Probing the mysteries of sweet “on-off” switches of the human immune system: toward the development of novel glycomimetics against bacterial infections

ongoing

Glycans are directly involved in the normal physiology and in the etiology of several major diseases, spanning from bacterial and viral infections through to cancer and autoimmune disorders. Thus, deciphering the glycome holds huge promise to provide new targets and diagnostics for human health. Despite the tremendous advance of knowledge in the field of Glycoscience during the last decade, the comprehension at high resolution of the molecular basis of many pathogen-mediated diseases is still incomplete. GLYCOSWITCH will significantly contribute to fill this gap, providing a holistic picture of the manifold mechanisms of host responses to microbial infections, with a special focus on Gram-negative bacteria. I propose to address bacterial glycans recognition by host immune proteins by using a multidisciplinary approach, combining state-of-the-art synthetic organic chemistry, molecular biology, biochemistry and biophysics techniques, massively including NMR spectroscopy. I will apply them in an innovative integrated chemical biology approach in order to decipher key glycan recognition aspects beyond current knowledge. Understanding of molecular mechanisms of detection of invasive virulent bacteria by host organisms will allow to reach the ultimate goal of GLYCOSWITCH project: the design and development of novel and effective glycomimetics able to modulate the function of host immune receptor proteins. The success of GLYCOSWITCH will unlock attractive opportunities for the development of host-directed strategies to boost the immune response or reverse pathogen-induced immunosuppression. My unique approach to this project, as an organic chemist with wide expertise in NMR and bacterial glycans, will provide groundbreaking information on protein-glycan interaction systems of paramount importance in biology and biomedicine, opening new avenues for approaching bacterial diseases and their secondary effects.