ProfessorMacdonald Christie

Professor Christie's research has heralded numerous 'firsts'. He contributed to the first cloning of the D2 dopamine receptor (Nature) and achieved the first expression of a mammalian voltage-gated potassium channel (Science), and first functional demonstration of its heteropolymerisation (Neuron). His later research uncovered the mechanisms of plasticity of G-protein receptor coupling in neurons that are transforming thinking regarding opioid tolerance and ion channel plasticity in chronic pain states. His group discovered that µ and ? opioid receptors in nerve cells share common G-Protein receptor coupling mechanisms and provided the first evidence of direct coupling of µ-receptors to GIRK channels and of coupling of the opioid-related receptor ORL1, to GIRK channels in brain as well as in cannabinoid signaling. He discovered a novel signalling mechanism for G-Protein Coupled Receptors (GPCR) in synapses in brain (Nature). This provided a basis for seminal findings on plasticity of signaling in opioid withdrawal published in Neuron (2005) and Nature Neuroscience (2011).

Currently, Professor Christie continues to study opioid receptor regulation in pain and analgesia, in particular the processes driving the development of opioid tolerance. His team is investigating the molecular mechanisms responsible for tolerance at the µ-opioid receptor, action-related learning and plasticity in the cortico-striatal network, and studying novel GPCR mechanisms to treat neural hyper-excitation in chronic pain. These studies on intracellular signal bias aim to develop novel therapeutics for pain and addiction that could potentially preferentially divert signaling toward pathways associated with increased analgesic efficacy and lower rates of tolerance and/or fewer adverse effects.