Abstract: Disclosed are compositions and methods for their use, such as in identifying G-protein-coupled receptors, ligands and compounds that modulate the activities of G-protein-coupled receptors. The compositions and methods employ cyclic nucleotide-gated channels and fluorescence dyes in detecting changes of intracellular cAMP levels in response to the stimulation of G-protein-coupled receptors. Activation of the G-protein-coupled receptors can be detected in a variety of assays, including cell-based imaging assays with fluorescence microscopes and high throughput assays with multi-well plates and fluorescence plate readers.

Abstract: Disclosed are novel compositions and methods employing cyclic nucleotide-gated channels and fluorescence dyes and other indicators in detecting changes of intracellular cAMP levels, for instance in response to the stimulation of G-protein-coupled receptors. CNG mutants comprising one or more pore mutations that enhance sensitivity to cAMP and decrease divalent cation-mediated blockage are used in a variety of assays, including detection of the G-protein-coupled receptor activity. Also disclosed are novel dye quencher formulations that are particularly suited for cell-based assays of protein interactions.

Abstract: Disclosed are compositions and methods for their use, such as in identifying G-protein-coupled receptors, ligands and compounds that modulate the activities of G-protein-coupled receptors. The compositions and methods employ cyclic nucleotide-gated channels and fluorescence dyes in detecting changes of intracellular cAMP levels in response to the stimulation of G-protein-coupled receptors. Activation of the G-protein-coupled receptors can be detected in a variety of assays, including cell-based imaging assays with fluorescence microscopes and high throughput assays with multi-well plates and fluorescence plate readers.

Abstract: Disclosed are compositions and methods for their use, such as in identifying G-protein-coupled receptors, ligands and compounds that modulate the activities of G-protein-coupled receptors. The compositions and methods employ cyclic nucleotide-gated channels and fluorescence dyes in detecting changes of intracellular cAMP levels in response to the stimulation of G-protein-coupled receptors. Activation of the G-protein-coupled receptors can be detected in a variety of assays, including cell-based imaging assays with fluorescence microscopes and high throughput assays with multi-well plates and fluorescence plate readers.

Abstract: A microscope optical system in which both a sample and the viewing optics can be maintained stationary, while at the same time different points or fields of view of the sample can be examined. In the microscope optical system a sample is provided, e.g. on a stage, to be maintained in a stationary position when the sample is viewed. Further, viewing optics of the microscope optical system can be maintained in a stationary position when the sample is viewed. Intermediate optics between the stage and the viewing optics are moveable so that different portions of the sample can be examined without having to move the sample and without having to move the viewing optics.

Abstract: The present invention relates to methods of identifying drug-resistant and/or drug-sensitive cells, for example, breast cancer and brain tumor cells, on the basis of different ion and/or second messenger dynamics between a drug-sensitive and drug-resistant cell. For example, the invention provides measuring the comparative decay rates of a cellular ion, such as calcium, released into the intracellular compartment of drug sensitive and/or drug resistant cells. The present invention also provides methods for screening compounds that modulate the ionic dynamics of a cell as well as methods of determining drug resistance/sensitivity of cancer cells from cancer patients and/or designing cancer therapy based on of the ionic dynamics of cancer cells from a particular patient.

Abstract: A microscope optical system structure in which both a sample and the viewing optics can be maintained stationary, while at the same time different points or fields of view of the sample can be examined. In the microscope optical system structure a sample is provided, e.g. on a stage, to be maintained in a stationary position when the sample is viewed. Further, viewing optics of the microscope optical system can be maintained in a stationary position when the sample is viewed. Intermediate optics between the stage and the viewing optics are movable so that different portions of the sample can be examined without having to move the sample and without having to move the viewing optics.