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Glycoprotein-based inhibitors of shiga-like toxin

Objective

Gastrointestinal infections have substantial impact in both the developing world and in Europe with 1.5 billion cases each year leading to approximately two million deaths each year, 760,000 of which are in children under five years old. Many of these deaths are caused by bacteria for example E. coli O157, that produces protein toxins, including shiga-like toxin (SLT). In the human body, the surfaces of living cells are covered in complex carbohydrate molecules. This “sugar coating” allows the cells to interact with viruses, bacteria, and toxins that have complementary protein receptors. The pentagonal shiga-like toxin produced by E. coli O157 bacteria can attach to five copies of a specific carbohydrate on the gut wall and enter cells lining the intestine. The result is bloody diarrhoea and the toxin entering the circulatory system to cause kidney failure.

In this project, we will make protein-based inhibitors that can prevent this toxin from attaching to, and enter kidney cells. The inhibitors will be synthetic glycoproteins that have 5 copies of the target sugar attached at specific sites so that they can bind to all 5 of the toxin’s receptor sites simultaneously providing an extremely strong interaction to prevent the toxin from entering cells. During the project we will synthesise a series of glycopeptides and attach them to pentameric protein scaffolds using site specific chemical and enzymatic modification. We will evaluate the glycoproteins as inhibitors of toxin adhesion and cell entry using a variety of cell and biophysical assays. The optimized inhibitors will have potential as a new class of future biopharmaceuticals.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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 LEEDS
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.

€ 183 454,80
Address
WOODHOUSE LANE
LS2 9JT Leeds
United Kingdom

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Region
Yorkshire and the Humber West Yorkshire Leeds
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.

€ 183 454,80
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