Lead Research Organisation: University of Surrey
Department Name: Veterinary Medicine & Science


Many G-protein coupled receptors (GPCRs) previously suspected to exist as membrane receptor monomers are expressed on the plasma membrane as homo/heterodimers or multimers. This concept is becoming widely accepted and constitutes an emerging area in the field of GPCR cell signalling. This study seeks to characterize a model GPCR heteromer at the cellular, biochemical and pharmacological level. We have previously identified that two key neuromodulatory receptors, the Histamine 3 receptors (H3) and Dopamine D1 receptors (D1), can complex into heteromers. Reappraisal of H3 pharmacology with focus on heteromers and in light of our more current appreciation of the complexity of GPCR ligands and downstream signalling (bias and allosterism) may lead to breakthroughs in understanding of neural control. A challenge in studying H3 is the presence of multiple isoforms (splice variants) of the receptors. These isoforms vary predominantly in the size of the third intracellular loop of the receptor. In some cases it appears that these isoforms can co-exist in the same cell. An aspect of the study will be to investigate pharmacological differences between isoforms, and understand how this contributes to physiological function of H3. Ligands selective for H3 heteromers over homomers will serve as powerful tools to probe heteromer function, and a further aspect of the study will be to identify such selective compounds either amongst known H3 ligands or through screening approaches. The final aspect of the study, and a critical question facing the field of research into GPCR heteromers, is to understand how heteromer formation is regulated. Simply the presence of different GPCRs with mutual affinity in the same cell membrane may be sufficient to drive transient or long-lasting association, but there is preliminary evidence of temporal regulation of heteromer formation. To begin to understand this, the project will investigate structural features important to heteromer formation.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/N504282/1 30/09/2015 29/09/2016
1649352 Studentship BB/N504282/1 30/09/2015 29/09/2019 Juliane Nathalie Appelhans
BB/N504282/2 30/09/2016 30/03/2018
1649352 Studentship BB/N504282/2 30/09/2015 29/09/2019 Juliane Nathalie Appelhans