Abstract: The invention generally relates to optical methods for the diagnosis of neuronal condition by converting a cell from a patient into a neuron and optically evaluating action potentials of that cell in vitro. The cell is transformed with an optical reporter and exhibits an optical signature in response to neural stimulation. Using genome-editing, a control cell can be made that is isogenic but-for a known mutation and a control signature obtained from the control cell. Thus, methods of the invention reveal potential neurodegenerative effects of a mutation as manifested in a patient's genetic context. The optical signature of the cell, or the difference between the signature and the control signature, is correlated to a diagnosis of the neurodegenerative disease.

Abstract: The invention provides an open-stage near-TIRF microscope in which all of the optical components are positioned underneath the sample, allowing for physical access to, and control over the environment of, the sample. The microscope can be used to image cells expressing fluorescent voltage indicators. Since the TIRF components do not interfere with the sample, living cells can be studied using a microscope of the invention. Where a sample includes electrically active cells expressing fluorescent voltage indicators, the microscope can be used to view voltage changes in, and thus the electrical activity of, those cells.

Abstract: The invention generally relates to optical methods for the diagnosis of neuronal condition by converting a cell from a patient into a neuron and optically evaluating action potentials of that cell in vitro. The cell is transformed with an optical reporter and exhibits an optical signature in response to neural stimulation. Using genome-editing, a control cell can be made that is isogenic but-for a known mutation and a control signature obtained from the control cell. Thus, methods of the invention reveal potential neurodegenerative effects of a mutation as manifested in a patient's genetic context. The optical signature of the cell, or the difference between the signature and the control signature, is correlated to a diagnosis of the neurodegenerative disease.

Abstract: Screening compounds by exposing a plurality of cardiomyocytes to a compound, wherein the cardiomyocytes express an optogenetic reporter of membrane potential and an optogenetic reporter of calcium level; receiving light from the optogenetic reporter of membrane potential; creating an AP waveform using the received light; and analyzing the AP waveform to determine the presence or absence of a risk for arrhythmia associated with the compound.

Abstract: The present invention provides, in part, platforms for analyzing an aspect of synaptic vesicle cycling. According to other aspects, the invention provides neuronal cell culture platform and platforms for analyzing an aspect of synaptic vesicle cycling. According to other aspects, the invention provides methods of measuring an aspect of synaptic vesicle cycling in a plurality of cells. According to other aspects, the invention provide methods for identifying a test agent as a modulator of an aspect of synaptic vesicle cycling.

Abstract: The invention generally relates to optical methods for the diagnosis of neuronal condition by converting a cell from a patient into a neuron and optically evaluating action potentials of that cell in vitro. The cell is transformed with an optical reporter and exhibits an optical signature in response to neural stimulation. Using genome-editing, a control cell can be made that is isogenic but-for a known mutation and a control signature obtained from the control cell. Thus, methods of the invention reveal potential neurodegenerative effects of a mutation as manifested in a patient's genetic context. The optical signature of the cell, or the difference between the signature and the control signature, is correlated to a diagnosis of the neurodegenerative disease.

Abstract: The invention generally relates to optical methods for characterizing the effects of compounds on pain and other sensory phenomena. The effect of compounds on pain and other sensory phenomena may be characterized using dorsal root ganglion (DRG) neurons or sensory neurons expressing optogenetic proteins that allow neural activity to be stimulated and detected optically. The invention provides cell-based optical assays for studying the molecular and cellular bases of pain and sensory phenomena and as platforms to screen and validate drugs, e.g., for pre-clinical trials.