Objective
Our understanding of Parkinson’s disease (PD) pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic, most frequent, form of PD. It may be possible to overcome these challenges by reprogramming somatic cells from patients into induced pluripotent stem cells (iPSC). In preliminary studies, we have generated a collection of 50 iPSC lines representing both sporadic PD and familial PD patients, and identified distinct PD-related neurodegeneration phenotypes arising, upon long-term culture, in DAn differentiated from these PD-iPSC. Here, I propose to take advantage of this genuinely human PD model to investigate: i) mechanistic insights responsible for the PD phenotype identified in our model (by combining molecular and biochemical analyses to study mitochondrial function and redox profile, as well as genome-wide transcriptional profile of control versus PD-patient specific iPSC-derived DAn); ii) early functional alterations in patient-specific iPSC-derived DAn, which would predate neurodegeneration signs and provide valuable information as to ways to prevent, rather than rescue, neurodegeneration in PD patients (by electrophysiological recordings in in vitro reconstructed neuronal/glial networks to assess synaptic dynamics together with neuronal excitability); iii) further refinements in our iPSC-based PD model, including the generation of iPSC lines representing asymptomatic patients carrying pathogenic mutations, and the correction of known mutations by gene edition, all of which will allow exploring the relationship between pathogenic mutations and the genetic makeup of patients; and iv) whether DAn degeneration in PD is solely a cell-autonomous phenomenon, or whether it is influenced by an altered cross-talk between DAn and glial cells. These studies may impact significantly on our understanding of PD pathogenesis and on the development of new therapy strategy.
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
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology parkinson
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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.
ERC-2012-StG_20111109
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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.
Host institution
08007 BARCELONA
Spain
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.