The Molecular Engineering for Health Unit (SIMoS) conducts research focused on: (I) the development of innovative molecular tools to investigate proteins involved in various pathophysiological processes; (II) the design and optimization of next-generation antibodies with enhanced developability and reduced immunogenicity; and (III) the identification and preclinical development of bioactive compounds derived from natural sources with diagnostic and therapeutic potential.
We develop broad-spectrum inhibitors that target bacterial toxins by disrupting the host cell's intracellular trafficking machinery. By modulating these pathways, our compounds also exhibit antiviral, anti-intracellular bacterial and anti-parasitic activities. Our work also includes the design of a fragment of the diphtheria toxin as an inhibitor of HB-EGF for the treatment of crescentic glomerulonephritis, a rare kidney disease.
We develop innovative technologies at the interface of chemical biology, medicinal chemistry, chemoproteomics, molecular imaging, and nanomedicine to study proteins in complex biological systems. Our research focuses on the development of diagnostic and therapeutic tools targeting chronic inflammatory diseases, fibrosis, cardiovascular diseases, autoimmune disorders, and neurodegenerative diseases.
The team develops novel antibody-based ligands for a range of applications, including therapeutic, imaging, and diagnostic purposes. It focuses particularly on designing high-affinity antibodies with controlled selectivity and low immunogenicity, enabling administration in humans while minimizing the risk of immune responses.
Our team combines biomolecular engineering, synthetic biology, and generative artificial intelligence (AI) to design innovative biological systems and proteins. Our approach integrates high-throughput methods (multiplexed assays of variant effects, MAVE; NGS) and proprietary technologies such as in vitro DNA assembly (SLiCESBE) and bacterial genome engineering.
- Immunogenicity of proteins and antibodies (Bernard Maillère)
Our studies focus on identifying the sequences recognized by CD4 T cells (T-cell epitopes), characterizing the clonality of T cell repertoires specific to therapeutic proteins, defining the effector or regulatory phenotype of CD4 T cells specific to therapeutic proteins, and developing strategies to generate de-immunized molecules, i.e., molecules that no longer induce immune responses.
Our research activity focus on the discovery, synthesis, pharmacological characterization, engineering and in-vivo preclinical evaluation of natural peptides and phycotoxins, with the aim of developing innovative therapeutic and diagnostic agents. In particular, we investigate venom-purified and endogenous peptides, as well as marine phycotoxins targeting G Protein-Coupled Receptors (GPCRs) and ion channels, given the central physiopathological roles of these molecular targets. In parallel, we conduct molecular and cellular neuroscience studies aimed at deciphering the mechanisms underlying Aβ1-42 oligomerization.