Julien CAPIN (invité équipe 1)
Accelerating the Discovery and Evolution of De Novo Protein Binders with Cell-Free Systems
Jeune chercheur au Centre de Biologie Structurale (CBS) de Montpellier.
Équipe "Synthetic Biology" - Jérôme Bonnet
Computational protein design is transforming our ability to generate protein binders for a wide range of biomedical and biotechnological applications. However, experimental screening and characterization remain major bottlenecks, limiting the speed and accessibility of binder discovery. We recently developed Cell-Free Two-Hybrid (CF2H), a rapid and sensitive platform for detecting protein–protein interactions without the need for cloning, protein purification, or specialized laboratory equipment [1]. In this talk, I will discuss how CF2H accommodates diverse binder formats, including single-domain antibodies, DARPins, and de novo designed proteins, and how we applied it to therapeutically relevant targets such as immune checkpoints (PD-L1, PD-1) and a CAR-T-relevant receptor (IL-1RAP). Since rapid screening facilitates iterative design-build-test cycles, we also harnessed our system for AI-guided affinity maturation, yielding up to 25-fold affinity improvement over the parent design in a single round. I will close with our ongoing work extending this pipeline from human receptors to microbial virulence factors, focusing on aerolysin, a bacterial pore-forming toxin recently linked to susceptibility to ulcerative colitis [2].
