Project description
Insight into neuronal development offers cues for cell therapy
Parkinson’s disease (PD) is a progressive disorder of the central nervous system that affects mainly the dopaminergic neurons. Understanding the developmental pathways of these cells will provide a better insight into PD and cell-based therapies. The GRAIN project is funded by the Marie Skłodowska Curie Actions programme and aims to investigate the differentiation mechanisms of mesencephalic dopaminergic neurons. Researchers will focus on the gene regulatory networks implicated in this pathway as well as on Notch signalling. GRAIN results will help improve stem cell differentiation protocols and cell therapy approaches for PD.
Objective
Stem cell-based therapy is an attractive way to treat a panel of as-yet incurable diseases, amongst which is Parkinsons Disease, caused by the progressive degeneration of mesencephalic dopaminergic (mesDA) neurons. To make this a reality, efficient and precise differentiation protocols of human embryonic stem cells (hESCs) need to be developed. While a protocol for differentiation of mesDA neurons exists, little is known about the resulting progenitors homogeneity and the mechanisms that control their maintenance, expansion and differentiation. MesDA neurons arise from ventral midbrain progenitors, whose differentiation requires the transcription factor Neurogenin 2 (NGN2). NGN2 acts as a master regulator by binding to, and stimulating transcription of, a panel of poorly defined target genes, while itself negatively regulated by HES1, one of the main effectors of Notch signalling. Yet, the involvement of Notch signalling in mesDA differentiation and the composition of the HES1/NGN2 gene regulatory network (GRN), i.e. the group of genes under their transcriptional control, in this context remains largely unknown.
The aim of this action is to determine the mechanisms by which HES1, NGN2 and their GRN control mesDA differentiation. Building upon and expanding existing tools and knowledge in the host lab, I will use a multidisciplinary approach combining genome editing and hESC biology to derive mesDA progenitors from a panel of wildtype and HES1/NGN2 KO hESCs cell lines, with a multiomics approach to define the members of the HES1/NGN2 GRN and unravel its mechanism of action. The synergy between the expertise of the host lab in developmental and stem cell biology, and my extensive knowledge of bioinformatics and experience in the generation of multiomics datasets, will allow to both improve the efficacy and quality of the current mesDA differentiation protocols, as well as expand fundamental knowledge about the architecture of GRNs regulated by Notch signalling.
Fields of science (EuroSciVoc)
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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.
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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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1165 KOBENHAVN
Denmark
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.