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.

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Revealing 3D anatomy with lightsheet microscopy

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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.
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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.

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Expansion microscopy

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."

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Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL

Available resources

We are always looking for innovative collaborations to advance the techniques, hardware and software related to ALICe.

Director of Neuroimaging: Stéphane Pagès, PhD

Microscopy Facility Manager: Laura Batti, PhD

If you would like to find out more, please contact us: microscopy@wysscenter.ch

A section of human cerebellum from the Lamylab at the University of Geneva imaged with the Wyss Center’s mesoSPIM lightsheet microscope. The image shows blood vessels labelled with the marker lectin. Blood supplies energy to the brain and is known to be disregulated in some diseases. Imaging brain vasculature with advanced microscopes helps drive research into neurodegenerative diseases and stroke. Credit: Tomàs Jordà – Lamylab, University of Geneva – Human Brain Mapping project
3D image of intestinal villi. Villi are controlled by the enteric nervous system (ENS) our gut’s own little brain. The team is using the three-dimensional microscopic imaging of the intestinal wall to better understand the involvement of enteric neurons in gut function and their connection with the brain. Image acquired with Clarity Optimised Lightsheet Microscope. Gut section cleared with iDisco+ protocol. Data are processed with a depth coding algorithm – the color represents the depth of the 3D image.
This image of virally labelled neurons in the brain helps reveal the cellular connectivity between the entorhinal cortex and hippocampus. These two regions are involved in memory processing and play a crucial role in the study of neurodegenerative disorders. Image courtesy of Noémie Mazaré, Giovanni Carriero, Roberta de Ceglia, Laura Solanelles, Bilian Xiong, Prof. Ludovic Telley and Prof. Andrea Volterra at the University of Lausanne.
Brain wide labelling of glutamatergic projection neurons – Courtine Lab, EPFL

Thy1 GFP, mouse – Holtmaat Lab, University of Geneva

Fluorescent interneurons in a whole brain – Fhyn Lab, University of Oslo

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Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL

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Fluorescent interneurons in a whole brain – Fyhn Lab, University of Oslo

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Heart innervation, Chatelier Lab – University of Poitiers



Laura Batti, PhD

Microscopy Facility Manager

Stéphane Pagès, PhD

Director of Neuroimaging

Yoseline Cabara, PhD

Microscopy Scientist

Ivana Gantar, MSc

Advanced Microscopy Imaging Specialist

Corinne Brana, PhD

Neurobiology Lab Manager

Jules Scholler, PhD

Photonics and Software Engineer

Grégoire Courtine, PhD

Collaborator, EPFL

Anthony Holtmaat, PhD

Collaborator, UNIGE

Christophe Lamy, MD, PhD

Collaborator, UNIGE

Christian Luscher, MD, PhD

Collaborator, UNIGE

Mackenzie Mathis, PhD

Collaborator, EPFL

Nicolas Renier, PhD

Collaborator, Paris Brain Institute

Valérie Dutoit, PhD

Collaborator, UNIGE
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Wyss Center


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