Objective
In this proposal I wish to test the hypothesis that immune cells of the Natural Killer (NK) lineage use similar mechanisms to regulate both invasive placental cells and invasive cancer cells. Trophoblast cells and NK cells appear to come into close contact at the fetal-maternal interface during early pregnancy both in human and mice. Trophoblast cells indeed invade deep into the uterus while maternal NK cells accumulate adjacent to the invading trophoblast. These immune cells are a unique population and are known as uterine NK (uNK) cells. The interactions between trophoblast and uNK cells most likely influence the tissue remodelling that results in increased blood flow necessary for fetal growth. Thus, these interactions are key to successful reproduction but the molecular mechanisms are unknown and are the focus of this proposal. Like human uNK cells, also mouse uNK cells express activating receptors, such as the Natural Cytotoxicity Receptor NKp46, which is coded by the Ncr1 gene and is conserved in human, mice and many other species. NKp46 is a key receptor to recognise cancer cells. The host laboratory (lead by F Colucci) has shown that NKp46-deficient mice are more prone to metastatic melanoma (JCI, 2009) and that mouse trophoblast cells may express NKp46 ligands (unpublished). Considering the invasive properties of trophoblast, the question we wish to address is whether NKp46 controls the extent of trophoblast invasion, thereby affecting spiral arteries remodelling and fetal-placental growth. To address this question, we will compare trophoblast invasion, spiral artery modification and fetal-placental growth in NKp46-sufficient and NKp46-deficient transgenic mice.
The understanding of the molecular interactions between uNK cells and trophoblast will help define the role of uNK cells in reproduction and may have implications in cancer and transplantation.
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.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine obstetrics fetal medicine
- medical and health sciences clinical medicine transplantation
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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.
FP7-PEOPLE-2011-IEF
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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.
Coordinator
CB2 1TN CAMBRIDGE
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.