Structure and protein motions of voltage and ligand gated channels. We have developed new methods for studying ion channel structure malignant histiocytoma and protein motion. We label channel proteins on the surface of living cells malignant histiocytoma in a site-directed manner with fluorescent dyes. We detect local protein motion via changes in the microenvironment malignant histiocytoma of the dye in real-time, with sub-millisecond resolution, by measuring fluorescence intensity, wavelength and dye mobility. These optical reports identify "what moves when" in relation to functional events that are synchronized for the malignant histiocytoma channel population and measured with a voltage clamp. In addition to obtaining kinetic maps of protein motion, we use fluorescence resonance energy transfer as a spectroscopic ruler malignant histiocytoma to make structural determinations. This method enables us to view movements of individual segments malignant histiocytoma of the channel protein, in individual subunits, so that the spatial location and role in gating of malignant histiocytoma each domain of the protein can be determined. From measurements of movement and distance we are working to malignant histiocytoma assemble an animated structural model of the conformational rearrangements that malignant histiocytoma activate, open, close and inactivate channels. In addition, we are now beginning to make optical measurements of protein malignant histiocytoma motion on the single channel level. Our work, which began with a voltage-gated K+ channel, is now expanding to other classes of channels that are malignant histiocytoma activated by very different classes of signals, such as ligand binding. Our aim is to discover general principles that enable different malignant histiocytoma kinds of signal transduction apparatus to control the conformation of malignant histiocytoma molecular gates that control ion flux and ion selectivity.
Development of genetically encoded optical sensors of cell signaling. Measuring electrical activity in large numbers of cells with high malignant histiocytoma spatial and temporal resolution is a fundamental problem for the malignant histiocytoma study of neural signaling. To address this problem, we have constructed a novel, genetically-encoded probe that can be used to measure transmembrane voltage malignant histiocytoma in single cells. We fused a modified green fluorescent protein (GFP) into the voltage-sensitive Shaker channel, creating a channel whose voltage-dependent rearrangements induce large changes in the fluorescence of GFP. A genetically manipulable voltage sensor has the advantage that its malignant histiocytoma operating range can be tuned by mutagenesis, and that it may be introduced into an organism and malignant histiocytoma targeted for expression to specific developmental stages, brain regions, cell types, and sub-cellular locations. We are using similar strategies to develop different optical sensors malignant histiocytoma by fusing this GFP to other detector proteins such as malignant histiocytoma channels and receptors. Such sensors can be used to ask specific biological questions malignant histiocytoma about the native role of the detector proteins, or, instead, to report on the signals that activate these proteins. We are using such sensors to determine the role of malignant histiocytoma signaling pathways in Drosophila synapse formation and in several other malignant histiocytoma model synaptic systems.
Using a new and relatively simple gene-therapy treatment, Berkeley scientists have restored enough sight in previously blind mice malignant histiocytoma that within a month they were navigating their environment with malignant histiocytoma the same ease as sighted mice. The treatment involved just one injection of a gene for malignant histiocytoma a green-light receptor into the eyes. "With neurodegenerative diseases of the retina, often all people try to do is halt or slow malignant histiocytoma further degeneration," says molecular and cell biology professor Ehud Isacoff, director of the Helen Wills Neuroscience Institute and one of malignant histiocytoma the study’s co-authors. "But something that restores an image in a few months malignant histiocytoma — it is an amazing thing to think about." The findings offer hope to roughly 170 million people around malignant histiocytoma the world with age-related macular degeneration, and 1.7 million people with a common form of inherited blindness, called retinitis pigmentosa. The team is now raising money to begin human trials malignant histiocytoma in the next three years. For more on this, see our press release at Berkeley News. Stories on this topic have appeared in dozens of sources, including the San Francisco Chronicle Online and Interesting Engineering.
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