Objective
The hereditary spastic paraplegias (HSPs) are a group of neurodegenerative conditions characterised by the degeneration of longer spinal cord motor tract axons. The normal function of the 13 cloned spastic paraplegia genes (SPGs) is largely unknown, but most encode intracellular membrane-associated proteins. Recently, the host laboratory has established that one of these genes, SPG6, encodes an endosomal regulator of BMP receptor trafficking, and regulates synaptic growth and axonal microtubules via this effect. The aim of this project is to test whether other intracellular membrane SPG products also function in receptor membrane trafficking and signalling, particularly in the BMP pathway. The focus of the study will be on the three SPGs currently most amenable to study in Drosophila melanogaster, a model system with proven power in this area. Top priority will be given to the recently identified spastizin (SPG15), an endosomal localised protein containing a FYVE motif, found on proteins that function in the regulation of endocytic trafficking. Mutants of the Drosophila SPG15 homologue will be generated to study phenotypes, particularly at the neuromuscular junction (NMJ). Also, antibodies will be generated to investigate spastizin colocalisation and association with BMP, Wnt, and Notch pathway subunits. In addition, I will use similar approaches to test two other membrane associated SPG products: spastin (SPG4) and atlastin (SPG3A). These are among the most commonly mutated SPGs, thus Drosophila stocks and reagents are already available, but their potential role in regulating endosomal trafficking pathways is not well studied. This investigation, into the functional pathways of spastizin, spastin, and atlastin, will further the understanding of the mechanism of action of mutated proteins in motor neuron degeneration.
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
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-IEF-2008
See other projects for this call
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.
Coordinator
CB2 1TN CAMBRIDGE
United Kingdom
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.