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Content archived on 2024-06-18

Mechanisms of earliest hematopoietic cell fate control

Objective

How blood cells and ultimately hematopoietic stem cells (HSCs) arise from uncommitted cells during development is only vaguely understood. Especially the initial formation of the first blood precursors in lateral mesoderm has been difficult to dissect. Investigating these early mechanisms of blood cell fate determination with genetic model systems provides a vital starting point for therapeutic drug discovery and the targeted manipulation of iPS cells to treat hematologic diseases. The goal of the proposed research project is to elucidate the mechanisms that drive uncommitted embryonic cells into a hematopoietic cell fate by using the vertebrate zebrafish (Danio rerio). To visualize, isolate, and fate-map the earliest stages of hematopoietic cell formation, the proposed work applies transgenic zebrafish reporters under control of the newly isolated draculin gene promoter/enhancer. draculin is the earliest marker for the emergence of hematopoietic cells from lateral mesoderm during embryo development. The transgenic labeling with draculin will be harnessed for progenitor culture assays to uncover the earliest hematopoietic cell fate potential of uncommitted lateral mesoderm. These experiments will be complemented with in vivo fate mapping using Tamoxifen-controlled Cre/lox methods. The proposed study will also apply novel zebrafish microinjection approaches to test and identify transcription factor combinations that enforce blood cell fates and HSC formation. The preliminary results revealed a combination of transcription factors that ectopically induces a hematopoietic gene program in the embryo. Altogether, this work will break new ground in our understanding of the earliest blood-forming mechanisms, and provide new insight into how cells can be experimentally guided towards the therapeutically desirable HSC fate.

Fields of science (EuroSciVoc)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2013-CIG
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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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

University of Zurich
EU contribution
€ 100 000,00
Address
RAMISTRASSE 71
8006 ZURICH
Switzerland

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Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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