Objective
"Lysosomal storage disorders (LSDs) are inherited diseases characterized by progressive intracellular accumulation of undigested macromolecules due to lysosomal dysfunction. This results in a complex phenotype with broad pathological manifestations. Most LSDs are characterized by defective skeletogenesis. Despite this, the mechanisms by which lysosomal storage affects skeletal development and function is still unknown and the efficacy of current therapies on the skeletal system is limited. This project aims at identifying the molecular mechanisms that underlye the skeletal abnormalities in LSDs and to develop novel therapeutic strategies directed toward these defects. In recent years, the lysosome has emerged as a key signaling centre, which regulates and is in turn regulated by the activity of signaling molecules. By using the Mucopolysaccharidosis VII (MPSVII) and the Multiple Sulfatase Deficiency (MSD) mouse as models of LSD, we plan to characterize the consequences of lysosomal dysfunction on major signaling pathways involved in skeletogenesis, and to identify tools and pathways that prevent accumulation and/or promote clearance of storage in bone cells. Once identified, the molecular players in these signaling pathways are appealing therapeutic targets for the treatment of the skeletal phenotype in LSD.
The enhancement of lysosomal function can promote “cellular clearance” in cells affected by lysosomal storage even without correcting the underlying genetic defect. Supported by strong preliminary data, we will use genetic and pharmacological manipulation of TFEB, the master transcription factor that regulates lysosomal biogenesis, as a tool to promote clearance and in turn rescue the skeletal abnormalities of LSDs. In summary, this project aims to identify the pathogenetic mechanisms underlying the skeletal manifestation of lysosomal storage disorders and to provide proof-of-principle that these skeletal features can be treated."
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
00185 ROMA
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.