The genome sequences of various kinds of prokaryotes and eukaryotes have completely been determined. Genome biology, which is going to systematically understand the whole system of living organisms at the molecular level, changed the image of traditional biology that focused on each local phenomenon one by one. The crucial question has raised how you understand a huge, complicated network having thousands of genes. "Systems Biology" is a promising methodology, but it has not been established.
How do you define a complete understanding of biological systems? As it is often invoked, the system of living cells can be compared with the case of a computer. Careful and extensive examination on the relationships between the input from a keyboard and the output to a screen never makes clear the internal structure and mechanism of the computer, although you know something of phenomenalism. How do you do to understand a computer system? An ordinary person disintegrates a computer into individual elements, and examines the relationships of the elements. Does it lead to complete understanding of the computers ? If so, you can reconstruct a computer using all the elements. Reconstruction could be defined as perfect understanding of systems.
This definition could be applied to a perfect understanding of a life. Advanced molecular biology attempts to explain a biological system at the level of molecule interactions. In the future, reconstructing a biological system at the molecular level may indicate a perfect understanding of life. Actually, the genes are being selected that are minimally necessary for cell activity. The day when a biological system is built based on the minimally required genes may come.
Our objectives are to develop the integrative technology, regarding information/systems/genetic engineering, that is necessary for synthesis and analysis of biological systems.
Computer simulation technology is required to rationally design a biological system composed of complicated gene regulatory networks with metabolic pathways.
In modern engineering, Computer-Aided Design (CAD) is extensively employed to build complex and huge artificial systems such as aircrafts and high tower building. Therefore, we develop the novel technology, called "Computer-Aided Design of Living SystEms (CADLIVE)". To achieve it, we explore the design principles underling molecular architectures, and establish novel technology of how to reconstruct a biological system based on the design principles.
1. Extraction of design principles of a biological system
- 1.1 Development of the simulator (CADLIVE) for gene regulation networks and metabolic circuits at the molecular interaction level
- 1.2 System analysis of biological networks for exploring the design principles based on control theory and information science.
2. Synthesis of a biological system
- 2.1 Reconstruction of metabolic systems with gene regulatory networks in silico
- 2.2 Development of novel rational technology of how gene regulatory networks are constructed at the molecular level.
3. Application to drug discovery and microbial engineering
- 3.1 Drug targeting for molecular networks based on network/pathway analysis
- 3.2 Computer-aided rational design of genetic microbes producing useful materials based on the design principles
Impact on Societies
This study not only contributes to life science in terms of a complete understanding of biological systems, but also gives great influence to advanced biotechnology. You can imagine that technology regarding rational design of living systems is directly tied to genetic improvement of microbes producing useful materials and discovery of drug targeting.
When microbes are cultivated in the environment suitable for growth, such as bioreactors, the genes that directly involve stress or survival responses may not be necessary. It will be very useful for bioindustry to genetically design the most suitable microbes for such artificial environment.
In addition to that, the integration of tremendous postgenomic information, which leads to discovery of new knowledge regarding the structure / function of molecular networks, contribute to development of novel medicine and advanced medical treatment.