State-of-the-art advanced lightsheet imaging center
Lightsheet microscopes can reveal the 3D anatomy of entire small organs. They image brain tissue down to individual neurons and offer unprecedented maps of nervous system structure and function.
ALICe, the Advanced Lightsheet Imaging Center, integrates a series of innovative fluorescence microscopy tools in a single pipeline to image whole organs with custom-built microscopes at high spatial and temporal resolution.
Revealing 3D anatomy with lightsheet microscopy
3D spatial transcriptomics: Discovering new sub-cellular worlds in 3D brain samples
The multidisciplinary ALICe team unites expertise from physics, cell biology, neuroscience and engineering, and joins forces with research teams around the world to image and draw insights into the central and peripheral nervous systems, innervation of organs including the brain and heart as well as human brain samples. Another focus area is brain and spinal cord organization for researchers working to restore movement after paralysis or to investigate neuronal networks involved in cognition, pleasure and drug addiction.
Unlike traditional microscopy in which specimens are cut in slices with a blade before being viewed on a slide under a microscope, lightsheet microscopes optically slice samples with a sheet of light. This optical sectioning captures slivers of image without damaging the sample. The images are then combined to reconstruct a detailed three-dimensional image of a whole organ or specimen.
The ALICe pipeline
ALICe’s capabilities cover the entire pipeline, from sample preparation to image capture and post-processing. A variety of samples can be imaged from organoids to whole organs, labelled with genetically encoded fluorescent proteins or immuno-labeled with fluorescent antibodies.
1) Sample preparation: Tissue clearing for entire large samples
2) Custom-built lightsheet image acquisition: high spatial and temporal resolution imaging
3) Image and data analysis including 3D data-set exploration in virtual reality
Creating elastic brains
To image brain samples, fluorescent tags are used so that structures are visible with a microscope. To help these tags penetrate thick samples, the team is exploring a new method - ELAST (entangled link-augmented stretchable tissue-hydrogel). They embed the sample in an elastic polymer gel that allows it to deform and reshape. Then they stretch the sample over hundreds of cycles while it bathes in a solution of antibodies. The process makes labeling of thick samples more efficient.
Chemical anchors in expanding gel attach to biomolecules, physically expanding the brain sample and allowing as much information as possible to be extracted from the tissue. Expansion microscopy deepens our understanding of disease mechanisms to accelerate development of therapies for neurological and psychiatric disorders, like Parkinson’s and Alzheimer’s diseases.
Prof. Holmaat, Unige"Recent advances in microscopy have propelled the neurosciences into the era of connectomics, now allowing us to study single neurons with their synaptic connections in the whole brain."
Prof. Daniel Huber, Unige"The work at ALICe allowed us to reveal the distribution and anatomy of sensory receptors with unprecedented resolution and specificity. I was stunned by the quality of the images."
Prof Fyhn - UiO"Never before have we been able to visualise and quantify, in-depth, neuronal populations within the entire brain as we can now."
Clearscope Light-sheet MBF
Olympus VS120 Automated Slide Scanner
TissueScope - Huron Digital Pathology
Eclipse Ti2-U - Nikon
Confocal LSM880 + Airyscan - Zeiss
Confocal - Spinning Disk CSU-W1
Nikita Vladimorov - University of Zurich
New project: Repairing the spinal cord
Gene therapy to boost rehabilitation success following spinal cord injury.Collaboration
New project: STAR - Solutions Through Astrocyte Research
The STAR team is pursuing new strategies, focused on astrocytes, to identify biomarkers and new therapeutic targets to treat neurological and psychiatric disorders.Wyss Center
In conversation with Jules Scholler, PhD, Software Engineer in Bioimaging
Software Engineer in Bioimaging, Jules Scholler, describes what it's like to work at the boundary of biology, optics and computer science. The ‘in conversation’ series features members of the Wyss Center community discussing their work, their collaborations and imagining the future.Insight