Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery

International audienc

A metabolic CRISPR-Cas9 screen in Chinese hamster ovary cells identifies glutamine-sensitive genes

Media and feed optimization have fueled many-fold improvements in mammalian biopharmaceutical production, but genome editing offers an emerging avenue for further enhancing cell metabolism and bioproduction. However, the complexity of metabolism, involving thousands of genes, makes it unclear which engineering strategies will result in desired traits. Here we present a comprehensive pooled CRISPR screen for CHO cell metabolism, including ~16,000 gRNAs against ~2500 metabolic enzymes and regulators. Using this screen, we identified a glutamine response network in CHO cells. Glutamine is particularly important since it is often over-fed to drive increased TCA cycle flux, but toxic ammonia may accumulate. With the screen we found one orphan glutamine-responsive gene with no clear connection to our network. Knockout of this novel and poorly characterized lipase, Abhd11, substantially increased growth in glutamine-free media by altering the regulation of the TCA cycle. Thus, the screen provides an invaluable targeted platform to comprehensively study genes involved in any metabolic trait, and elucidate novel regulators of metabolism

A metabolic CRISPR-Cas9 screen in Chinese hamster ovary cells identifies glutamine-sensitive genes

Media and feed optimization have fueled many-fold improvements in mammalian biopharmaceutical production, but genome editing offers an emerging avenue for further enhancing cell metabolism and bioproduction. However, the complexity of metabolism, involving thousands of genes, makes it unclear which engineering strategies will result in desired traits. Here we present a comprehensive pooled CRISPR screen for CHO cell metabolism, including ~16,000 gRNAs against ~2500 metabolic enzymes and regulators. Using this screen, we identified a glutamine response network in CHO cells. Glutamine is particularly important since it is often over-fed to drive increased TCA cycle flux, but toxic ammonia may accumulate. With the screen we found one orphan glutamine-responsive gene with no clear connection to our network. Knockout of this novel and poorly characterized lipase, Abhd11, substantially increased growth in glutamine-free media by altering the regulation of the TCA cycle. Thus, the screen provides an invaluable targeted platform to comprehensively study genes involved in any metabolic trait, and elucidate novel regulators of metabolism

Revues modernistes, revues engagées

Revues modernistes ou revues d’avant-garde ? On oppose souvent les termes « modernisme » et « avant-garde » : le « modernisme » serait une révolution essentiellement littéraire et artistique, sans efficacité au-dehors des murs de l’atelier ou de l’univers restreint des littérateurs ; à l’inverse, l’« avant-garde » constituerait un modernisme politisé, qui s’attaque à l’institution de l’art et vise à transformer ses rapports avec la vie et la société. Le terme d’avant-garde est employé surtout à propos de groupes dont l’agitation a été bruyante ou a su, un temps, se greffer sur des partis révolutionnaires : futurismes en Italie et en Russie, dada et surréalisme en France. Le terme de modernisme, en revanche, est plutôt employé dans l’univers anglo-américain pour désigner des auteurs canoniques et élitistes (Joyce, Eliot, Pound et quelques autres), sous l’influence d’une tradition critique (le new criticism) qui a longtemps cherché à gommer le caractère collectif et la puissance contestataire de cette production littéraire. Guide international des revues modernistes et réflexion sur cet enjeu central de la critique contemporaine, cet ouvrage dépasse l’opposition entre avant-garde et modernisme, pour montrer des hommes et des femmes, à l’œuvre dans un monde dont ils perçoivent les difficultés autant que les beautés. Champ d’expérimentation et champ de bataille, les revues modernistes sont ouvertes à toutes les polémiques