Projects
From chemical biology to neuroscience
We take a multidisciplinary approach—combining protein engineering, bioorganic and peptide chemistry, molecular biology, biochemistry, biophysics, and cellular imaging—to study the dynamics of protein assemblies involved in neuronal cell organization and function. Our goal is to create methods and tools that reveal how neuronal proteins interact and how these interactions are regulated under physiological conditions or disrupted in disease. Focusing on protein–protein interactions (PPIs), we pursue two main strategies: modulation and monitoring.
For modulation, we design biomolecules that can precisely control specific protein interactions in living systems, often using light to achieve high spatial and temporal resolution. For monitoring, we develop advanced observation tools—leveraging chemistry and protein engineering—to improve probe properties such as size, dye nature, and valence in step with advances in imaging technologies. We also use these tools to map the molecular architecture of target complexes and identify the key elements that govern their regulation
BIOMIMETIC LIGANDS
We design biomimetic peptide ligands using structural and biological data to mimic key features of synaptic protein complexes, such as AMPA and NMDA receptors, and their interactions with scaffold proteins like PSD-95. These ligands, often incorporating multiple PDZ domain-binding motifs, are used to acutely disrupt specific endogenous interactions and serve as tools in structural, biophysical, and interactomics studies to better understand complex protein–protein interactions.
PHOTOCONTROL OF PPIs
Light provides a powerful approach to achieve high spatial and temporal precision over the effect of a given active molecule when using a photoactivatable or “caged” derivative of that same compound. With the general aim of improving the properties and expanding the range of application of our tools, we develop methods to incorporate and exploit light-sensitive elements (synthetic or protein-based) with the ligands that have been previously validated as efficient PPI modulators or protein binders.
DIRECTED EVOLUTION OF PPI MODULATORS
As an alternative to the rational design of peptide-based ligands, we are also developing directed evolution approaches using a phage-based strategy in order to generate small protein domains that are selected for their capacity to efficiently recognize specific domains or PPIs. These tools are ultimately exploited for modulation and imaging purposes..
MOLECULAR TOOLS FOR IMAGING
In parallel to the fast improvement of super resolution imaging techniques, there is a growing need for generic protein labeling tools and methods that take advantage of the resulting gain in resolution. In this context, we combine chemical-based approaches and protein engineering in order to develop innovative tools to address the current limitations associated with the existing probes (such as the size, the valence and the nature of the dyes).
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