Objective
The integrity of the genome transmitted to the next generation intrinsically relies on germline cells. Processes ensuring germ cell development, genomic stability and reproductive lifespan are essential for the long-term success of a species. Spermatogonial stem cells (SSCs) support spermatogenesis throughout life, the identity of this mammalian adult stem cell population in vivo remains unknown. Here, we propose analyze the contribution of both short and long non-coding RNAs to mammalian male germ cell development and SSC homeostasis. In the mouse male germline the small non-coding piRNAs and their interacting-Piwi proteins Mili and Miwi2 are essential for the establishment of epigenetic transposon silencing. Miwi2 is also required for the long-term survival of SSCs in adult mice and in contrast to Mili, Miwi2 is not broadly expressed during adult spermatogeneis. We found that Miwi2 is expressed in in vitro cultured SSCs and in a tiny population of adult testis cells in vivo. We will determine if Miwi2 expression identifies the illusive SSC population with long-term self-renewal capacity in vivo and explore the biology of this adult stem cell population as well as the molecular mechanisms by which the Miwi2-piRNA pathway governs SSC maintenance. We will also define function(s) beyond transposon silencing for Mili during spermatogenesis. Recently, transcriptome sequencing has reveled abundant and diverse classes of genes encoding long non-coding RNAs (lncRNAs) whose functions remains mostly unknown. We will explore the contribution this novel class of cellular RNAs in SSC self-renewal and differentiation. For the above, we propose using state-of-the-art mouse genetic strategies, high throughput sequencing, shRNA screening and proteomic approaches. In summary, this proposal aims to address basic questions at the intersection of non-coding RNA function and germ cell development/maintenance to reveal processes that underpin the integrity of the immortal lineage.
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 medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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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.
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.
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.
ERC-2012-StG_20111109
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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.
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.
Host institution
EH8 9YL Edinburgh
United Kingdom
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.