Development of Glutamate Biosensors using the Ionotropic Glutamate Receptor GluR2

PhD defense by Nathalie Rieben.

Abstract
Glutamate is the most abundant fast excitatory neurotransmitter in the mammalian nervous system and acts through a variety of ionotropic and metabotropic receptors. It has been shown to be involved in epilepsy, ischemic stroke, schizophrenia, Alzheimer's disease and Huntington's chorea among others. Development of sensors combining high sensitivity and low material consumption is of major importance for different applications in vitro and in vivo, such as diagnosis and drug discovery. The ionotropic glutamate receptor AMPA subunit GluR2 makes an excellent candidate for engineering such biosensors, due to its high affinity towards glutamate (nanomolar range) and because its ligand-binding domain has been engineered to permit its expression as an isolated, soluble protein (GluR2-S1S2) that exhibits similar pharmacology to the full length receptor.

This thesis describes the development of two sensors exploiting the conformational changes of GluR2-S1S2. Functional GluR2-S1S2 was interfaced with solid surfaces, with the aim of creating (I) an optical GluR2-based biosensor, and (II) a label-free GluR2-based biosensor using nanowire field effect transistors
(NW-FETs).

Supervisor: Karen Martinez