Research Group: Maria Enrica Tira, Claudio Seppi, Laurent Chiarelli

1) Functional role of the matrix extracellular molecules. The research conducted in the Laboratory of the Extracellular Matrix is focalized on the study of interactions of small proteoglycans (decorin, fibromodulin and biglycan) with fibrillar collagens (type I and II). In addition to this study our group investigates the functional interactions of some extracellular macromolecules (fibronectin, collagen peptides, small proteoglycans) with platelets and megakaryocytes.

2) Purification and characterization of mutant forms of gamma-glutamyltranspeptidases (GGTs) of B. subtilis. Bacterial GGTs are of biotechnological interest being useful in food, pharmaceutical and chemical industries. GGTs use different substrates, from low molecular weight molecules, to large polymers as poly-gamma glutamate (PGA). PGA is produced by several bacteria as a protection against antimicrobials produced by their hosts. However, not all GGTs are able to hydrolyse PGA. To elucidate the amino acid sequences necessary to let the GGTs to hydrolyse PGA, we are using mutant forms of GGT from B. subtilis.

3) Characterization of bacterial enzymes as targets of antimicrobial drug. The research aim to identify novel antibiotics against two pathogens: M. tuberculosis and B. cenocepacia, through target-to-drug strategies. With this purpose, the potential targets, emerged from compound libraries screening, are produced to characterize the mechanism of action of the identified inhibitors. Moreover, these enzymes are exploited for drug design to implement the activity of the inhibitors and to design novel compounds. The research is focused, on two targets of the two bacteria: quorum sensing synthase CepI and glutamate racemase.

Recent Publications:

• Abbonante V, Gruppi C, Catarsi P, Avanzini MA, Tira ME, Barosi G, Rosti V,Balduini A. Altered fibronectin expression and deposition by myeloproliferative neoplasm-derived mesenchymal stromal cells. Br J Haematol. 2016, 172:140-4.
• Esposito M, Szadocka S, Degiacomi G, Orena BS, Mori G, Piano V, Boldrin F,Zemanová J, Huszár S, Barros D, Ekins S, Lelièvre J, Manganelli R, Mattevi A, Pasca MR, Riccardi G, Ballell L, Mikušová K, Chiarelli LR. A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors. ACS Infect Dis. 2017, 3:428-437.
• Israyilova A, Buroni S, Forneris F, Scoffone VC, Shixaliyev NQ, Riccardi G, Chiarelli LR. Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. PLoS One. 2016, 11:e0167350.