Christopher Moore, Ute Hochgeschwender, Diane Lipscombe, Barry Connors, Julie Kauer
Real-time detection of subcellular events coupled to feedback control could prove revolutionary. Current solutions detect only extracellular signals, and require implanted hardware and computer-based detection algorithms. Brown University investigators are solving this problem with an all-molecular approach that allows cells to sense and correct their own activity patterns. They would engineer cells to express bioluminescent proteins that produce light only when local calcium levels increase. Light-sensitive proteins such as optogenetic effectors detect this light and, in turn, generate context-dependent outcomes, including suppression or excitation of the host cell. The team will focus this development on calcium, as brief calcium increases are essential for driving contraction in muscles, information processing in neurons and insulin release in pancreatic cells. These new tools will have broad research and clinical applications, including sensing and discontinuing aberrant activity before it can cause harm. This approach can potentially be adapted to re-wire communication between cells, as light generated in one cell can be detected by sensors in a partner. The investigators will test these methods in neurons, smooth muscle and pancreatic beta cells. This molecular feedback system can be applied to any signal that bioluminescent enzymes can detect (e.g., ATP, cAMP, pH), further expanding the impact of this new self-regulation mechanism.
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