Recent improvements in target discovery and high-throughput screening
have increased the pressure at key points along the drug-discovery pip
eline. High-content screening was developed to ease the bottlenecks fo
rmed at the target-validation and lead-optimization points, and a new
generation of reagents that report on specific molecular processes in
living cells (fluorescent-protein biosensors) have been important in i
ts development. Creative designs of fluorescent-protein biosensors hav
e emerged and been used to measure the molecular dynamics of macromole
cules, metabolites and ions. Recent applications of fluorescent-protei
n biosensors to biological problems have provided a foundation for the
ir use in biotechnology.