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Gene editing and in vitro approaches to understand conceptus elongation in ungulates

Objective

In contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.

Fields of science (EuroSciVoc)

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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)

Programme(s)

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Topic(s)

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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.

ERC-STG - Starting Grant

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Call for proposal

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

(opens in new window) ERC-2017-STG

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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution

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.

€ 1 480 880,00
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
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.

€ 1 480 880,00

Beneficiaries (1)

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