The STING (stimulator of interferon genes) signalling cascade is a recently discovered pathway with a unique role in innate immunity. STING signalling controls interferon-β (IFN-β) secretion, and aberrant activation of this pathway has been linked directly to serious disorders, including cancer, autoimmune disorders, and inflammatory conditions. Although the STING pathway has attracted considerable attention as a novel therapeutic target, the molecular mechanisms of this pathway are far from fully understood.
The central component of the STING pathway is the adaptor protein STING. The main endogenous ligand of STING is the non-canonical cyclic dinucleotide cGAMP (cyclic GMP-AMP), but the bacterial second messengers cyclic di-GMP and cyclic di-AMP are also recognised as ligands. Upon ligand binding, STING is activated via a complex mechanism, details of which appear to be ligand- and species-dependent. Clinically relevant single point mutations that affect STING activation have also been described.
The goal of this interdisciplinary project is the development of novel analogues and mimics of cGAMP to elucidate the mechanistic details of STING activation including the impact of clinically relevant mutations and to study STING signalling in cells. Results from this project will provide important new insights into this unique signalling pathway, and advance the development of novel therapeutics for cancer and inflammatory diseases.
The project is ideally suited for applicants with an interest and experience in medicinal/organic chemistry, who want to expand their skills in organic synthesis, and learn new experimental techniques e.g., in cell biology. Applicants should have a 1st or 2.1 honours degree (or equivalent) in Chemistry, Chemical Biology, Pharmacy, Pharmaceutical Sciences, or a closely related discipline. A strong interest in nucleotide chemistry is an advantage.
The position is available immediately and should be taken up no later than January 2022.
Applications will be reviewed on a rolling basis and the position may close early once a suitable candidate has been identified
Applications must be submitted electronically via the Queen’s Direct Applications Portal, including ALL required supporting documents, by the closing date.
Informal enquiries should be directed to [Email Address Removed]
The title of the studentship should be referenced in all correspondence