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TNFaLysMyr SIGNED

Unique TNFα lysine myristoylation; elucidating its function, regulation and integration into inflammation

Total Cost €

0

EC-Contrib. €

0

Partnership

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 TNFaLysMyr project word cloud

Explore the words cloud of the TNFaLysMyr project. It provides you a very rough idea of what is the project "TNFaLysMyr" about.

cytokine    first    tnfa    secretion    signalling    cells    proteins    biology    kmyr    cell    lysine    secreted    cytokines    line    tools    residue    tag    chemical   

Project "TNFaLysMyr" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
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 Coordinator Country United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme /MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 183˙454.00

Mappa

 Project objective

Tumour Necrosis Factor-alpha (TNFa) is an important cytokine implicated in many autoimmune and inflammatory disorders, in which TNFa-blocking antibody drugs have become first line treatment. Nevertheless, clinical responses are variable. To improve and expand therapeutic strategies, a better understanding of TNFa and the many other cytokines secreted from cells is crucial. It was recently shown that TNFa is myristoylated on a lysine residue (KMyr), a unique modification that suggests an important but yet unexplored role for KMyr in cytokine biology. I will investigate the impact of KMyr on TNFa signalling, and its wider role in secretion and signalling of other cytokines, using a unique multi-disciplinary approach combining state-of-the-art chemical biology tools with molecular cell biology and proteomics. The role of KMyr in TNFa trafficking, secretion and signalling will be identified using human macrophage cell lines that produce mutant TNFa proteins with the relevant lysine residue substituted or deleted. KMyr proteins will be identified through a powerful approach that introduces a small chemical tag into the myristate in cells; this tag can be selectively functionalized to allow sensitive fluorescence imaging of KMyr within living cells, and purification for identification by mass spectrometry. The global scope of KMyr in the proteome will be analyzed in parallel, with emphasis on other secreted cytokines such as IL1alpha, which may be controlled too via KMyr. Regulation of TNF KMyr will be explored by identifying KMyr transferases and demyristoylases using chemical photo-affinity tools that can bind proteins interacting with KMyr, yielding putative targets for future first line therapies.

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lastchecktime (2019-11-15 7:38:32) correctly updated