Objective
NK cells are relevant to many kinds of disease, including viral infection, autoimmunity, cancer, transplantation and reproduction. The behavior of NK cells is controlled by a large number of different cell surface receptors, in a region on chromosome 19 called the LRC. Some of these receptors, such as KIR, are highly variable in gene number and allele sequence in different individuals. Many of them interact with HLA class I molecules, which are also highly polymorphic. To understand and exploit NK receptors and disease this project has three aims:
1. To investigate how variation in receptors encoded in the LRC influences viral infection and disease course.
My laboratory is known for high-throughput KIR copy number and allele typing. Highly polymorphic KIR receptors are refractory to analysis by SNP typing and next generation sequencing (NGS) methods, so interrogation of large numbers of samples for accurate disease determination is not feasible. To overcome this problem we propose to develop digital PCR, sequence-based allele typing, imputation and NGS after sequence capture. Once underway, a large number of disease cohorts and matched controls will be investigated, spanning autoimmunity, infection and birth-weight, in collaboration with other laboratories.
2. To investigate mechanisms viruses use to evade NK cells.
To facilitate this we have generated reporter cells that permit weak interaction of receptors with their ligands to be detected by production of Green Fluorescent Protein (GFP). The evasion of NK cells by HCMV, vaccinia and HPV viruses will be studied. This work will be in conjunction with expert virology groups in the UK.
3. To identify novel ligands for LRC-encoded receptors.
We will use the reporter cells to screen for ligands, initially by blocking binding with monoclonal antibodies. We intend to identify ligands for KIR and LILR, where these are unknown, especially focusing on activating receptors.
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 microbiology virology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine transplantation
- medical and health sciences health sciences infectious diseases DNA viruses
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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)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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-ADG - Advanced 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-2015-AdG
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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.
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.