Sonogenetics: remote modulation of gene expression by ultrasound
Abstract
Optogenetics, based on light as a spatially and temporally defined signal, made powerful impacton life sciences and has enabled precise activation of neurons and control of transcriptionalresponses. Ultrasound (US) can also be programmed and focused, and in contrast to light it canpenetrate deep into tissues, potentially enabling remote control of cells with exciting possibilitiesfor therapeutic and technological applications and understanding of the mechanisms ofmechanosensing.We aim to develop the foundations of sonogenetic technology, based on the enhancement ofmammalian cell sensitivity to US and other mechanical/tactile stimuli, which will be coupled tothe activation of cellular signaling pathways towards transcriptional control of selected genes.We propose to enhance the response of mammalian cells to US or other mechanical stimuli byexpressing self-assembling bacterial protein gas vesicles (e.g. Gvps) that are naturally producedin floating aquatic bacteria. The compressibility of gas-filled protein vesicles expressed withinthe mammalian cell cytoplasm is expected to amplify the mechanical and acoustic stress on thecellular cytoskeleton and membranes and enhance activation of mechanosensitive channels.Furthermore, a positive feedback loop to enhance calcium influx to a sufficient level to triggeractivation of the selected gene transcription will be introduced. The calcium influx throughmechanosensitive ion channels will be coupled to the designed transcriptional regulation cascadebased on the engineered NFAT (nuclear factor of activated T cells) transcription factor to targetthe selected genes based on fused DNA targeting domains. Successful project will enable remotecontrol of cells using noninvasive US stimulation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 19, 2020
- Source ID
- N629092012090
Entities
People
- Roman Jerala
Organizations
- Office of Naval Research
- United States Navy