Immunology, Transplantation and Infectious diseases

Biocrystallography

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Head of Unit

Massimo Degano

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The activities in the Unit are aimed at clarifying the relationship between the function and the three-dimensional structure of biological macromolecules such as proteins, nucleic acids, polysaccharides, lipids, and their complexes.

The unit study macromolecules that are central in basic processes of cellular life, as well as for specific human pathologies. Starting from highly purified samples, researchers apply an array of biophysical techniques that include X-ray crystallography and cryo-electron microscopy to achieve high-resolution information on their structure. The structural analysis guides further mutagenesis and biochemical experiments in both reconstituted systems in vitro and in primary cells, to finely analyze the mechanisms that mediate macromolecular function, or lead to a pathological dysfunction. This multidisciplinary analysis provides the blueprint for a detailed understanding of complex biological processes, the pathogenic mechanisms leading to diseases such as cancer, autoimmune or genetic diseases. The high resolution structures are the starting point for the design of lead compounds that are endowed with high specificity, and can undergo further development for the design of highly specific, personalized drugs.

Research activity

Current projects include the study of the molecular mechanism underlying the onset of Chronic Lymphocytic Leukemia, with the ultimate goal of developing compounds that antagonize the pathogenic B-cell receptor-mediated signal, specific for each subgroup of patients.

A second line of research focuses on the aspects of G- protein coupled receptor-mediated signals in the therapy of Multiple Sclerosis. The unit is studying the molecular aspects of the binding of fingolimod to the sphingosine 1-phosphate receptor family members, in order to fully appreciate the ligand features that induce the therapeutic effect.

Moreover, the unit is exploring the possibility to develop new ligands specific to orphan GPCRs to induce a remyelination process in damaged CNS and PNS.