AVS 51st International Symposium
    Biomaterial Interfaces Thursday Sessions
       Session BI-ThA

Invited Paper BI-ThA6
G-Protein Coupled Receptor Biosensors - New Opportunities and Applications

Thursday, November 18, 2004, 3:40 pm, Room 210D

Session: Biosensors and Bio-Diagnostics
Presenter: E.J. McMurchie, CSIRO Health Sciences and Nutrition, Australia
Authors: E.J. McMurchie, CSIRO Health Sciences and Nutrition, Australia
W.R. Leifert, CSIRO Health Sciences and Nutrition, Australia
L. Wieczorek, CSIRO Telecommunications and Industrial Physics, Australia
B. Raguse, CSIRO Telecommunications and Industrial Physics, Australia
Correspondent: Click to Email
Future diagnostic and biosensor platforms will require development of cell-free, high-throughput, microarray formats with bioengineered sensors mimicking the specific interactions between ligand and cell membrane receptors. For bio-diagnostic technologies, G-protein coupled receptors (GPCRs) are likely to have application as biosensors reporting on ligands influencing physiological and pathophysiological functions. GPCRs are a large and ubiquitous class of membrane-associated receptors activated by a wide range of extracellular ligands, (biogenic amines, amino acids, ions, peptides, and bioactive lipids) which act as hormones, neurotransmitters, chemokines etc. Signalling through these receptors regulates responses such as neurotransmission, chemotaxis, inflammation, cell proliferation, muscle contractility, and visual and chemosensory perception. GPCRs signal to numerous down stream cellular effectors via a set of heterotrimeric G-proteins through GTP dependant processes. GPCRs are the target for >50% of current therapeutic drugs with drug discovery programs relying on high throughput screening technologies. The future development of microarray technologies for GPCRs is relevant for the development of highly specific ligands in drug discovery and for utilising GPCRs as potential biosensors. Present assays for ligand screening against GPCRs can be classified into two major categories; whole cell assays with cell-associated, down-stream signalling systems for detecting activated receptors, and homogeneous, cell-free assays consisting of membrane fragments containing (usually cloned) GPCRs. For the latter, some form of signalling/reporting system must be added if functional assays, as opposed to ligand binding, are to be used. Our strategic objective is the construction of a cell-free system to enable reconstitution and nanoconstruction onto appropriate surfaces for future adaptation to microarray formats suitable for high throughput, multiplex screening.