weevil Sitophilus oryzae andSodalis pierantonius endosymbiotic association

International audienc

Spatial and morphological reorganization of endosymbiosis during metamorphosis accommodates adult metabolic requirements in a weevil

International audienc

European commitment to COP21 and the role of energy consumption, FDI, trade and economic complexity in sustaining economic growth

The nexus between economic growth and energy consumption has been exhaustively explored, yet the empirical evidence and the theoretical points of view remain at odds. This study contextualises and capitalises on this discrepancy and examines the connection between non-renewable and renewable energy consumption and economic growth, considering the moderating impact of economic complexity, trade openness, FDI and institutional quality. We use a panel quantile regression model and data from 32 European countries in the period 1995–2014. Our key results show that economic complexity, renewable energy consumption, trade openness, FDI and institutional quality enhance economic growth. The results for non-renewable energy consumption showed both a positive and a negative impact in different quantiles, indicating that the consumption of renewable energy is in fact more effective for economic growth than the use of non-renewables. Our findings have far-reaching implications for stakeholders and policymakers working on sustainable economic growth and energy policy with a view to meeting the commitments made under the Paris Agreement (COP21)