Objective
For almost a century we have been able to control diabetes with insulin injections, yet we still have no cure for this prevalent disease. One possible way to cure diabetes is by increasing the number of insulin-producing β-cells in the pancreas. Here, I propose to uncover factors and mechanisms that can increase β-cell numbers through cellular reprogramming. To do so, we will use two complementary discovery approaches—and transition between zebrafish, mouse and human analyses—to perform functional studies with high translational value.
First, we will use a novel drug discovery approach in transgenic zebrafish to identify and characterize small molecules that can promote the reprogramming of various pancreatic cell types to β-cells. Second, we will use single-cell RNA-sequencing to identify genetic signatures of cellular reprogramming to β-cells in humans, and then dissect the function of the identified genes by overexpressing or mutating them in transgenic zebrafish. We will also use lineage-tracing to determine the number and origin of the β-cells the small molecules and genes induce.
Once we identify promising hits in zebrafish, we will treat diabetic mice with small molecules or secreted proteins (targeting the signalling pathways regulated by the hits) and evaluate their effects on glucose control and β-cell mass. We will also test their effects on cellular reprogramming in mice, as indicated by changes in the relative proportion of each hormonal cell type, in the generation of bihormonal cells (insulin+ glucagon+ or insulin+ somatostatin+), and in the number of lineage-traced β-cells. Further, we will determine whether these small molecules or secreted proteins induce reprogramming to β-cells in human islets.
By coupling whole-organism screens with mechanistic and translational studies, we will identify factors and pathways that can enhance cellular reprogramming to β-cells and could thus form the basis of a cure for diabetes.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-COG - Consolidator Grant
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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) ERC-2017-COG
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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.
751 05 Uppsala
Sweden
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.