Dr. Derek Bowie is the Director of the FRQS-funded research group, GEPROM, and has been a Professor at McGill University since 2002. He is the recipient of the Canada Research Chair award in Receptor Pharmacology and serves on the editorial boards of the Journal of Physiology, Current Neuropharmacology and Channels. Dr. Bowie earned his Ph.D. at the University of London after completing his undergraduate degree at Strathclyde University in Scotland. He then carried out postdoctoral training in France (Université Louis Pasteur), Switzerland (University of Zurich) and the USA (National Institutes of Health) before holding a faculty position at Emory University in Atlanta.
The Bowie Lab uses a combination of techniques to study ionotropic glutamate receptors (iGluRs), GABA-A receptors and more recently, Na+ channels. Excitatory iGluRs and inhibitory GABA-A receptors are neurotransmitter-gated ion-channels that dominate chemical signalling in the brain. Voltage-gated Na+ channels are responsible for the rapid upstroke of the action potential and electrical signalling in neuronal circuits. All ion-channel families are widespread in the vertebrate brain and fulfill many important roles in healthy individuals as well as being implicated in disease states associated with postnatal development (e.g. autism, schizophrenia), cerebral insult (e.g. stroke, epilepsy) and aging disorders (e.g. Alzheimer's disease, Parkinsonism). Each ion-channel family has been targeted for the development of therapeutically-relevant compounds. We are looking at iGluRs, GABA-A receptors and Na+ channels at two inter-related levels.
In molecular terms, we are examining the events that occur when each ion-channel family is activated with the aim of developing novel therapeutic compounds. All ion-channel families are studied primarily using patch-clamp electrophysiology to understand their functional properties. This work is complemented with fluorescence imaging and molecular biology approaches. We also collaborate with structural and computational biochemistry labs to understand how these ion-channels operate at atomic resolution. In recent years, the lab has focused on identifying how pore-forming and auxiliary subunits affect the functional behavior of the ion-channel signalling complex. Amongst other things, this work led to the discovery of ion-dependent gating of iGluRs that has motivated our understanding of why different iGluR subtypes have distinct functional properties and how they may have emerged during evolution.
At the cellular level, we are studying the role that iGluRs, GABA-A receptors and Na+ channels fulfill in shaping the behaviour of neuronal circuits and how these processes may be corrected in disease states. Recently we have focused on understanding how these ion-channels shape distinct neuronal circuits of the developing and adult cerebellum. The cerebellum is a brain region traditionally associated with motor learning and coordination; however, emerging data suggest that defects within these circuits may lead to neurodevelopmental disorders such as autism. We study cerebellar circuits using patch-clamp electrophysiology techniques in combination with cellular imaging using multiphoton microscopy. This work is often complemented with neuroanatomical approaches. To study defects associated with autism, we compare the network properties of the cerebellum from wildtype and genetically-modified mice that lack the gene responsible for Fragile X syndrome; a neurodevelopmental disorder that represents the most common single-gene cause of autism and inherited intellectual disability. To date, this work has focused on understanding the coupling between neuronal communication and cellular metabolism. In particular, we have identified the role of reactive oxygen species as key regulators of a novel form of inhibitory GABAR synapse plasticity.
Derek Bowie, B.Sc., Ph.D.,
Professor (Full), Department of Pharmacology & Therapeutics, McGill University
Director, GEPROM-a FRQS-funded research group
Editor, Journal of Physiology (London)
Bellini Life Sciences Complex, Room 164, McGill University,
3649 Promenade Sir William Osler, Montreal, QC, Canada H3G 0B1
Email: derek.bowie [at] mcgill.ca
Tele: (514) 398-1581 (office); -3715 (lab); -2513 (staff)
Fax: (514) 398-6690
Lab webpage: http://www.medicine.mcgill.ca/pharma/dbowielab