The University of Tokyo · 생화학·유전·분자생물학
Chikara Furusawa 교수의 연구실은 생물세포 내 대사 및 유전자 발현의 정량적 동역학을 수리모델링을 통해 탐구하는 데 초점을 맞추고 있습니다. 단순한 반응망 모델을 통해 세포의 자가복제 효율성과 관련된 '지프의 법칙'과 '로그노멀 분포' 같은 보편적 통계 법칙이 어떻게 유도되는지를 규명하며, 생명체의 조직화 원리에 대한 근본적인 통찰을 제공합니다. 특히 유전자 변동, 단백질 농도 변동, 세포 성장 동역학 등에서 나타나는 내재적 소음과 비선형 동역학의 상호작용이 세포 기능과 다형성에 어떻게 기여하는지 연구하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Using data from gene expression databases on various organisms and tissues, including yeast, nematodes, human normal and cancer tissues, and embryonic stem cells, we found that the abundances of expressed genes exhibit a power-law distribution with an exponent close to -1; i.e., they obey Zipf's law. Furthermore, by simulations of a simple model with an intracellular reaction network, we found that Zipf's law of chemical abundance is a universal feature of cells where such a network optimizes th
The discovery of two fundamental laws concerning cellular dynamics with recursive growth is reported. Firstly, the chemical abundances measured over many cells were found to obey a log-normal distribution and secondly, the relationship between the average and standard deviation of the abundances was found to be linear. The ubiquity of these laws was explored both theoretically and experimentally. By means of a model with a catalytic reaction network, the laws were shown to exist near a critical
We quantified the growth behaviour of all available single-gene deletion and overexpression strains of budding yeast. Genome-wide analyses enabled the extraction of the genes and identification of the functional categories for which genetic perturbation caused the change of growth behaviour. Statistical analyses revealed defective growth for 646 deletion and 1302 overexpression strains. We classified these deleted and overexpressed genes into known functional categories, and identified several f
The genome-scale metabolic model provides useful information for the evaluation of the metabolic capabilities and prediction of the metabolic characteristics of C. glutamicum. This can form a basis for the in silico design of C. glutamicum metabolic networks for improved bioproduction of desirable metabolites.
How can a microorganism adapt to a variety of environmental conditions despite the existence of a limited number of signal transduction mechanisms? We show that for any growing cells whose gene expression fluctuate stochastically, the adaptive cellular state is inevitably selected by noise, even without a specific signal transduction network for it. In general, changes in protein concentration in a cell are given by its synthesis minus dilution and degradation, both of which are proportional to
The origin of multicellular organisms is studied by considering a cell system that satisfies minimal conditions, that is, a system of interacting cells with intracellular biochemical dynamics, and potentiality in reproduction. Three basic features in multicellular organisms-cellular diversification, robust developmental process, and emergence of germ-line cells-are found to be general properties of such a system. Irrespective of the details of the model, such features appear when there are compl
A reduction in high-dimensional phenotypic states to a few degrees of freedom is essential to understand biological systems. Here, we show evolutionary robustness causes such reduction which restricts possible phenotypic changes in response to a variety of environmental conditions. First, global protein expression changes in Escherichia coli after various environmental perturbations were shown to be proportional across components, across different types of environmental conditions. To examine if
A simple cell model consisting of a catalytic reaction network is studied to show that cellular states are self-organized in a critical state for achieving optimal growth; we consider the catalytic network dynamics over a wide range of environmental conditions, through the spontaneous regulation of nutrient transport into the cell. Furthermore, we find that the adaptability of cellular growth to reach a critical state depends only on the extent of environmental changes, while all chemical specie
Recovery of pluripotency from determined cells is a long-standing aspiration, from both scientific and clinical perspectives. Our hypothesis suggests a feasible route to recover the potential to differentiate, i.e., by increasing the variety of expressed genes to restore chaotic expression dynamics, as is consistent with the recent generation of induced pluripotent stem (iPS) cells.
The origin of multicellular organisms and the mechanism of development in cell societies are studied by choosing a model with intracellular biochemical dynamics allowing for oscillations, cell-cell interaction through diffusive chemicals on a two-dimensional grid, and state-dependent cell adhesion. Cells differentiate due to a dynamical instability, as described by our "isologous diversification" theory. A fixed spatial pattern of differentiated cells emerges, where spatial information is sustai
Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a "cooperative" use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave "selfishly." The releva