Novel Multifunctional Probes

DESCRIPTION (provided by applicant): Classical visual probes operate by binding to and illuminating a target molecule of interest. However, most probes are limited in response to a single event, binding to a single target, or reporting a single phenomenon. This is a significant limitation for imaging of cellular events, which are characterized by complex signaling pathways composed of multiple, spatially-localized signals. Current reporters have a second limitation for detection cellular function - they rarely permit intracellular localization for more accurate discrimination of signaling events. Probes that can be localized (e.g. antibodies) often cannot be amplified for the visualization of infrequent events. Probes that can be spatially localized at the nanometer scale and can link multiple reporters simultaneously could have a major impact on biomedical research and diagnostics. The difficulty in constructing better reporting systems is not simply the development of new reporters, but the ability to control existing reporters using suitable vehicles. Traditional vehicles (liposomes and beads) have been successful for some applications, but have difficulty incorporating enzymes and membrane proteins, are difficult to localize, and are often unstable. The purpose of this proposal is to create a new class of molecular probe that can detect targets with high sensitivity, nanometer-scale spatial resolution, and multiple detection modalities.