Objective Mucopolysaccharidosis-VI (MPS-VI) is a lysosomal storage disorder predominantly affecting skeletal remodelling and caused by pathogenic mutations in the ARSB gene, encoding the glycosaminoglycan-degrading enzyme arylsulfatase B. Preliminary analysis of Arsb-deficient mice unraveled a skeletal phenotype of similar severity and with lysosomal storage defects in different skeletal cell types. This Arsb-deficient mouse model therefore provides an excellent tool to understand the skeletal and non-skeletal pathologies related to MPS-VI and to address the clinically relevant question, if enzyme replacement therapy (ERT) can influence the existing (non-)skeletal pathologies in lysosomal storage disorders. Moreover, another major objective is to unravel the cellular consequences of Arsb-deficiency on a molecular level and to investigate mechanisms of ARSB uptake and lysosomal delivery in different primary cell types of Arsb-deficient mice. This project will therefore certainly generate knowledge with relevance for other (skeletal) disorders as well, as the cellular defects in MPS-VI are closely linked to that of two of the most prevalent disorders in the European Union, i.e. osteoporosis and osteoarthritis. Next to its scientific goals, this proposal aims to offer a broad personal training program for me as a postdoctoral researcher as well. Handling this project will not only offer an intensive scientific training (intellectual-methodological), but also improve my skills regarding project management (administrative-financial) and writing. As a two-way transfer, my previously acquired knowledge on the genetics of skeletal disorders and related experimental skills will be transferred to the host organization. A final goal of this proposal is to disseminate the acquired data towards specialized scientific audiences (scientific conferences and publications) and propagate these data towards non-expert audiences (patient meetings, press releases) as well. Fields of science natural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Net EU contribution € 159 460,80 Address Martinistrasse 52 20251 Hamburg Germany See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 159 460,80
