Following undergraduate studies at the University of Cambridge (BA St John's College, 1994), Nick Holliday obtained his PhD from King's College London (1998), supported by an AJ Clark PhD studentship from the British Pharmacological Society. During subsequent postdoctoral work in London, his interests in peptide messengers regulating appetite and metabolism became focused on molecular mechanisms underlying the signalling and regulation of their receptors. Nick was awarded a independent RCUK fellowship at the University of Nottingham in 2006, followed by Lecturer (2011) and Associate Professor (2013) positions. While at Nottingham, Nick's group has been funded by the MRC, charity, the Brazilian CAPES drug discovery program and industrial collaborations, and in 2011 he was awarded the Bill Bowman travelling lectureship from the British Pharmacological Society. He has also been actively involved in public engagement, including an arts crossover project to explain the use of imaging in pharmacology ("Hijacking Natural Systems"), funded by the Wellcome Trust.
GPCRs for peptides such as neuropeptide Y, gastrin releasing peptide and ghrelin, and nutrients such as free fatty acids, are implicated in the control of appetite, body weight and insulin secretion. They provide new drug targets to treat diabetes and obesity, and as such an understanding of the cellular mechanisms that regulate receptor function is crucial when considering long-term treatment of these conditions
Our group focuses on understanding the mechanisms underlying the signalling and intracellular trafficking of these GPCRs, and developing methods to assess ligand pharmacology for these processes. We have particular expertise in high content imaging and fluorescence / luminescence complementation approaches to develop GPCR protein-protein interaction assays, with the aim to study pharmacology at the level of individual signalling complexes and so better understand the effects of GPCR dimers and ligands which are signalling biased. Recently (in collaboration with Tom Bellamy), we are developing light (optogenetic) and "designer drug" activated receptors to explore spatiotemporal signalling in both model cell systems and astrocytes.
CAPES Drug Discovery program: Dr Liciane Medeiros, Stefania Ciaoto
PhD students: Rachel Richardson, Laura Humphrys, Jess Carpenter, Saori Mukaida, Aaron Horsey, Matt Gibbs
Signalling bias in peptide and dopamine receptors
Mechanisms of GPCR internalisation and intracellular trafficking defined through high content imaging
Allosteric interactions in peptide receptor homo and heterodimers
Optogenetic and chemogenetic stimulation of GPCR signalling
GPCR pharmacology (binding and signalling assays)
High content confocal imaging and analysis
Fluorescence and luminescence complementation to detect protein interactions
Optogenetic and designer G protein coupled receptors
B31ESP - Essential Skills for Phamacists (Year 1, MPharm 40 credit)
C12PBT - Pharmacological Basis of Therapeutics (year 2, BSc, 20 credit)
A13GPD - GPCR polymorphisms, disease and personalised medicine (Year 3, BMedSci)
B33PPM - GPCR based personalised medicine (Year 3, MPharm)
B34FME - Future Medicines (MPharm year 4)
Senior Tutor for the MPharm degree
SYKES DA, MOORE H, STOTT LA, HOLLIDAY ND, JAVITCH JA, LANE JR and CHARLTON SJ, 2017. Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors Nature Communications.
WONG, KELVIN, BRIDDON, STEPHEN J., HOLLIDAY, NICHOLAS D. and KERR, IAN D., 2016. Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 1863(1), 19-29