The proinflammatory cytokines IL17A, IL17F and IL17AF have been shown to signal via heterotrimeric signalling complexes formed with their receptors: IL17RA and IL17RC. Therapeutic antibodies targeting IL17A are currently available for the treatment of psoriasis and arthritis, while next generation therapies targeting both IL17A and IL17F are also being developed.
This project aims to fully characterize the structure and assembly of the IL17 signalling complexes, which is expected to inform the development of future therapeutics. The affinity of the IL17 dimers for the D1 and D2 domains of IL17RA and IL17RC will be determined in order to gain a thorough understanding of how the individual receptor domains contribute to the affinity of the interactions. An integrated structural biology approach involving NMR and crystallography will be used to solve the structures of the complexes, as well as explain the negative cooperativity observed during the assembly of the IL17/IL17RA/IL17RC signalling complex.
Academic entry requirements: UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.