Research

SysBio is devoted to the study of complex biological functions (signaling, metabolism, cell cycle, cell death, neoplastic transformation, etc.), both in lower eukaryote and in mammalian cells.
Past results are listed below:

Yeast G1/S model

The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells. It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network . The authors report a mathematical model of the G1 to S network.

barberis2_opened

Text and pictures are taken from:
Barberis M, Klipp E, Vanoni M, Alberghina L (2007) Cell size at S phase initiation: An emergent property of the G1/S network. PLoS Comput Biol 3(4): e64. doi:10.1371/ journal.pcbi.0030064

Onset DNA Replication model

The large genomes in eukaryotic cells are copied from hundreds or thousands of replication origins to achieve the duplication of the entire DNA in a limited time span. Our computational analysis shows that optimized kinetic parameters are required for the biological functionality of the network, and such parameters indeed account for the measured kinetics of replication initiation.

brummer_DNA_initiation_replication_model

Text and pictures are taken from:
Brummer A, Salazar C, Zinzalla V, Alberghina L, Hofer T (2010) Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Replication. PLoS Comput Biol 6(5): e1000783. doi:10.1371/journal.pcbi.1000783

Yeast oscillatory regimes in the Ras/cAMP/PKA pathway

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Ras/cAMP/PKA pathway plays important role in the regulation of Saccharomyces cerevisiae (metabolism, cell cycle progression, stress resistance). The different controls mechanisms set the dynamics of this pathway and its players: we perform computational analysis to investigate this dynamical behaviors.

Find more information on this paper:
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. Biotechnol. Adv., 30, 1:99-107

Network analysis of cell Growth and Cycle

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The huge omics data are usually represented as a network of interacting components. This technologies doesn’t point out the cell control systems. A circuit analysis, an engineering approach, can be used to address the problem.

Find more information on this paper:
Palumbo, P, Mavelli, G, Farina, L, Alberghina, L (2010). Networks and circuits in cell regulation. Biochem. Biophys. Res. Commun., 396, 4:881-6

Cancer cell growth and metabolism

Oncogenes such as K-ras mediate cellular and metabolic transformation during tumorigenesis. A non-canonical labeling of TCA cycle-associated metabolites was detected in both transformed cell lines. Transcriptional profiling detected elevated expression of several genes associated with glycolysis, glutamine metabolism, and nucleotide biosynthesis upon transformation with oncogenic K-Ras.
These results provide evidence for a role of oncogenic K-Ras in the metabolic reprogramming of cancer cells.

gaglio

Find more information on this paper:
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.