|Crystal structure of a human GABAA receptor (Miller & Aricescu, 2014).|
|Conformational plasticity of type IIa receptor protein tyrosine phosphatases facilitates proteoglycan binding (Coles at al, 2011).|
A. Radu Aricescu
Professor of Molecular Neuroscience
We are interested in understanding the molecular mechanisms responsible for acquisition and storage of information in the brain, i.e. learning and memory. Research over the past five decades led to the idea that activity-dependent changes in the strength of synapses between neurons may represent a mechanism for information storage. The neurotransmitters glutamate and gamma-amino-butyric acid (GABA) mediate most synaptic signalling in the vertebrate central nervous system. Physiologically, at synaptic sites, their receptors are incorporated into complex protein networks that span the inter-neuronal cleft and are essential for the in the induction, expression and/or modulation of synaptic plasticity. On the other hand, dysfunction of the same molecular systems appears to be responsible for the cognitive decline linked to the 'normal' aging process as well as a wide spectrum of neurological and psychiatric disorders including Alzheimer's, schizophrenia, Parkinson's, epilepsy, insomnia and major clinical depression.
Research in our group is currently focused on the structural and functional characterisation of synaptic receptors, our main tools being X-ray crystallography (to gain high resolution information) and increasingly electron microscopy (to study non-periodical, supra-molecular assemblies). We aim to understand principles governing the molecular organisation of neuronal synapses, and to devise ways of modulating synaptic function.
Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins
Elegheert J. et al, (2018), Nature Protocols, 13, 2991 - 3017
Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships
Zhang P. et al, (2018), Cell, 174, 1450 - 1464.e23
Glutamate receptor δ2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome
Berridge G. et al, (2018), Neurology, 91, e714 - e723
nandb—number and brightness in R with a novel automatic detrending algorithm
Nolan R. et al, (2017), Bioinformatics, 33, 3508 - 3510
Structural basis for GABAA receptor potentiation by neurosteroids
Miller PS. et al, (2017), Nature Structural & Molecular Biology, 24, 986 - 992