Developing novel tools to probe the function of GPR37 within the CNS

An exciting drug discovery focused PhD studentship is available in the School of Life Sciences at the University of Sussex jointly supervised by Professors John Atack and Simon Ward. The aim of the project will be to identify novel modulators of GPR37 function and to use them as tools to explore the role of this receptor in neurodegenerative disease, and potentially provide starting points for a drug discovery project.
G-protein coupled receptors (GPCRs) mediate the transmission of extracellular signals into intracellular responses and they are therefore a major target for therapeutic drugs, including those within the central nervous system (CNS). GPR37 is a member of the Class A GPCR family and has been of particular interest since its initial description over 20 years ago based upon its almost exclusive expression within the CNS. This receptor modulates dopaminergic function and has been associated with a number of psychiatric disorder.
Despite these separate lines of evidence all indicating that GPR37 is a disease-relevant receptor, further examination of functional aspects of this receptor have, until recently, been hampered by its status as an orphan GPCR with an unknown endogenous ligand. However, GPR37 has very recently been “deorphanised” and its endogenous ligand recognised. Clearly, GPR37 is a potentially highly attractive therapeutic target although at the moment, and given the only very recent deorphanisation of this receptor, there is a lack of tools compounds with which to further explore the function of GPR37. Accordingly, the aim of this proposal is to identify compounds that selectively alter the function of GPR37 and examine the effects of such compounds in cellular and in vivo models relating to neurodegeneration, nerve injury and neuronal survival.
The project will provide excellent training in assay development and the student will benefit by being embedded with the Translational Drug Discovery group where there is a strong collaborative approach to scientific research. The group comprises individuals from industrial and academic backgrounds from organic, synthetic, medicinal and computational chemistries as well as molecular biology, neuroscience and computational biology. The group has a number of current multidisciplinary drug discovery projects, which would provide an exciting environment, coupled with active collaborations and links to major academic institute and industrial centres.
The placement at Janssen Pharmaceuticals in Beerse, Belgium will be a key component both to the student training and the progression of the project. Janssen scientists have the capacity and expertise to perform the mechanistic pharmacology that is essential to the project and they also have experience of working G-protein coupled receptors.