Cinzia Calvio
Cinzia Calvio
affiliation: Università di Pavia
research area(s): Molecular Biology, Genetics And Genomics
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 got the degree in Applied Genetics from the Specialization School in “Genetica Applicata” at the University of Pavia. From Sept. ’92 till Dec. 95 she held a Postdoc position at the EMBL, Heidelberg, in the laboratory of Prof. A.I. Lamond. A second Postdoc was carried out at the European Institute of Oncology - IEO, Milan, in the group led by Prof. P.G. Pelicci. In June 1997 she held a Product specialist position at BIOSENSE srl, a commercial company based in Milan. In 1999 she obtained a Research assistant position and, in 2003, became Assistant Professor in Genetics, at the Dept. of Genetics and Microbiology of the University of Pavia, in the lab of Genetics of Microorganisms. Since then her main research interest has been the regulation of stationary phase phenotypes in the model organisms Bacillus subtilis. In particular she characterized the swrA dicistronic operon necessary for swarming, a specialized form of motility. Recently she identified the complex regulation driving the expression of swrA. These studies have demonstrated the existence of another phenotype not described before in domestic strains of B. subtilis: the production of an anionic polymer of great industrial interest, poly gamma-glutamate (PGA).
In Bacillus subtilis she characterized the swrA dicistronic operon necessary for swarming, a specialized form of motility exhibited on solid surfaces. More recently she identified the complex regulation driving the expression of the swarming gene swrA and demonstrated the existence of a positive autoregulatory loop established by SwrA and the transcription factor SigmaD. She also found out that in the stationary phase swrA is expressed only in the presence of the phosphorylated form of DegU. DegS/U are members of bacterial two component systems. In B. subtilis DegS/U responds to an unknown signalling pathway activated by changes in the medium osmolarity. These studies have demonstrated the existence of another phenotype which had never been described before in domestic strains of B. subtilis: the production of an anionic polymer of great industrial interest, poly-gamma-glutamate (PGA). PGA production in B. subtilis is due to the joint presence of SwrA and the phosphorylated form of DegU. The nature of the interaction between SwrA and DegU is the key point to explain several stationary phase phenomena in B. subtilis.
Cinzia Calvio’s activities are currently funded by a PRIN project, by the Regione Lombardia-INSTM consortium and by the ALMA MATER Foundation.
1. OSERA C, AMATI G, CALVIO C., GALIZZI A. SwrAA activates poly-gamma-glutamate synthesis in addition to swarming in Bacillus subtilis.
MICROBIOLOGY, vol. 155; p. 2282-2287, 2009.
2. CALVIO C., OSERA C, AMATI G, GALIZZI A. (2008). Autoregulation of swrAA and motility in Bacillus subtilis.
JOURNAL OF BACTERIOLOGY, vol. 190; p. 5720-5728, 2008.
3. BALESTRAZZI A., BONADEI M., CALVIO C., GALIZZI A., CARBONERA D. DNA extraction from soil: comparison of different methods using spore-forming bacteria and the swrAA gene as indicators.
ANNALS OF MICROBIOLOGY, vol. 59; p. 827-832, 2009.
4. BALESTRAZZI A, BONADEI M, CALVIO C., MATTIVI F, CARBONERA D. Leaf-associated bacteria from transgenic white poplar (Populus alba L.) producing resveratrol-like compounds: isolation, molecular characterization and oxidative stress tolerance.
CANADIAN JOURNAL OF MICROBIOLOGY, vol. 55; p. 829-840, 2009.
5. BALESTRAZZI A., BONADEI M., ZELASCO S., QUATTRINI E., CALVIO C., GALIZZI A., CARBONERA D. Recovery of useful traits from isolates inhabiting an agricultural soil cultivated with herbicide-resistant poplars.
CANADIAN JOURNAL OF MICROBIOLOGY, vol. 54; p. 201-208, 2008
6. CALVIO C., CELANDRONI F, GHELARDI E, AMATI G, SALVETTI S, CECILIANI F, GALIZZI A, SENESI S. Swarming differentiation and swimming motility in Bacillus subtilis are controlled by swrA, a newly identified dicistronic operon.
JOURNAL OF BACTERIOLOGY, vol. 187; p. 5356-5366, 2005.
Project Title:
Improving biosynthesis of Gamma-PGA in domestic strains of B. subtilis
The increasing concern for industrial processes based on safe raw materials obtained by renewable sources prompts the widespread interest towards natural biopolymers. Poly-gamma-glutamic acid (PGA) is a natural polyanionic polymer formed by thousands glutamate residues linked by amide bonds. Thanks to its absolute non-toxicity, water-solubility, biodegradability it finds potential applications as flocculant absorber of heavy metals in wastewater treatments, cryoprotectant and humectant, thickener, food and feed additive, biological adhesive, vaccine and drug carrier and as scaffold biomaterial in biomedical applications. PGA is produced by wild bacterial isolates mainly belonging to the genus Bacillus. However, for industrial applications, it is necessary to reduce the currently high production costs by enhancing bacterial productivity and improving the fermentation conditions.
Recently, a new Bacillus subtilis producer strain has been derived from the fully characterised laboratory strain 168 (Osera, Amati, Calvio, Galizzi, 2009). Microbiology, 155:2282-2287). The availability of a well studied laboratory strain allowed our group to exploit genetic strategies for strain improvement and to rationalize the culturing conditions, overcoming the heuristic approach thus far applied with wild producers. By introducing selected mutations interfering with several metabolic pathways we aim to obtain strains displaying an improved and sustained accumulation of PGA, as recent results are confirming. This project, particularly the characterization and chemical derivatization of purified PGA, is carried out in collaboration with organic and drug chemists at Universities of Pavia & Milan, and is funded by two different grants.

Project Title:
Elucidating the mode of action of SwrA, a regulatory protein of unknown function
Two-Component Systems(TCS) are composed of a sensor histidine kinase and a response regulator, generally a transcription factor, that regulates gene expression. The sensor protein is autophosphorylated upon signal perception and transmits the stimulus to its cognate response regulator by phosphorylation. The phosphorylation status of the regulator modifies its transcriptional properties and thus gene expression. In B. subtilis the two component system DegS-DegU is a central regulator, controlling the expression of more than 100 genes that characterize the transition from the exponential to the stationary growth phase and coordinates single cells fates in multicellular communities. DegS-DegU are activated upon hyperosmotic stress, although the biochemical nature of the signal perceived by DegS remains elusive.
Both swarming and PGA production are regulated by the phosphorylation state of DegU and by the action of SwrA, a protein of unknown function and without any similarity with previously characterized proteins. Evidences accumulated in our lab in the last few years suggest that SwrA has a role, in fact, in the modulation of DegU transcriptional activity.
In the lab, most of the molecular tools necessary for the dissection of the molecular mechanisms of DegU activation are already available (recombinant proteins, mutant strains, biological assays). By using several techniques, ranging from molecular biology to biochemistry and microscopy, we aim to address: i) the mechanism of action of SwrA; ii) the regulation of the phosphorylation state of DegU; iii) the pathways leading to DegS-DegU TCS activation.
This project is currently funded by a PRIN grant.