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SUGARSmart: Smart design of recombinant antibody fragments specific for carbohydrate molecules

Objective

The development of new approaches to explore the diverse role of glycans in normal and physio- pathological conditions of the cell is a major challenge. Our previous research recognized roles of anti-glycan recognition molecules (lectins and antibodies) in the diagnosis of diseases like cancer, immunity, and hyperacute rejection upon bioprosthetic transplantation etc. However, because of the structural complexity, well-established approaches for developing glycan-based therapeutics are limited.

To address this issues, SUGARSmart aims to develop a workflow for rational design of single-chain fragment variable (scFv) antibodies to enhance glycan recognition capabilities, both specificity- and affinity-wise (improving detection limits of assays). Three major aims will be pursued: First, we will apply molecular modeling to predict mutations which lead to enhance affinity and specificity of anti-αGal scFv. A range of mutational strategies will be tested in order to learn which scFv domains, which particular locations (functionally important sites), and which mutations (aromatic or polar) are best suited to improve affinity and specificity. Second, computationally predicted mutants will be obtained by mutagenesis or chain shuffling. Validity of the predictions will be tested by affinity-measurement (ITC/SPR), array techniques and ELISA. At the end, validation of computational models of scFv-glycan interactions with experimental techniques will enable us to propose a workflow to engineer other anti-glycan scFv antibodies.

Overall, this project proposes an interdisciplinary approach to enhance our ability to quantify and engineer glycan recognition molecules having potential application in the smart and tailored development of future diagnostic reagents and therapeutics. To the best of our knowledge this will be the first attempt to provide a complete and coherent framework for anti-glycan antibody engineering, combining a wide computational pipeline and experiments.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

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.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

UNIVERSITY OF GALWAY
Net EU contribution

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.

€ 175 866,00
Address
UNIVERSITY ROAD
H91 Galway
Ireland

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Region
Ireland Northern and Western West
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 175 866,00
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