Medical Engineering Thesis Defense, Zhiyang Jin

Zoom: https://caltech.zoom.us/j/8117004263

Noninvasive observation of molecular processes in living organisms represent a "holy grail" for biomedical research. The most widely used fluorescence imaging approaches with genetically encoded biosensors have enabled major discoveries, but implementing them in vivo could be challenging due to the physical limitation of light scattering. Alternatively, ultrasound has unique advantages as a modality for noninvasive imaging due to its ability to penetrate deeper (several cm) while providing good spatiotemporal resolution (~ 100 µm and ~ 1 ms) and large imaging volume (~ cm3). However, it was historically difficult to connect ultrasound as an oscillating mechanical wave to biology at the molecular scale. Our work attempts to bridge this gap by engineering ultrasound-interacting biomolecules. In this talk, I will share with you our recent development of the genetically encoded acoustic biosensors based on gas vesicles (GVs) - a unique class of air-filled protein nanostructures derived from buoyant microbes. These biosensors couple dynamic molecular activity to ultrasound contrast through their engineered surface proteins which can change GVs' acoustic properties upon sensing specific analytes. In particular, I will walk you through our journey to develop the first-ever acoustic biosensors and apply them for sensing enzyme activity and calcium dynamics inside living cells. I will show you that now we can noninvasively image protease activity in probiotics in the mouse GI tract and "see" receptor-mediated calcium signaling deep in the mouse brain through the intact skull. At the end of my talk, I will also touch on our efforts to accelerate the engineering of these acoustic biomolecules through the combination of ultrasound instrumentation and synthetic biology. Taken together, I hope to convince you that biomolecular ultrasound would lead to an exciting future.