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iRhomADAM SIGNED
Uncovering the role of the iRhom2-ADAM17 interaction in inflammatory signalling
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0iRhomADAM project word cloud
Explore the words cloud of the iRhomADAM project. It provides you a very rough idea of what is the project "iRhomADAM" about.
inflammation
interface
mode
cleavage
hallmark
helical
human
irhom2
peptides
fret
autoimmune
inhibitor
aberrant
first
last
dissect
cytokine
cancer
effect
protein
mechanistic
emphasis
irhom
interaction
prevalence
model
competitively
primary
rising
diseases
overarching
inflammatory
signalling
designed
macrophage
syndromes
irhoms
metalloprotease
inhibit
adam17
tnfalpha
residues
stability
recognition
search
biology
trafficking
chronic
rationally
therapeutically
spectroscopy
maturation
shedding
vivo
transmembrane
regulate
significance
release
inhibitors
manipulate
assays
abolished
Project "iRhomADAM" data sheet
The following table provides information about the project.
| Coordinator |
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Organization address contact info |
| Coordinator Country | United Kingdom [UK] |
| Total cost | 212˙933 € |
| EC max contribution | 212˙933 € (100%) |
| Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
| Code Call | H2020-MSCA-IF-2018 |
| Funding Scheme | MSCA-IF-EF-ST |
| Starting year | 2020 |
| Duration (year-month-day) | from 2020-09-01 to 2022-08-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD | UK (OXFORD) | coordinator | 212˙933.00 |
Map
Project objective
The primary inflammatory cytokine, TNFalpha, is a transmembrane protein that requires cleavage by the metalloprotease ADAM17 for its release. Aberrant release of TNFalpha is a hallmark of cancer, chronic inflammation and autoimmune syndromes. The rising prevalence of these widespread diseases necessitates new approaches to manipulate inflammatory signalling, which is the overarching goal of this proposal. Recent studies demonstrate that iRhoms regulate trafficking, maturation and stability of ADAM17. Without iRhoms, TNFalpha shedding is abolished. The aim of this research is to dissect the transmembrane interaction between iRhom2 and ADAM17, which will support the required information to design the first iRhom inhibitor. Using FRET spectroscopy and ADAM17 activity assays, I will first search for essential residues at the transmembrane interface between iRhom2 and ADAM17. Next, I will use rationally designed helical peptides to competitively inhibit the transmembrane interaction. Last, I will test the effect of any inhibitors I develop in an in-vivo human macrophage model and use it to study the significance of this interaction. This study will provide an important mechanistic understanding of iRhom biology, with an emphasis on their mode of specific transmembrane recognition. Moreover, by developing the first specific iRhom2-ADAM17 complex inhibitor, I will establish iRhom2 and ADAM17 as therapeutically relevant targets to manipulate inflammation.
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The information about "IRHOMADAM" are provided by the European Opendata Portal: CORDIS opendata.
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