Project: Towards the structural and molecular basis of pro-inflammatory signalling assemblies mediated by IL-23 and IL-12
2018-01-01 – 2021-12-31
- Abstract
Mammalian cellular development and regulation of the immune system crucially depend on appropriate signalling pathways initiated by dedicated cytokine-receptor assemblies at the cellsurface. The downside of such a key physiological activity is that native and mutant forms of cytokines and their receptors are often pivotal to the initiation and progression of inflammatory disorders, cellular malignancies and cancer. Interleukin-12 (IL-12) and Interleukin-23 (IL-23) are the prototypic members of the IL-12 family of cytokines and have emerged as key therapeutic targets as a result of their role in pro-inflammatory responses in psoriasis, arthritis, airway inflammation, atherosclerosis, and cancer. Such functional plurality is additionally fuelled by the sharing of common features by IL-12 and IL-23 in terms of molecular organization and utilization of receptor modules.
The objective of the proposed research program in molecular structural biology is to provide long awaited insights into the structural and molecular basis of signalling assemblies mediated by IL-12 and IL-23 and the principles of receptor sharing among cytokines of the IL-12 family. Our research initiative builds upon recent experimental work and molecular tools generated in our group. We envisage that our work will greatly impact mechanistic and therapeutic interrogation of IL-12 and IL-23 mediated signalling.
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Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23
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- Journal Article
- A1
- open access
Activation of goblet-cell stress sensor IRE1β is controlled by the mucin chaperone AGR2
(2024) EMBO JOURNAL. -
- Journal Article
- A1
- open access
Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice
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- Journal Article
- A1
- open access
Pore-forming proteins as drivers of membrane permeabilization in cell death pathways
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- Journal Article
- A1
- open access
Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27
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- Journal Article
- A1
- open access
Structural basis of cytokine-mediated activation of ALK family receptors
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- Journal Article
- A1
- open access
Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting