Explore the words cloud of the iRhomADAM project. It provides you a very rough idea of what is the project "iRhomADAM" about.
The following table provides information about the project.
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
|Coordinator Country||United Kingdom [UK]|
|Total cost||212˙933 €|
|EC max contribution||212˙933 € (100%)|
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
|Duration (year-month-day)||from 2020-09-01 to 2022-08-31|
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|1||THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD||UK (OXFORD)||coordinator||212˙933.00|
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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