SYSBIO Centre of Systems Biology
Description of Organization
In February 2008 the Italian MIUR (Ministry of Education, University and Research), made a call for proposals for the Italian Roadmap for ESFRI Research Infrastructures. Among the many hundred projects there was SysBioNet, a proposal made by the University of Milano-Bicocca on behalf of a group of scientists committed to develop studies of Systems Biology of complex cellular functions (from cell cycle to transformation). On December 2011 SysBioNet was selected as one of the few Research Infrastructures of the Italian ESFRI roadmap, funded with a 1.5 million euros for the fiscal year 2012. These contracts are generally three years long, renewable at least once.
SYSBIO, Centre of Systems Biology is the structure devoted to implement the SysBioNet project. SYSBIO has been formally created in june 2012 by a collaborative agreement of the National Research Council, with its two institutes (IBFM, Institute of Bioimaging and Molecular Physiology, Milan and IASI, Institute for Automation, Systems Theory and Informatics, Rome) and two departments of the University of Milano-Bicocca: Biotechnology and Biosciences and Information, System Science and Communication. Prof. Lilia Alberghina is the Director of SYSBIO.
SYSBIO is applying a molecular, multilevel approach to the investigation of complex cellular functions, from cell cycle to transformation, with a integration between biomolecular analysis and modeling/simulation studies. The distinctive features of SYSBIO research strategy considers each cellular function as given by the integration of discrete system-level properties. Each function is then analyzed by performing post-genomic analyses and tailor-made molecular/cellular investigations (notably, metabolic flux analysis (MFA) in case of properties that involve metabolism) of appropriately perturbed cellular systems with the aim to reconstruct the wiring of the molecular circuit that sustain the system-level property of interest, These studies allow to develop coarse-grain mathematical models to have a first idea of the dynamics of the process under investigation, able to constrain the following blow-up of relevant regulatory steps of the coarse-grain model. Given the consolidated expertise of SYSBIO in yeast systems biology, a line of work now active is aiming to use the budding yeast as a model to investigate the molecular controls of the shift to respiro/fermentative metabolism, that has many features in common with the Warburg effect in cancer cells. The idea is to use the genetic approach – much easier in yeast - to identify the control steps of the onset and maintainance of the metabolic shift observed in cancer cells.
Profile of staff members
A total of 27 staff members are enrolled in SysBio. Among them, Lilia Alberghina is an internationally renowned expert in cell cycle and systems biology, Cecilia Gelfi coordinates one of the Italian leading groups in proteomics, Giancarlo Mauri and Paola Bertolazzi coordinate groups active in development of ICT, bioinformatic and modelling tools and in their systems biology application, Danilo Porro leads a group leader in Europe in yeast biotechnology, Marco Vanoni has long time experience in computational and molecular analysis of signal transduction in eukaryotes. Several staff members are recipients of EU, MIUR (Italian Ministry for Research) and regional grants in the field of Systems Biology, cancer and neurodegeneration, ICT.
A web site is under construction
Five recent publications relevant to the project
1) AlberghinaL, GaglioD, GelfiC, MorescoRM, MauriG, BertolazziP, MessaC, GilardiMC, ChiaradonnaF, VanoniM. (2012) Cancer cell growth and survival as a system-level property sustained by enhanced glycolysis and mitochondrial metabolic remodeling Frontiers Physiol In the press
2) Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, Alberghina L, Stephanopoulos G, Chiaradonna F. (2011) Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol 7: 523.
3) Pescini D, Cazzaniga P, Besozzi D, Mauri G, Amigoni L, Colombo S, Martegani E. (2012) “Simulation of the Ras/cAMP/PKA pathway in budding yeast highlights the establishment of stable oscillatory states.” Biotechnology Advances 30: 99-107.
4) Palorini R, De Rasmo D, Gaviraghi M, Danna LS, Signorile A, Cirulli C, Chiaradonna F, Alberghina L, Papa S. (2012) Oncogenic K-ras expression is associated with derangement of the cAMP/PKA pathway and forskolin-reversible alterations of mitochondrial dynamics and respiration. Oncogene Mar 12. doi:10.1038/onc.2012.50.
5) Brümmer A, Salazar C, Zinzalla V, Alberghina L, Höfer T. (2010) Mathematical modelling of DNA replication reveals a trade-off between coherence of origin activation and robustness against rereplication. PLoS Comput Biol 6:e1000783.