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Design and Control of Cellular Functions

Research Supervisor:
Hiroki Ueda
(RIKEN Center for Developmental Biology)

Outline of research area

In this area of research, we seek to gain insights into the principles of living systems through the design and control of cellular functions. Toward this end, we will seek to establish new concepts and technologies with broad applications. In particular, this research will address, but not be limited to, the following areas:
1) Logical (or efficient) design and control of biomolecules involved in cellular functions
2) Reconstitution and design of processes that support the infrastructure of cellular function (e.g., genomes, metabolic networks, cell-free translation systems, cell membrane division)
3) Reconstitution, design, and control of processes that implement higher-order cellular functions (e.g., signal transduction, gene network, intercellular communication)
4) Reconstitution, design, and control of populations of cells, tissues, organs, and individual organisms.
5) Construction of a framework for the implementation of open innovation toward the design and control of cellular function unifying diverse fields, such as chemistry, physics, information science, engineering and life science

This field of study covers not only creative basic research projects based in unique concepts, but more ambitious applied researches, which may advance medicine and solve energy problems, as well.

Research Supervisor's Policy for Recruitment, Selection, and Administration

In its quest to answer the question "What is life?" the life sciences have been advancing rapidly with the discovery of various biomolecules and through analysis of their functions. More than 10 years have passed since decoding of a series of important genomes, including that of the human, around the year 2000. As a result of this catalogue of genetic information (the genome) becoming available, developments based on the analysis of individual biological phenomena have accelerated our understanding of the blueprints of the cell, the fundamental unit of life. Among these developments, in vitro reactions of biomolecules have already aided in the successful reconstruction of intracellular phenomena such as replication, transcription, and translation. This type of constructive approach is in its infancy, but even before now, diverse and deep expertise has been acquired on how biomolecules generate cellular functions. Through testing, reconstitution, design and control of cellular functions, opportunities to gain further insight into the design principle of cells have increased both in Japan and overseas. Accordingly, the purpose of this field of study is to establish new trends in the life sciences that may help to advance our understanding of life and provide broad applications through a broad-ranging constructive approach, from molecule design to the composition of non-human embryos. A constructive (or synthetic) approach encompasses a qualitative understanding of molecular networks and defining sufficient conditions for molecular networks to function. This also differs from the descriptive (or analytical) approach, which emphasizes data collection, in taking an alternative approach that places greater importance on the quantitative predication and verification of the dynamic behavior of biological systems, which also has the benefit of driving forward a cycle of theoretical and experimental development. Furthermore, a constructive approach requires the formularization and quantification of various phenomena, and, through performing experimental verification of theoretical prediction, makes clear the discrepancies between the targeted biological functions and current knowledge and theory. Such discrepancies give rise to new areas for further research, and serve to prompt deep questioning and understanding of the target phenomena, and ultimately we hope, full control over them. Recently, a larger theme involving the unification of this kind of constitutive approach, namely, "reconstruction and design of cell", has come to be actively discussed both in Japan and overseas. These discussions enforce a constant awareness of the research problem at hand, namely, how do we know whether "cells" are created? It also leads to continuous and active discussion about the fundamental questions in life science, such as "What is a cell?" and "What is life?" For that reason, a constructive approach takes not only a natural science perspective, but also takes into account social and cultural involvement. The size of DNA sequences that can be synthesized is increasing exponentially. To date, the DNA sequence of gene size and virus size have been fully synthesized, and last year in 2010, synthesis of the bacillus genome was accomplished. If the development of DNA synthesis continues at this pace, it may become possible to synthesize genomes the size of the human genome by 2015-2020. What kind of developments in life science will be possible at that point? It is hoped that the birth of "synthetic" life science can be witnessed through participation in this field of study. In this research area, the following two criteria (either one or both) on the part of candidate research proposals have been selected for emphasis: 1) an interest in trying to address scientific questions through the design and control of biological systems; and 2) the importance of basic techniques (and frameworks) for attempting to implement and promote the design and control of biological systems. We welcome original individual research proposals satisfying either criterion, as well as proposals from not only researchers in life science, but also those in physics, chemistry, engineering, information science, and social science. In the case that multiple fields of expertise are needed to realize the research objectives, we welcome PRESTO research projects that aim to link with researchers from other fields than the applicant's. (Please specify the expertise and roles of the applicant and the party/parties with whom the applicant seeks to have links). We received a record number of research proposal applications during FY2011. We have accepted a wide variety of proposals, including those with the following three subject areas:
(1) understanding interesting biological phenomena with a constructive approach,
(2) development of techniques and methods for the design and control of cellular functions, and
(3) development of techniques and methods for the foundation of synthetic biology and regulatory biology.
Since a record number of applications were received, we could not accept many good proposals. Please refer to the following points if you plan to re-apply using the submitted projects or with new projects:
1. We are looking for research proposals that extend beyond the mere "description" or "identification" of factors in biological phenomena. We strongly recommend that applicants consider their research plans from a more constructive perspective, according to their experience.
2. If the project theme is related to innovative and advanced technology development, please describe in detail "what" the new technology facilitates and "how" it leads to a better understanding of biological phenomena and cellular functions.
3. Research proposals and plans would be more persuasive if they contain preliminary data, supporting your working hypothesis, or the readiness of the experimental techniques.
4. Major areas that are expected to develop in the future are synthetic and regulatory biology of biological phenomena at organism levels, or life science research which is initiated from theory and information.
However, we were unable to accept sufficient number of proposals in these areas during the last fiscal year. We recommend that you consider the submission of any future proposals that fall under these areas.

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