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Theses

Obésité et troubles du contrôle postural rôles de certaines contraintes morphologiques et sensori-motrices

Abstract : ALK1 is a TGF-β family receptor, mainly expressed on endothelial cells. The physiologic and circulating ligand of ALK1, BMP9, was discovered by our laboratory in 2007, which opened opportunities for studying the function of ALK1. The first part of my thesis was on the functional analysis of ALK1 mutants from HHT-2 patients in response to BMP9. This study allowed us to: 1) propose functional haploinsufficiency as a model for HHT-2; 2) develop a diagnostic tool to discriminate pathogenic mutations from rare polymorphisms, based on their BMP9 response; 3) increase our knowledge of important amino acids in ALK1 for the BMP9 response. A second work was on the production of the mature form of BMP9 and of the extracellular domain of ALK1 in order to study the crystallographic structure of the complex. The expression of these proteins and their purification are in optimization phase. Lastly, a third project was on the analysis of the role of BMP9 in angiogenesis in vivo. Neutralization of BMP9 using two strategies induces an increase of the vascular density of the retina in mouse. Mechanism of action is under investigation.
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Submitted on : Thursday, December 1, 2011 - 9:47:38 AM
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Jean-Baptiste Mignardot. Obésité et troubles du contrôle postural rôles de certaines contraintes morphologiques et sensori-motrices. Médecine humaine et pathologie. Université de Grenoble, 2011. Français. ⟨NNT : 2011GRENS021⟩. ⟨tel-00646963⟩

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