Project description
Structural insight into dendritic cell antigen recognition
Dendritic cells (DCs) express on their surface the receptor DC-SIGN, which binds and discriminates self and pathogen polysaccharide (glycan) patterns, thereby driving immune responses. The scope of the EU-funded Glycan-PMN project is to shed light on the structural determinants of this binding as well as the underlying immune regulation mechanism. Scientists will use nanoparticles functionalised with different glycans on their surface to determine the optimal structure for DC-SIGN binding. With the help of in vitro infection models, they will also evaluate the potential of targeting DC-SIGN with specific glycans to block infection or develop effective immunotherapies.
Objective
Multivalent lectin-glycan interactions is central to pathogen infection and immune response regulation. Dendritic cell (DC) surface tetrameric lectin, DC-SIGN, is particularly important in discriminating self- and foreign (pathogen) glycan patterns and regulates DC immune response. The underlying structural and immune regulation mechanisms remain poorly understood. As various lectins have overlapping glycan specificity, this greatly limits our ability to design glycoconjugates that can specifically target DC-SIGN to block infection or exploit its powerful immune regulation to develop effective immunotherapies.
Here we will address this challenge by developing polyvalent glycan-gold nanoparticles (GNPs) & multiple GNP assemblies to enhance binding affinity and specificity by exploiting multivalency. By tuning GNP surface glycan structure, valency, inter-glycan spacing, size and shape and study their binding with DC-SIGN/R, we will reveal the optimal glycan structure for DC-SIGN binding. By exploiting GNP’s fluorescence quenching, we will develop a new lectin-glycan affinity quantifying method. We will use glycan-GNPs to block pseudo-Ebola virus infection of DC-SIGN expressing cells and correlate the affinity and inhibition potency. We will study how glycan-GNP binding controls DC surface DC-SIGN clustering, binding to intracellular proteins & regulating cytokine production to reveal the .
This research is extremely timely & important because it will, 1) establish a design rule for potent, highly specific DC-SIGN targeting; 2) develop a new lectin-glycan affinity quantification method; 3) reveal correlation between DC-SIGN/R binding affinity & viral inhibition potency; 4) elucidate how DC-SIGN-glycan binding signal is transduced to regulate DC immune function, paving way to develop effective immunotherapies against deadly immune-dysregulation diseases (e.g. cancer, allergy, & auto-immune diseases) by exploiting DC-SIGN’s powerful immune regulation function.
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 basic medicine immunology autoimmune diseases
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine allergology
- medical and health sciences basic medicine immunology immunotherapy
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
LS2 9JT Leeds
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.