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PReterm Enteroids to determine the Mechanism of Necrotising EnteroColitis

Objective

Necrotising enterocolitis (NEC) is an inflammatory mediated bowel disease that causes more deaths after the first week of life in extremely preterm infants than any other single pathology, with prematurity and abnormal bacterial colonisation regarded as the most significant risk factors. However, 40 years of research have yielded few advances in treatment and the mechanisms of disease remain poorly understood. A major reason for this lack of progress relates to challenges in translating findings from non-invasive samples (e.g. stool) and the inability to robustly model bacterial-host crosstalk. To overcome this longstanding hurdle, the proposed PREMNEC (PReterm Enteroids to determine the Mechanisms of Necrotising EnteroColitis) fellowship will utilise a novel ex vivo preterm human intestinal enteroid (PHIE) co-culture model to systematically explore the gut microbiome and host functioning in preterm infants.
The fellowship is divided in three distinct work packages (WPs). In WP1, surgically resected intestinal tissue (otherwise discarded) from NEC and non-NEC infants will undergo characterisation utilising metagenomics, transcriptomics, proteomics, and cellular imaging directly on the fresh tissue. Concurrently, WP 2 will isolate crypt cells from the tissue to establish PHIEs that permit accurate and reproducible ex vixo co-culture of bacterial-host interaction. In WP 3, bacterial species isolated from preterm infants will be systematically added to the ex vixo co-culture model and comparable technologies utilised in WP 1 will be applied to determine the pathobiology of disease. Newcastle University will provide expertise in state-of-the-art transcriptomics and cellular imaging technologies.
Upon completion of this 24-month fellowship, I will have pioneered significant advancement in the mechanistic understanding of microbial-host interaction in the pathogenesis of NEC and identified potentially beneficial bacteria that may provide protection from NEC.

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2017

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Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
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
KINGS GATE
NE1 7RU Newcastle Upon Tyne
United Kingdom

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Region
North East (England) Northumberland and Tyne and Wear Tyneside
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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