Broad Institute Inc.
Neuropsychiatric diseases arise from a combination of genetic and environmental factors that influence the molecular, morphological and physiological properties of neurons and glia in the brain. Elucidation and treatment of these diseases will benefit from understanding how specific brain cell types connect and signal in neural circuits, and how genetic factors affect their cellular function. Transgenic techniques have been widely used to target specific cell populations with fluorescent reporter (e.g. GFP) and modulator (e.g. channelrhodopsin-2) genes to probe their role in disease mechanisms. However these conventional gene targeting strategies depend on the identification of unique molecular markers and promoters and are largely limited to the mouse, whereas other animal models that are commonly used for neuroscience and disease studies (e.g. rats and primates) are still mostly inaccessible. Additionally, since many non-rodent animal models have long reproductive cycles, fundamentally new approaches for cell-type specific gene targeting are highly desirable. The researchers propose to develop and apply a generalizable genetic circuit for detecting endogenous transcription states to enable conditional genetic manipulation of specific cell types. The proposed technology could have broad applications for both disease research as well future therapeutic interventions.
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