We develop technologies to image and control the function of cells deep inside the body. These technologies take advantage of biomolecules with unusual physical properties allowing them to interact with sound waves and magnetic fields. We apply these tools to problems in synthetic biology, neuroscience, cancer, immunology and the mammalian microbiome.
Can we use ultrasound to remote-control the location and motion of specific cells? Yes! We show that gas vesicles are exceptionally good “acoustic antennae”, experiencing strong acoustic forces relative to their nm size. In ultrasound gradients, GVs and cells expressing them get pushed more strongly – and in the opposite direction – from other biological materials. As a result, we can selectively push them, trap them, pattern them and sort them selectively under acoustic remote control. Congratulations to Di and colleagues on this foundational advance in acoustic actuation and sonogenetics.
Wu D, Baresch D, Cook C, Duan M, Malounda D, Maresca D, Abundo MP, Lee J, Shivaei S, Mittelstein DR, Qiu T, Fischer P, Shapiro MG*. Biomolecular actuators for genetically selective acoustic manipulation of cells.Science Advances 9, eadd9186 (2023). article | press | video
The first generation of acoustic reporter genes proved a concept but were insensitive, burdensome and impossible to image continuously. Welcome ARGs 2.0! These new reporter genes provide much greater sensitivity, nonlinear ultrasound contrast, and ease-of-use for expression in a variety of cell types. Congrats to Rob, Marjorie, Tom and colleagues on this major advance! Constructs for mammalian cells and bacteria available on Addgene.
Hurt RC#, Buss MT#, Duan M#, Wong K, You MY, Sawyer DP, Swift MB, Dutka P, Barturen-Larrea P, Mittelstein DR, Jin Z, Abedi MH, Farhadi A, Dephande R, Shapiro MG*. Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria.Nature Biotechnology (2023). article
How do you make a protein that self-assembles, fills with air, excludes water and withstands several atmospheres of pressure? A century-old mystery for Gas Vesicles. Congratulations to Przemek and colleagues in the Shapiro and Jensen labs on figuring this out with a beautiful CryoET structure.
Dutka P, Metskas LA, Hurt RA, Salahshoor H, Wang TY, Malounda D, Lu GJ, Chou TS, Shapiro MG*, Jensen GJ*. Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET. Structure (2023). article
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Can we activate the production of immunotherapy drugs specifically inside solid tumors? Yes, by engineering gene circuits in tumor-homing bacteria to take commands from thermal focused ultrasound. Congratulations to Mohamad, Michael and collaborators on this new paper demonstrating the local delivery of checkpoint inhibitors inside solid by ultrasound-controlled probiotic agents.
Abedi MH#, Yao M#, Mittelstein DR, Bar-Zion A, Swift MB, Lee-Gosselin A, Barturen-Larrea P, Buss MT, Shapiro MG*. Ultrasound-controllable engineered bacteria for cancer immunotherapy. Nature Communications 13, 1585 (2022). article | press
Focused ultrasound excites cortical neurons by opening specific mechanosensitive ion channels, leading to gradual calcium accumulation, activation of calcium-gated channels, depolarization and spiking. Congratulations to Sangjin and collaborators on this detailed biophysical study.
Yoo S, Mittelstein DR, Hurt RC, Lacroix JJ, Shapiro MG*. Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification.Nature Communications 13, 493 (2022). article
Congratulations to Avinoam and colleagues on showing that cells can be engineered to migrate into tumors and damage them from the inside upon receiving a focused ultrasound stimulus. Their new paper establishes gas vesicles as genetically encoded seeds for inertial cavitation, bringing together cellular and physical therapy.
Bar-Zion A, Nourmahnad A, Mittelstein DR, Shivaei S, Yoo S, Buss MT, Hurt RC, Malounda D, Abedi MH, Lee-Gosselin A, Swift MB, Maresca D, Shapiro MG*. Acoustically triggered mechanotherapy using genetically encoded gas vesicles.Nature Nanotechnology 16, 1403–1412 (2021). article | readcube