Laboratories

Laboratory of Bioinformatics and Systems Biology (Department of Biological Sciences, Graduate School of Science) Recruiting students for the academic year 2018

Professor Shinya Kuroda
Department of Biological Sciences, Graduate School of Science(Hongo)
+81-3-5841-4697
E-mail: skuroda{at}bs.s.u-tokyo.ac.jp
Lab HP
field of study:Systems Biology

Systems biology of cellular signaling

【Key Words】Systems biology, trans-omics, metabolism, diabetes

 Our research is aimed to the understanding of the features of signaling pathways and examining them as a type of “channel”for communication to the extracellular environment. In particular,we first proposed the concept of“temporal information coding,”which embed information to the time pattern of molecular activation. Since information processing is performed through the molecular interactions too complex to understand with conventional methods we therefore create models that replicate the behavior of signaling pathway by the cooperation and feedback between simulation models and the actual measurements of cell behavior (Fig. 1).

Fig.1 Strategy of System Biology

Information coding of signaling pathways

1.Insulin action

 Insulin is the only hormone that lowers blood sugar levels. Blood insulin concentration varies in temporal patterns and the physiological significance of this has been reported in the past, while the molecular mechanism is poorly understood. From the view point of“temporal information coding,”it is possible that information is encoded in these time patterns, and target organs responses are individually controlled in a time-dependent manner. Our research has hown that the information encoded in the insulin time pattern is multiplexed in the AKT time pattern,allowing downstream molecules to be individually controlled (Fig.2). In the future we hope to perform animal experiments to give an in vivo demonstration of temporal information coding and to uncover the mechanism behind it. We also hope to improve our understanding of insulin’s actions by combining various layers of comprehensive measurement technologies to automatically detect signal pathways that straddle multiple hierarchies.

2.Mechanisms of cell fate determination

 Signal transduction networks including ERK elicit multiple cellular functions. One of the critical properties of the signal transduction system is that the same signaling net-works can code multiple cellular functions. We have recently found that the distinct temporal coding of ERK signaling networks regulate cell growth and differentiation in PC12 cells in response to EGF and NGF. We are currently trying to explore the decoding mechanism of distinct temporal patterns of ERK activation via downstream molecular networks.

Fig.2 Temporal coding of insulin action

3.Trans-omics of insullin action

 We explored signal flows of insulin,an important hormone for metabolic homeostasis. We reconstructed the static signal flow of insulin based on time-series phosphoproteome and metabolome data together with multiple databases and found where an insulin signal flowed through a global transomic network. We analysed the dynamic signal flow using kinetic modelling together with model selection and model reduction, and found when specific phosphorylation and allosteric regulation selectively control temporal patterns of metabolites. Thus, we demonstrate a global landscape for the signal flow of insulin, which reveals the large-scale mechanism of metabolic homeostasis.
 Sytems biology requires fundamental knowledge from a wide variety of fields, including the life sciences, physics, information science,and mathematics. We therefore do our best to maintain a multidisciplinary research staff with highly diverse backgrounds.


Fig.3 The large-scale trans-omic networks

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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