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Antibody Engineering & Therapeutics Europe
6 - 8 June, 2023
Postillon Hotel AmsterdamDigital Experience: All Sessions Live-streamed 6-8 June, 2023

Luca Varani, PhD
Structural Biology Group Leader at Institute for Research in Biomedicine

Profile

Luca Varani graduated in chemistry (University of Milan, Italy) and obtained a PhD degree at the prestigious MRC-Laboratory of Molecular Biology (University of Cambridge, UK) using molecular and structural biology to study RNA-protein interactions in regulation of gene expression at the post-transcriptional level, culminating in the largest protein-RNA structure determined by NMR at the time (Nat. Struc. and Mol. Biol) and showing the role of RNA structure in mis-regulation of splicing leading to dementia (PNAS). Postdoc at Stanford (USA) with a long term EMBO fellowship, he used, for the first time, high-resolution NMR to study TCR/pMHC complexes, key proteins of the immune system (PNAS).Since October 2007 he leads the Structural Biology group of the Institute for Research in Biomedicine (Bellinzona, CH). The group strives to understand the molecular properties allowing a given antibody to eliminate a pathogen, using this information to engineer new antibodies with desired properties. NMR and other experimental information are used to validate computational simulations aimed at determining the structure and function of antibody-antigen complexes. Studies involve mainly rare and neglected diseases such as Dengue or Zika virus, Prion or rare form of Leukemias and, more recently, COVID-19.Last authorship for design and characterization of bispecific antibodies against SARS-CoV-2 (Nature), Zika (Cell) and Prion (Plos Path.) as well as describing the role of target affinity modulation in Chimeric Antigen Receptors (Mol. Therapy). Collaborative work to determine the antibody response to infection in Dengue (Cell Host and Microbe), Zika (Science) and malaria (Nat Med) plus characterization of neutralizing antibodies in MERS (PNAS). The potently protective SARS-CoV-2 and Zika bispecifics demonstrated the ability to react timely and swiftly to epidemic events. The prion bispecific is peculiar since a neurotoxic antibody was fused to a second one to obtain a bispecific that potently protects from prion toxicity even if administered when signs of neurodegeneration are already evident. Shorter term collaborative work included characterization of intermolecular interactions in cytokines (J.Ex.Med), nanoparticles (Small) and autophagy (Nat Cell Biol). Other projects involved rational engineering of protein and antibodies, combining structural insights with computational simulations to increase potency and alter selectivity. The group uses a highly multidisciplinary approach, varying from structure determination to cellular experiments, from computational biology to protein and antibody production and engineering, from nanoparticles to confocal microscopy. It is one of the very few groups with high impact publications attesting the ability to approach antibody-pathogen interactions both experimentally and computationally.

Agenda Sessions

  • Human Bispecific Antibodies against Infectious Diseases

    14:45