Objective
Many important biological processes involve binding of proteins to carbohydrates, including the recruitment of immune cells to tissues by proteins called selectins. The core binding requirement of all three types of selectins is a four sugar unit called the Sialyl LewisX epitope. However, affinity for this epitope alone is low. Further requirements for binding of selectins to their glycoprotein ligands include other carbohydrate and protein moieties, as well as sulfation of the carbohydrate or tyrosines. Open questions include what is necessary and sufficient for tight binding to each selectin, what sorts of ligands can bind to all selectins, and how the binding requirements can be presented on a synthetic scaffold. Answers to these questions will lead to a better understanding of the selectins, tools for future biological studies, and hopefully new medications for the many immune disease processes in which their abnormal functioning has been implicated.
I will combine my background in peptide selection technologies with the host expertise in lectins and bio-orthogonal chemistry to bring the power of evolution-based techniques to bear on these questions. Carbohydrates and sulfotyrosines will be incorporated in a scaffold of genetically tagged macrocyclic peptides, then selection pressure will be applied to a hugely diverse library of random structures. This will provide ligands that can bind to each selectin, as well as ligands that can bind to all selectins, and subsequent comparison of these ligands will illuminate the particular requirements for interaction with each selectin, as well as revealing shared features recognized by all. In addition to an increased understanding of the selectins, through this project I will gain new expertise in the glycosciences, share my unique experience with in vitro peptide selections using genetic code reprogramming – a technique not currently used in any laboratory in Europe – and kick-start my independent research career.
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 pharmacology and pharmacy pharmaceutical drugs
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences clinical medicine oncology
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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.
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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-EF-ST - Standard EF
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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-2016
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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.
3584 CS Utrecht
Netherlands
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.