Source DB | nl |
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Institution | UGent |
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Code | 12c5a49a-fcf1-4a0e-86fb-7feeb4ee947b |
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Unit | 85720305-a223-4aad-b6b6-5422ac5c0867
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Begin | 1/1/2019 |
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End | 12/31/2022 |
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title fr |
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title nl | Functie en biogenese van subpopulaties van extracellulaire vesikels in kanker
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title en | Function and biogenesis of extracellular vesicle subsets in cancer
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Description fr |
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Description nl | Extracellular vesicles (EV) are polydisperse nanometer-sized membraneous structures containingproteins, nucleic acids and metabolites. Their secretion is tightly regulated through RabGTPase/effector complexes, including Rab27b-melanophilin (Mlph) and viral Gag-like proteins,including arrestin domain containing protein-1 (Arrdc1). We will use state-of-the-art density and sizebased AF4 fractionation technology to isolate monodisperse EV populations. Molecular signaturesof each monodisperse population will be achieved through U+2013omics approaches. Preliminaryevidence suggests the existence of small and larger EV, of which the larger EV are uniquely positivefor Rab27b-Mlph and Arrdc1; in contrast small EV do not contain Rab27b-Mlph. Geneticinterference with Mlph expression in hormone-sensitive breast cancer cells induces DNA doublestrand breaks and cell death. Recent reports indicate the importance of regulated EV release tocontrol cytosolic double stranded dsDNA levels to avoid type I interferon induced cell death. Usingloss of function point mutations and genetic interference we will investigate whetherArrdc1/Rab27b/Mlph are differentially crucial to dispose cytosolic dsDNA through secretion of EV.We will scrutinize the functional consequences of this cellular disposal mechanism using impedanceand image based real time monitoring of hormone sensitive breast cancer cell lines and throughorthotopic mouse models to investigate breast cancer metastasis.
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Description en | Extracellular vesicles (EV) are polydisperse nanometer-sized membraneous structures containingproteins, nucleic acids and metabolites. Their secretion is tightly regulated through RabGTPase/effector complexes, including Rab27b-melanophilin (Mlph) and viral Gag-like proteins,including arrestin domain containing protein-1 (Arrdc1). We will use state-of-the-art density and sizebased AF4 fractionation technology to isolate monodisperse EV populations. Molecular signaturesof each monodisperse population will be achieved through U+2013omics approaches. Preliminaryevidence suggests the existence of small and larger EV, of which the larger EV are uniquely positivefor Rab27b-Mlph and Arrdc1; in contrast small EV do not contain Rab27b-Mlph. Geneticinterference with Mlph expression in hormone-sensitive breast cancer cells induces DNA doublestrand breaks and cell death. Recent reports indicate the importance of regulated EV release tocontrol cytosolic double stranded dsDNA levels to avoid type I interferon induced cell death. Usingloss of function point mutations and genetic interference we will investigate whetherArrdc1/Rab27b/Mlph are differentially crucial to dispose cytosolic dsDNA through secretion of EV.We will scrutinize the functional consequences of this cellular disposal mechanism using impedanceand image based real time monitoring of hormone sensitive breast cancer cell lines and throughorthotopic mouse models to investigate breast cancer metastasis.
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Qualifiers | - cancer - kanker - |
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Personal | De Wever Olivier, Hendrix An |
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Collaborations | |
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