Rethinking receptor recognition in cytokines; their role in asthma and inflammation

The ‘four alpha-helix bundle’ cytokines (IL4/IL13 and IL6/IL11) have a broad range of functions and are crucial for fighting infection and the immune response. These cytokines are validated therapeutic targets as their dysregulation results in a broad spectrum of pathological conditions including inflammation (asthma, arthritis), sepsis and cancer.

Our previous studies of IL13 and IL6 (DOI: 10.3389/fimmu.2023.1216967) have indicated that they, and related cytokines, exist in at least two states – receptor competent and incompetent. This equilibrium state provides a new insight into the differing receptor signalling complex formation. We will use a combination of NMR spectroscopy, computational methods and functional assays to interrogate these conformations, enhancing our understanding of receptor recognition and protein-protein interactions in general. With this knowledge, the potential for the development of small molecule allosteric inhibitors that can trap the cytokine in an ‘incompetent’ state could be realised.

To apply please refer to our website https://le.ac.uk/study/research-degrees/funded-opportunities/liscb

Enquiries to Dr. Fred Muskett fwm1@le.ac.uk