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Decoding ISGylation events in Macrophages

Objective

The protein interferon stimulated gene 15 (ISG15) is a highly conserved ubiquitin-like modifier important for innate immune responses in mammals. ISG15 is highly abundant in cell lysates and enriched on the phagosome of interferon-activated macrophages. In humans, lack of ISG15 leads to increased susceptibility to infection by mycobacterial pathogens that reside in the phagosome of macrophages. However, both ISGylation events and their role are poorly characterized. This is partly due to the lack of analytical tools for the identification of ISGylation sites in cells. Here, I propose to develop a proteomics strategy to enrich and identify ISG15 targets that will also allow characterizing the interplay of ISG15 with ubiquitin. I will apply this method to analyze how ISGylation changes in response to Salmonella infection in macrophages. In order to understand the mechanisms that lead to susceptibility to intracellular pathogens, I will further use these approaches to test how ISGylation affects phagosome biogenesis in macrophages. ISG15 substrates identified in my proteomics screens will be validated and further characterized using biochemical, cell biological and immunological tools. Altogether, this data will provide new functional insights how ISG15 regulates defense mechanisms against bacterial infections.

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Keywords

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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 - 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.

(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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