Objective
Somatic expression of the retrogene DUX4 in skeletal muscle is associated with the development of the common myopathy facioscapulohumeral muscular dystrophy (FSHD). As FSHD patients mainly present with muscular symptoms, research in the FSHD field has focused on unraveling the functional consequences of DUX4 expression in skeletal muscle. Research on DUX4 expression in non-muscle tissues is limited, but increasing evidence suggests a biological function for DUX4 in somatic tissues. I aim to characterize DUX4 expression in non-muscle tissues, to determine the genome-wide transcriptional consequences of DUX4 expression, to identify DUX4 target genes in these tissues, and to establish whether treatment with DUX4 antisense oligonucleotides negatively impacts somatic tissues in which DUX4 has a biological function. First, I will use a combination of quantitative reverse transcriptase PCR, immunofluorescence staining, and flow cytometry to establish which tissues and what cell types express DUX4 in human and mouse. Next, I will use the innovative technique of single-cell RNA sequencing to determine the autonomous and non-autonomous functional consequences of DUX4 expression in DUX4-positive tissues. In parallel, to establish which genes and pathways are direct targets of DUX4 and whether tissue-specific differences exist, I will employ DUX4-chromatin immunoprecipitation sequencing. Finally, I will determine the effect of DUX4 suppression in vitro and in vivo. The proposed work will provide in depth analysis into the biological function of DUX4 in somatic tissues, contribute to the long-standing enigma in the field why FSHD presents as a muscle-specific disease, and provide guidance to DUX4-targeted therapies that are currently being developed.
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.
- medical and health sciences basic medicine neurology muscular dystrophies
- natural sciences biological sciences genetics RNA
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF-EF-RI - RI – Reintegration panel
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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.
(opens in new window) H2020-MSCA-IF-2017
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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.
2333 ZA Leiden
Netherlands
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.