Luca Varani graduated in chemistry at the 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. He contributed to show the key role played by RNA in regulation of gene expression and how RNA itself can be a valid therapeutic target against dementia. His numerous high caliber publications, culminated in the determination of the largest NMR structure available at the time, allowed him to move to Stanford with a “long term EMBO fellowship”, reserved to the best young molecular biologists in Europe. In California Luca Varani completed the first magnetic resonance study on TCR/pMHC, key proteins of the immune system.
Since October 2007 he leads the Structural Biology group of the Institute for Research in Biomedicine (Bellinzona, CH). The main activity involves the characterization of interactions between pathogens and antibodies, molecules of the immune system capable of curing and protecting from illness. The group tries to understand the molecular properties that allow a given antibody to eliminate a pathogen. Studies involve mainly rare and neglected diseases such as Dengue or Zika virus, Prion or rare form of Leukemias. The NMR approach developed at Stanford was pushed forward at the IRB, where computational techniques allow discovering which part of the pathogen is recognized by antibodies. Experimentally guided and validated computational simulations yield the atomic three-dimensional structure of antibody/pathogen complexes. The approach allowed to rationally modify an existing antibody, increasing its ability to neutralize Dengue virus by 50 fold utilizing, for the first time, only computational tools. They also performed one of the rare NMR studies showing how antibody binding alter the local flexibility of the antigen.
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 synthesis of nanoparticles to confocal microscopy.
Our group uses computational, biochemical and biophysical tools to determine the three-dimensional atomic structure of proteins and characterize their interactions with other molecules, with particular attention to antibody-antigen interactions in infectious diseases.
The final goal is to understand the molecular properties that make a given antibody effective against a pathogen, and eventually to exploit this knowledge to design new drugs against diseases such as Dengue and Zika, Prion or some rare form of Leukemia. Dengue and Zika are tropical viruses in rapid expansion whereas Prion, famous in the 90s due to the Mad Cow scare, causes a neurodegenerative disease with no cure and still largely unknown. Understanding which part of the pathogen is recognized by the most efficient antibodies allows discovering and blocking of the key parts of the pathogen itself.
Our group has a highly multidisciplinary approach that merges biochemical data, experimental structural information and computational simulations. Computational Structural Biology, in particular, is a rapidly developing and increasingly important field. At this time, however, computational predictions are not always accurate; it is therefore crucial to guide and validate them with experimental data. The synergy between computational simulations and classic biophysics, molecular and cellular biology combines the best of both approaches: the low cost and high speed of computers with the rigorous and reliable experimental validation. It is common opinion among scientists that future biomedical sciences will require a combination of computational and experimental techniques.