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Controlling protein activity by ultrasound

PhD ceremony:Y. Zhou, BSc
When:March 07, 2023
Supervisor:prof. dr. A. (Andreas) Herrmann
Co-supervisor:dr. P. (Patrick) van Rijn
Where:Academy building RUG
Faculty:Science and Engineering

Ultrasound has shown its superior advantages in remote controlling protein activity with a high spatiotemporal resolution in vivo. Some other external stimuli can achieve this, such as light and magnetic fields, but with a few limitations. For instance, the most researched light has a naturally constrained low penetration depth in optically dense samples such as tissue, alongside its potential phototoxicity. In contrast, ultrasound can penetrate more deeply into such optically dense samples or even the whole skull and is widely used for biocompatible clinical imaging and therapy. Thus, remote control over protein function and cellular activity by ultrasound opens up a new field of study, which is termed sonogenetics. However, the existing research on sonogenetics is mainly based on the mechanosensitive channels and the possibility of controlling the activity of the non-channel protein by ultrasound has rarely been explored. Inspired by the principles from the polymer mechanochemistry field that ultrasound can control the properties of the interested polymer at the molecular level through site-specific rearrangement or bond cleavage, here this content investigates to control of the non-channel protein activity using ultrasound by two strategies: 1) inserting a supercharged elastin-like polypeptide domain into protein structure to increase its sensitivity towards ultrasound.; 2) loading the thrombin into a rolling cycle replication synthesized DNA gel, which can release thrombin under biomedical focused-ultrasound applications as a trigger to initiate the split-intein splicing reaction.