Ultimate goal of our study is systems understanding of mechanisms of signal transduction networks which regulate various cellular functions including cell-fate determination, synaptic plasticity and hormonal actions. Both experimental methods as well as computer simulations are needed for the systems understanding. Thus, we are trying to understand cellular functions by use of the computer simulations together with experimental methods. The final step of our study is to extract simple and essential rules by model reduction of the detailed simulation model. The extracted simple and essential rules turn out to be general principle of cellular functions. Current ongoing projects are listed below.

1.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 networks can code multiple cellular functions. This coding system can be generated by the combination of distinct signaling molecules/networks and by distinct temporal coding systems. 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 (Nat. Cell Biol., 7, 365-373, 2005). We are currently trying to explore the decoding mechanism of distinct temporal patterns of ERK activation via downstream molecular networks. In addition, the cross talk between ERK and PI3 kinase has recently been shown to regulate cell-fate determination, which we are also starting to work on. These coding mechanisms can be one of the general principles of signaling networks.

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2.Synaptic plasticity

Synaptic plasticity is believed to be the cellular basis for learning and memory. Synaptic strength can be modified in a bi-directional manner, depending on the relative timing of pre- and postsynaptic spiking. This spike timing-dependent synaptic plasticity (STDP) is thought to play an important role in neural development and information storage. A full understanding of the mechanism and function of STDP requires synergistic integration of experimentation and computation. We have currently developed the electrophysiological and biochemical models of STDP. Using this model, we preliminarily predicted the novel kinetics of NMDA receptors, which has been under validation by experiments. This will provide us a novel biologically plausible synaptic learning rule, which was firstly postulated by Hebb.

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3.Information coding of signaling networks

On the basis of our finding in ERK signaling networks, we are currently trying to find novel coding mechanisms of signaling networks. We will upload when we will have substantial results.

Because we try to train students and post-doc to be bilingual in both wet experiment and dry computer simulation, we welcome anyone with various background as well as nationalities and genders who is interested in systems biology. If you want to know our projects, job opportunities etc in detail, please email to skuroda@is.s.u-tokyo.ac.jp.

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