Quantitative imaging of the cell

General objective

We develop innovative labeling, imaging, and analytical methodologies to unravel the organization and dynamics of proteins across a range of cellular models and spatial scales. Our work is centered on quantitative single-molecule localization microscopy (SMLM), single-particle tracking (SPT), light-sheet fluorescence microscopy (LSFM), and high content screening, with a strong emphasis on their applications in cell biology and neuroscience.

Microscopy Development and Applications

We design and build advanced microscopy setups, develop specialized labeling strategies, and create analytical tools to quantify protein organization at the nanoscale. A significant contribution from our team is the development of single-objective light-sheet microscopy (soSPIM). soSPIM provides efficient optical sectioning and enables in-depth high- and super-resolution imaging of in vitro cellular models, ranging from isolated cells to complex 3D culture systems such as spheroids and organoids. Complementing this, we implement multi-color labeling approaches using orthogonal probes to sequentially image multiple proteins.

More recently, we have further refined the soSPIM technology to support high-content monitoring of 3D cell cultures, paving the way for its use in drug screening and functional assays.

Data Analysis and AI Integration

Our primary achievements are rooted in model-based image analysis and advanced geometry processing, which have enabled precise quantification of complex biological structures. Building on this expertise, we are now actively exploring how deep learning approaches can drive further breakthroughs in both the acquisition and analysis of microscopy data, aiming to push the limits of high-resolution and high-throughput imaging.

Biological Applications

Over the past 15 years, we have effectively integrated single-molecule nanoscopy, customized image analysis pipelines, and advanced labelling and bioengineering strategies to tackle fundamental questions in neuroscience and cell biology. With the recent incorporation of O. Thoumine, our research is now increasingly directed toward developing neuronal 3D models to investigate synapse formation and communication, leveraging the unique capabilities of our soSPIM technology.

Technology Transfer and Open Science

We maintain a strong commitment to both academic and industrial technology transfer. Our team develops software tools and microscopy solutions, which we actively disseminate through a variety of channels, including scientific publications, patents, industrial collaborations, academic material transfer agreements, and collaborative or open-source initiatives. This approach ensures that our innovations not only advance fundamental research but also translate into broader scientific and technological impact.

Team organization

The Quantitative Imaging of the Cell team is an R&D group that brings together experts from diverse disciplines, including microscopy, computer science, and biology. This multidisciplinary foundation enables us to address complex research questions with a holistic and integrative approach.

Members (permanent)

Jean-Baptiste Sibarita (IRHC CNRS, IINS) is the team leader since 2009. Physicist by training, he has expertise in quantitative microscopy and image analysis applied to neuroscience and cell biology.
Rémi Galland (CRCN CNRS) is a physicist, with an expertise in optics and super-resolution microscopy. He is the main developer of the soSPIM technology.
Florian Levet (IRHC INSERM) is a computer scientist, with a strong expertise in image analysis applied to microscopy. He is the main developer of several popular software (SR-Tesseler, PoCA) for single molecule localization microscopy data and deep learning.
Olivier Thoumine (DR1 CNRS) joined the group in Jan. 2024, after heading the team “Cell Adhesion Molecules in Synapse Assembly” for 14 years at IINS. He is internationally recognized for his work on the function of cell adhesion complexes in synapse differentiation, combining biomimetic assays, single molecule imaging, biophysical models, and optogenetics.

Keywords

Single Molecule Localization Microscopy ; Single Particle Tracking, ; Single objective Light-Sheet Fluorescence Microscopy ; High Content Screening, Bioimage Analysis ; Geometry Processing ; Deep Learning ; 3D cellular models ; Protein Labelling ; Synapse ; Neuroscience