Current Research and Interest -1: Biology-related problems

1. Origin of Heredity (Information): Among many chemicals in a cell, only some specific chemicals (e.g., DNA) are regarded to carry genetic information. Why do only some specific molecules play the role of genetic information carrier? How were the roles of molecules separated into information carrier and metabolism? Is the separation a necessary consequence for a system to make recursive production of a cell with internal biochemical reaction dynamics? As a first step in investigating the origin of genetic information, we study how some species of molecules are preserved over cell generations and play an important role in controlling the growth of a cell. We have proposed a minority control theory for the origin of heredity. Ref.

   K. Kaneko and T. Yomo" On a kinetic origin of heredity :minority control in replicating molecules " J. Theor. Biol. 214 (2002) 563-576 (nlin.AO/0105031)

   K. Kaneko " Kinetic Origin of Heredity in a Replicating System with a Catalytic Network " J Biol. Phys., in press

   
   
2. Universal Feature of a Cell with Recursive Growth Questions: A cell consists of several replicating molecule species that, through mutual interaction, help the synthesis of new molecules and maintain some synchronization for replication. The very least, a membrane that partly separates a cell from the outside has to be synthesized, and this process must keep some degree of synchronization with the replication of other internal chemicals. How can such recursive production and chemical diversity be maintained at the same time? Is there some universal feature in these reaction dynamics? Furthermore, this recursive production is not exact and slow `mutational' changes appear over the generations in an evolutionary process. How is this evolvability possible in the presence of recursive production? We found Zipf's law in the abundance of chemicals for a reproducing cell, which is also confirmed in real data in a cell, as Zipf's law in gene expressions. Next, we have studied fluctuations of abudnances of each chemical, to show ubiquity of the log-nromal distribution. This is also confirmed by experiments. investigated.

   C. Furusawa and K. Kaneko " Zipf's law in Gene Expression " Phys. Rev. Lett., 90 (2003) 088102 (pdf file )
   

   C. Furusawa, T. Suzuki, A. Kashiwagi, T. Yomo and K. Kaneko; submitted (2003)

   
   
   
3. General Theory for Fluctuations and Stability of a Cell Relationship between fluctuation and response in a biological system is proposed by extending the fluctuation-disspiation theorem in physics. This proposition is applied to evolution experiments. We are also discussing relatoinship between genotypic and phenotypic fluctuations.

   K. Sato et al., PNAS 2003

   
   
   
4. Theory for Cell differentiation Questions: How do identical cells diversify into discrete types through development and how can these distinct cell types be maintained by recursive production? How are the characteristics of each cell type stabilized in the presence of molecular fluctuations, and how can the number distribution of cell types stably be maintained? We proposed isologous diversifictaion theory, based on the study of coupled dynamical systems. (Ref)

   K. Kaneko and T. Yomo, ``Isologous Diversification: A Theory of Cell Differentiation ", Bull.Math.Biol. 59 (1997) 139-196;

   K. Kaneko and T. Yomo, ``Isologous Diversification for Robust Development of Cell Society", J. Theor. Biol.,

   
   
   
5. Context-dependent rule for cell differntiation from a stem cell Questions: In the development of multi cellular organisms, so-called stem cells that either proliferate or differentiate into other cell types play an essential role. What are the rules for differentiation from multipotent stem cells and how are these differentiation rules generated? How can such rules and several cell types coexist stably under fluctuations? Using chaotic intracellular dynamics, we showed that a rule for hierarachical differentiations gnerally emerges, and proposed `chaotic stem cell hypothesis'. We have made several predictions on the characteristics for differentiations from stem cells, some of which are experimentally confirmed. ref:

   C. Furusawa and K. Kaneko"Theory of Robustness of Irreversible Differentiation in a Stem Cell System: Chaos Hypothesis" J. Theor. Biol. (2001) 209 (2001) 395-416

   C. Furusawa and K. Kaneko ``Emergence of Rules in Cell Society: Differentiation, Hierarchy, and Stability", Bull.Math.Biol. 60 (1998) 659-687

   
   
   
6. Stability and Irreversibility in the Development of Cell Societies Questions: In the development of multi-cellular organisms, there is a successive determination from totipotent ES cell, to multipotent stem cells, and finally to several determined cell types. A clear temporal direction in the loss of potency for forming a variety of cell types exists in the normal course of development. How is such irreversibility generated and how is it characterized quantitatively? Is such irreversibility related to developmental stability? ref.

   Kunihiko Kaneko and Chikara Furusawa ``Robust and Irreversible Development in Cell Society as a General Consequence of Intra-Inter Dynamics", Physica A 280 (2000) 23-33 (also available at http://arXiv.org/abs/chao-dyn/9912005)

   
   
   
7. Pattern Formation and the Origin of Positional Information Question: Biological pattern formation (morphogenesis) is understood as a change of genetic expression that depends on the spatial gradient of chemicals. This gradient supposedly provides information on the position of each cell. The positional information then leads to a change in the concentration of the signal molecules, and thus finally to a change of the genetic expressions. Still the question remains: How is such positional information generated? In order to form gradients, spatial differentiation of cells is necessary. Extending the theory for cell differentiation, generation of positional information is demonstrated, which turns out to be robust against external pertubations.

   C. Furusawa and K. Kaneko ``Generation of Positional Information ..", to be submitted to J Tneo. Biol.

   C. Furusawa and K. Kaneko ``Origin of complexity in multicellular organisms", Phys. Rev. Lett. i84 (2000) 6130-6133

   C. Furusawa and K. Kaneko" Complex Orgnization in multicullarity as a necessity in evolution" Artificial Life, 6(2000) 265-281

   
   
   
8. Origin of Multicellular Organisms Questions: In order for a multicellular organism to exist over successive generations, the cell aggregates themselves have to be replicated recursively (i.e., recursiveness at the cell ensemble level is a necessity). How is this recursive replication at the ensemble level achieved? Furthermore, the offspring of a multicellular organism usually does not begin its life by inheriting all the cell types of the mother (parents) but by the fertilization of a single specific cell type, called germ cell. Why does the development of multicellular organisms have to pass through such narrow bottleneck? Is this related to the mechanism of recursive generation?

   C. Furusawa and K. Kaneko " Origin of Multicellular Organisms as an Inevitable Consequence of Dynamical Systems " Anatomical Record, in press

   
   
   
9. Evolution; in particular in relatiohship with development and phenotypic plasticity Questions: Darwin asked why organisms are separated into distinct groups, rather than their character being continuously distributed. If two organisms, due to minor genetic changes, differ only slightly in phenotype, then they share a common niche and compete for survival. Consequently, it is difficult for two groups with only slight genetic differences to coexist. Then how is sympatric speciation possible when organisms live in the same space interacting each other? We showed that ionteraction-induced phenotype plasticty leads to genetic diversification. In particular, when phenotype separate into two groups, genetic separation into the two groups follows, leading to sympatric speciation. Hybrud sterility is resulted, and the premating isolation also follows as a result of postmating isoloation.

   K. Kaneko and T. Yomo "Genetic Diversification through Interaction-driven Phenotype Differentiation" Evol Eco. Res., 4 (2002) 317-350

   K. Kaneko " Symbiotic Sympatric Speciation: Compliance with Interaction-driven Phenotype Differentiation from a Single Genotype " Population Ecology, 44 (2002) 71-85

   K. Kaneko and T. Yomo ``Sympatric Speciation: compliance with phenotype diversification from a single genotype" Proc. Roy. Soc. B, 267 (2000) 2367-2373

   
   
   
10. Evolution of Genetic System: How has genetic system evolved to make correspondence with genotype and phenotype? In relationship, we are interested in the evolution of genetic code.

    H. Takagi, K. Kaneko, and T. Yomo ``Evolution of genetic code through isologous diversification of cellular states", Artificial Life, 6(2000) 283-305

    
    
    
11. Symbiosis Questions: Individual biological units sometimes join to form a new unit. For example, endosymbiosis is believed to have played an essential role in the origin of the eucaryotic cell. Such joining of systems must generally be difficult. For example, consider two independent logical systems, say two separately written, independent computer programs. Then it would be almost impossible for a mere composite system of the two to work without error. On the other hand, in biological systems such joining seems to have occurred sometimes during the course of evolution, as, for example, is discussed in the endosymbiosis theory. Then, how can two independent biological systems (with independent biochemical networks) join to form a new composite system without damaging (killing) each system?
    
    
12. Dynamic Memory and Learning The emergence of memory is ubiquitous in biological systems and not limited to neural networks. Cells generally are able to store the history of the external influences that they have experienced in their internal state up to some extent. In order to form a memory, external changes that occur at relatively fast time scales have to be transformed into internal changes that have much longer time scales. Changes of the internal state at such longer time scales may alter later responses of the internal state against further external stimuli. This alteration can be regarded as learning. Hence the question is: under what conditions can external stimuli at faster time scales be transformed into long-term changes of the internal state? In other words, under what conditions can a system have memory and learn?
    
    
13. Energy Transduction in Interacting Molecules, in partial relationship with Molecular Motor

    N. Nakagawa and K. Kaneko " A dynamic mechanism of energy conversion to a mechanical work " Phys. Rev. E; also in Phyisca A

    
    
    
14. Consturction of `Complex Systems Theory' for Biological System in general ( so far mostly in relationship with development and cell differentiation)

    K. Kaneko, ``Organization through Intra-Inter Dynamics", to appear in ``Organizations" (MIT press) eds. G. Mueller and S. Newmann

    K Kaneko ``From Coupled Dynamical Systems to Biological Irreversibility", Adv in Chem Phys. (2002)

    
    
    

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