Genetically encoded reporters and sensors for whole animal imaging using photo m...
Genetically encoded reporters and sensors for whole animal imaging using photo modulated Optoacoustics
In vivo imaging of cellular localization and function and visualization of the chemicals that drive life are key challenges for biological research. Current methods limit our insight into this bigger picture to either a glimpse (l...
In vivo imaging of cellular localization and function and visualization of the chemicals that drive life are key challenges for biological research. Current methods limit our insight into this bigger picture to either a glimpse (low penetration and small field of view) or a coarse overview (low resolution).
Optoacoustic (OA) imaging has the physical means to overcome these limitations, but it lacks the necessary toolbox of genetically encoded reporters and sensors that allow specific probing of localizations and distributions. So far, all efforts to create such a toolbox were impeded by the strong tissue background inherent to OA. Recently, exploiting my longstanding expertise in reversibly switchable reporters I overcame this hurdle by introducing the concept of photo-modulation to OA. Switchable reporters allow modulation of the reporter signal to separate it from the background – making the latter virtually invisible (Switch2See). In parallel, the concept was used by a U.S. consortium in vivo, underpinning its validity.
Hence, now is the time to combine my expertise in switching, protein-engineering, sensors, and OA imaging to create a toolbox that will allow to follow cells over time, visualize their interactions, and image the distributions of chemicals – all on the scale of the whole live organism with resolutions of 20 - 150 µm. With Switch2See, I will lay the foundations by building dedicated screening infrastructure, use it to develop a range of reporters (multiplexing) and sensors, and develop algorithms to convert the photo-modulation patterns into images. I will demonstrate the revolutionary impact on whole-animal imaging by visualizing localization, dynamics and interaction of immune cells in the tumor micro-environment (TME) and visualize aspects of its chemical heterogeneity. Beyond cancer research, this will impact all questions requiring a bigger picture – from developmental processes over neurobiology to the functioning of the immune system.ver más
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