Objective
Lysosomal storage diseases (LSD) are a group of ~ 50 genetic disorders, which mainly affect children. LSDs are clinically heterogeneous but are frequently dominated by progressive neurologic deterioration. Most patients pass away after years of lingering illness. In general, the molecular pathogenesis of LSDs is still poorly understood. To gain insight into disease mechanisms the project investigates cellular proteomic alterations sequentially induced by increasing lysosomal storage. In vivo and in vitro models of selected LSDs affecting the nervous system will be investigated. Whole cell proteomes, subcellular fractions and tissues will be analyzed using quantitative large scale mass spectrometry based proteomic techniques employing stable isotope labeling based multiplex quantification approaches (TMT, iTRAQ, SILAC) and tandem mass spectrometry on an Orbitrap Velos mass spectrometer.
Three model systems focusing on glial and neuronal cells will be analyzed: a) in vitro differentiation of NG2 glia to oligodendrocytes under normal or sulfatide accumulating conditions as a model for metachromatic leukodystrophy (MLD); b) in vivo alterations occurring in the course of progressive demyelination in the peripheral nervous system of a mouse model of MLD c) a cell culture model in which consequences of increasing storage of ß-glucosylceramide in neurons will be examined as a model of Gaucher disease.
Using the quantitative data, alterations in protein expression and phosphorylation will be identified, grouped and analyzed for up- and downstream interaction partners as well as biological processes they are involved in. This will be done for various levels of storage to understand the succession and possibly the hierarchy of events. These data will allow describing cellular consequences of lysosomal storage in a so far unprecedented way, will allow generating new working hypotheses, and may provide the basis for the identification of new therapeutic targets.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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-2012-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
53127 BONN
Germany
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.