|
Laboratory for Systems biology (LSB)
Systems biology as "biology after identification"
Recent large-scale efforts in genome-sequencing, expression profiling and functional screening have produced an embarrassment of riches for life science researchers and biological data can now be accessed in quantities that are orders of magnitude greater than were available even a few years ago. The growing need for interpretation of data sets, as well as the accelerating demand for their integration to a higher level understanding of life, has set the stage for the advent of systems biology, in which biological processes and phenomena are approached as complex and dynamic systems. Systems Biology is a natural extension of molecular biology, and can be defined as "biology after identification of key gene(s)." We see systems-biological research as a multi-stage process, beginning with the comprehensive identification and quantitative analysis of individual system components and their networked interactions, and leading to the ability to control existing systems toward the desired state and design new ones based on an understanding of structure and underlying principles (Fig. 0-1). The Laboratory for Systems Biology (LSB) at the RIKEN Center for Developmental Biology has specific aims to investigate development of systems-biological approaches and their application to system-level questions of complex and dynamic biological systems such as mammalian circadian clocks.
Figure 0-1. Systems Biology. Systems-biological research starts with comprehensive identification (upper left panel). In this step, individual system components and their networked interactions are comprehensively identified. In the second step, to derive the design principle of a target system, the behavior of the system is predicted and validated through an accurate measurement with perturbations (upper right panel). An understanding of the design principle of the system is essential to derive the method of controlling the system toward the desired state (lower left panel). Finally, the level of understanding is confirmed by reconstruction of the system (lower right panel).
Seamless Integration of Computation and Experiments
One of the characteristics of LSB is the seamless integration of computational and experimental technologies towards a higher-level understanding of biological systems. During the last five years, LSB has recruited researchers, technical staff, and students from a varied scientific and/or technological background, including molecular and cellular biology, genomics, biochemistry, bioimaging, bioinformatics, physics and applied mathematics and provided opportunities for its members to intensely interact with each other. LSB has also proved to be a good platform for researchers to carry out interdisciplinary collaboration, and in doing so incubate new concepts and technologies (Fig. 0-2). Interdisciplinary interaction is usually initiated spontaneously through a bottom-up manner in the LSB and has led a number of discoveries and inventions. The interdisciplinary atmosphere of the LSB also provides an excellent on-the-job training environment for students, technical staff, and researchers who intend to be multi-lingual researchers.
Figure 0-2. Interdisciplinary integrations in LSB. X axis shows technological classification (from wet to dry). Y axis shows classification of researchers by objects (from molecules to organisms). Each bar shows researcher's range of techniques. LSB members are able to cover a wide range of fields efficiently, all the while interacting with each other. This heterogeneity underlies the laboratory's ability to generate a "big-bang" in unexpected discoveries and inventions.
Perspective:
From Development of Approaches to System-level Questions
In attempting to accomplish the research aims outlined above, LSB has been mainly focusing on the development of a systems-biological approach during the last five years. We have successfully developed new strategies and technologies for genome-wide profiling, bioinformatics, quantitative measurement, perturbation of cellular state, and implementation of artificial circuits in cells (Fig. 0-3). We have also applied these systems-biological approaches to specific system-level questions, which has led to a number of new discoveries and inventions. Over the next five years, we plan on fully integrating these approaches in an attempt to realize a system-level understanding of the mammalian circadian clock. In order to facilitate these processes, we will also commit to the development of key technologies such as functional genomics used for complete identification of the mammalian circadian clock as well as Micro Electro Mechanical Systems (MEMS, also known as microfluidics) for quantitative perturbation of the mammalian circadian clock. These key technologies also have the potential to be applied to the study of developmental problems.
Figure 0-3. Perspective of LSB: From development of approaches to systems-level questions.
Strategies and technologies that invented in the last five years (left) are the building blocks for use in elucidating system-level questions over the next five years (right). Further development of functional genomics and introduction of MEMS technology will assist in the smooth changeover in research.
|
| Page Top |
