Project description
Novel genetic drivers of chronic kidney disease
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common malformations detected in utero and play a causative role in chronic kidney disease. Since molecular diagnosis is only possible in 20 % of the cases, elucidation of the underlying genetic causes of CAKUT is of major clinical relevance. Towards this goal, scientists of the EU-funded xenCAKUT project will generate a novel animal model for cystic kidney diseases in Xenopus tropicalis. Moreover, using genome editing methodologies, they will identify the genes central to pronephric tubule development in the embryo. Potential disease-causing genes will then be analysed, and through machine-learning based phenotyping it will be possible to model common genetic forms of kidney disease.
Objective
CRISPR/Cas9 has untapped potential for disease modeling in the diploid amphibian model organism Xenopus tropicalis (X. tropicalis). Here, I propose to employ state-of-the-art CRISPR/Cas9 technologies (in vivo CRISPR Screening, ShCAST, CRISPR-NSID) to address two current unmet clinical needs in congenital anomalies of the kidney and urinary tract (CAKUT). First, I will generate a novel animal model for autosomal dominant polycystic kidney disease (ADPKD) and investigate the role of a potential new druggable therapeutic target (ALDH1A1). Second, I propose to couple CRISPR screening methods to classical Xenopus animal cap differentiation assays to identify genes essential in the differentiation of pluripotent precursor cells towards pronephric structures. I intend to perform in vivo validation of hits to identify genes which underlie CAKUT development in X. tropicalis. Because a molecular diagnosis for CAKUT can currently only be made in about 20% of the clinical cases, the further elucidation of underlying genetic causes for CAKUT is of major clinical relevance. In vivo validated Xenopus CAKUT disease causing genes will be integrated with clinician networks (ERKNet, NEOCYST). This interdisciplinary approach will use well-established techniques from developmental biology, state-of-the-art CRISPR/Cas9 approaches, light-sheet-microscopy and machine-learning based phenotyping protocols to model common genetic forms of kidney disease using the diploid vertebrate model X. tropicalis.
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 developmental biology
- medical and health sciences clinical medicine nephrology kidney diseases
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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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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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2019
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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.
8006 Zurich
Switzerland
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.