Cinzia Calvio
Cinzia Calvio
affiliation: Università di Pavia
research area(s): Genetics And Genomics, Molecular Biology
Course: Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
Cinzia Calvio obtained her first degree cum laude in Biology from the University of Pavia in 1990. In 1993 she obtained the degree in Applied Genetics from the Specialization School in “Applied Genetics” at the University of Pavia. The Specialization thesis work was carried out at the IGM-CNR, in Pavia. She did her first postdoc at the European Molecular Biology Laboratory (EMBL), Heidelberg (D), and a second Postdoc at the European Institute of Oncology - IEO, Milan. She then moved to a commercial company as Product Specialist for automated DNA sequencers and instrumentation for analyses of macromolecular interactions. In 1999 she joined the Dept. of Genetics and Microbiology of the University of Pavia as supervisor of the departmental sequencing facility. In 2003 she joined, the lab of Microbial Genetics at the Dept. of Biology and Biotechnology of Pavia University as Assistant Professor in Genetics. After a long collaboration with Prof. A. Galizzi, from 2009 she is the PI of the Microbial Genetics Laboratory.
C. Calvio currently holds the chair of “Microbial Genetics” (in English) for the Master programme in Molecular Biology and Genetics. She is also involved in teaching Microbial biodiversity and genetics in soil at the Master program in Natural Sciences. Since 2004, she supervised 55 experimental theses for Bachelor, Master and PhD students. She acts as Academic Editor for PLOS One, is in the Board of Reviewers for Microbiology sgm and Applied and Environmental Microbiology and regularly acts as reviewer for several international journals (see Publon profile). She is member of the Microbiology Society and the European Federation of Biotechnology.
Her work has been funded by the Italian Ministry for University and Research (MIUR) (in 2003, in 2005 and in 2008 - For the latter project CC acted as PI/Coordinator); by the “Alma Mater Foundation” (2009); by the Lombardy Region-INSTM consortium (in 2009 and in 2013) and by the CARIPLO Foundation (two grants in 2015, one as PI; one grant in 2016; one grant in 2018).
The main research interest of the Microbial Genetics laboratory has been the regulation of stationary phase phenotypes in the model organism Bacillus subtilis. In particular, the lab characterized the swrA operon necessary for swarming, a specialized form of motility and identified the regulation driving the expression of swrA. We also demonstrated that the biosynthesis of the polymer poly-γ-glutamate (γ-PGA), with great biotechnological potentiality, depends on SwrA+DegU. Now the lab is working on the characterization of B. subtilis genetic circuitries and on engineering strains for different purposes.
The research activities are currently focused the following topics:
In Bacillus subtilis the two-component system DegS-DegU controls the expression of one hundred of genes involved in the exponential-to stationary phase of growth transition, coordinates single cells differentiation in multicellular communities and in pathogenic species, as Listeria monocytogenes or Bacillus anthracis, is involved in virulence. It has been shown that DegU regulates B. subtilis motility in a complex way. SwrA, a protein which has no similarity to previously characterized proteins, is also involved in such complex regulation. We have shown that there is a functional and molecular interaction between the two proteins, DegU and SwrA, in motility and now would like to extend our analyses to other genetic pathways DegU-regulated, as protease production. The aim is to identify the molecular signal that mediates DegSU two-component system activations and the to characterize DegU-SwrA interaction at the molecular level.
We recently characterized the activities of B. subtilis e E. coli GGTs and started the construction of mutant recombinant enzymes with altered enzymatic activity. With the support of the Cariplo Foundation we are now tailoring these enzymes for the synthesis of γ-glutamyl derivatives of naturally occurring and/or modified amino acids starting from bulk chemicals of biotechnological origin. The task of our unit is to obtain mutant GGT enzymes with enhanced activity and tailored for selected acceptor compounds. This work is in collaboration with Prof. C. Morelli (Dept. of Chemistry, Milan University).
Recently we characterized some Bacillus genes as encoding efficient and specific γ-PGA degrading enzymes. We determined that those gene are phage-derived and spread across bacteria through horizontal gene transfer. We also identified γ-PGA coding capacity in several microbial species, among which several pathogens. Currently, we are finely characterizing, both enzymatically and structurally, those hydrolases with the aim of exploring their potential as therapeutics for treatment of persistent infections caused by γ-PGA-producing pathogenic bacteria, in which the polymer acts as fundamental virulence factor.
γ-PGA is an anionic polymer produced by Bacilli that finds application in several biotechnological fields. For its full industrial exploitation, it is mandatory to reduce production costs, both increasing bacterial productivity and reducing fermentation costs either increasing its yield or decreasing fermentation costs. Our Lab has obtained a producer strain derived from the fully characterized B. subtilis lab strain. We are now applying genetic engineering to improve productivity and rationalize metabolic pathways for lowering fermentation costs. Currently our aim is to obtain a producer able to ferment organic components contained in some agro-industrial by-products.
• Effect of the inserted active-site-covering lid loop on the catalytic activity of a mutant B. subtilis γ-glutamyltransferase (GGT). 2019. Massone M., Calvio C., Rabuffetti M., Speranza, Morelli C.F. RSC Advances in press.
• Developing a Novel Enzyme Immobilization Process by Activation of Epoxy Carriers with Glucosamine for Pharmaceutical and Food Applications. 2019. Serra I., Benucci I., Robescu M.S., Lombardelli C., Esti M., Calvio C., Pregnolato M., Terreni M., Bavaro T. Catalysts 9:843. DOI:10.3390/catal9100843
• Integration of enzymatic data in Bacillus subtilis genome-scale metabolic model improves phenotype predictions and enables in silico design of poly-γ-glutamic acid production strains. 2019. Massaiu I., Pasotti L., Sonnenschein N., Rama E., Cavaletti M., Magni P., Calvio C. and Herrgård M.J. Microbial Cell Factories 18:3. DOI:10.1186/s12934-018-1052-2
• The structure of PghL hydrolase bound to its substrate poly‐γ‐glutamate. 2018. Ramaswamy S., Rasheed M., Morelli C.F., Calvio C., Sutton B.J., Pastore A. FEBS J. 285 (24), 4575-4589. DOI:10.1111/febs.14688
• Evidences on the role of the lid loop of γ-glutamyltransferases (GGT) in substrate selection. 2018. Calvio C., Romagnuolo F., Vulcano F., Speranza G., Morelli CF. Enzyme and microbial technology 114, 55-62. DOI:10.1016/j.enzmictec.2018.04.001
• Data for the synthesis of oligo-γ-glutamylglutamines as model compounds for γ-glutamyltransferases (GGTs) and for normalization of activities of different GGTs. 2018. Calvio C., Romagnuolo F., Vulcano F., Speranza G., Morelli CF. Data in Brief, 21, 576-581. DOI:10.1016/j.dib.2018.09.116.
• BioBrick™-Compatible Vector for Allelic Replacement Using the XylE Gene as Selection Marker. 2016. Casanova, M., Pasotti L., Zucca S., Politi N., Massaiu I., Calvio C., Cusella De Angelis M.G., Magni P. Biological Procedures Online 18:6. DOI:10.1186/s12575-016-0036-z
• Metal Leaching and Reductive Dissolution of Iron from Contaminated Soil and Sediment Samples by Indigenous Bacteria and Bacillus Isolates. 2016. Styriakova I., Styriak I., Balestrazzi A., Calvio C., Fae M., Styriakova D. Soil & Sediment Contamination 25 (5), 519-535. DOI:10.1080/15320383.2016.1170102.
• γ-PGA Hydrolases of Phage Origin in Bacillus subtilis and Other Microbial Genomes. 2015. Mamberti S., Prati P., Cremaschi P., Seppi C., Morelli C.F., Galizzi A., Fabbi M., Calvio C. PLoS ONE 07/2015; 10(7):e0130810. DOI:10.1371/journal.pone.0130810.
• The Role of SwrA, DegU and PD3 in fla/che Expression in B. subtilis. 2013. Mordini S., Osera C., Marini S., Scavone F., Bellazzi R., Galizzi A., Calvio C. PLoS ONE 12/2013; 8(12):e85065. DOI:10.1371/journal.pone.0085065.
• pH-Dependent hydrolase, glutaminase, transpeptidase and autotranspeptidase activities of Bacillus subtilis γglutamyltransferase. 2013. Morelli C.F., Calvio C., Biagiotti M., Speranza G. FEBS Journal 11/2013; 281(1), 232-245. DOI:10.1111/febs.12591.
• Knockout of pgdS and ggt genes improves γ-PGA yield in B. subtilis. Scoffone V., Dondi D., Biino G., Pasini D., Galizzi A., Calvio C. Biotechnology and Bioengineering 07/2013; 110(7), 2006-2012. DOI:10.1002/bit.24846.
• Leaf-associated bacteria from transgenic white poplar producing resveratrol-like compounds: Isolation, molecular characterization, and evaluation of oxidative stress tolerance. 2009. Balestrazzi A., Bonadei M., Calvio C., Mattivi F., Carbonera D. Canadian Journal of Microbiology 07/2009; 55(7):829-40. DOI:10.1139/w09-038.
• SwrAA activates poly- -glutamate synthesis in addition to swarming in Bacillus subtilis. 2009. Osera C., Amati G., Calvio C., Galizzi A. Microbiology 05/2009; 155(Pt 7):2282-7. DOI:10.1099/mic.0.026435-0.
• Autoregulation of swrAA and Motility in Bacillus subtilis. 2008. Calvio C., Osera C., Amati G., Galizzi A. Journal of Bacteriology 07/2008; 190(16):5720-8. DOI:10.1128/JB.00455-08.
• Recovery of useful traits from isolates inhabiting an agricultural soil cultivated with herbicide-resistant poplars. 2008. Balestrazzi A., Bonadei M., Zelasco S., Quattrini E., Calvio C., Galizzi A., Carbonera D. Canadian Journal of Microbiology 04/2008; 54(3):201- 8. DOI:10.1139/w07-136.
• Swarming Differentiation and Swimming Motility in Bacillus subtilis Are Controlled by swrA, a Newly Identified Dicistronic Operon. 2005. Calvio C., Celandroni F., Ghelardi E., Amati G., Salvetti S., Ceciliani F., Galizzi A., Senesi S. Journal of Bacteriology 09/2005; 187(15):5356-66. DOI:10.1128/JB.187.15.5356-5366.2005.
Project Title:
The need of safer raw materials derived from renewable sources is driving an increasing interest towards natural biopolymers. γ-PGA is an anionic polymer produced by Bacilli, composed of thousands of glutamic acid units. Thanks to its non-toxicity, water solubility and biodegradability it finds application in several biotechnological fields as: flocculant for heavy metal removal, cryoprotectant, humectant, thickening additive in cosmetics and food industries, bioplastics, biological glue, drug or vaccine carrier or scaffold for biomedical engineering. However, for its full industrial exploitation it is mandatory to reduce production costs, both increasing bacterial productivity and reducing fermentation costs either increasing its yield or decreasing fermentation costs. Our Lab has obtained a producer strain derived from the fully characterized B. subtilis lab strain. The availability of a well-defined strain, which is genetically amendable, offers the opportunity to apply genetic engineering to improve productivity and rationalize metabolic pathways for lowering fermentation costs. By introducing specific mutations, we already obtained strains that show higher product yield. Currently our aim is to obtain a producer able to ferment organic components contained in some agro-industrial by-products. The meeting of the above objective will not only lead to cheaper γ-PGA but will also contribute to the valorisation of waste streams and reinforce the development of new bio-economy sectors.