| Career Summary |
1974: Graduated, Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo 1979: Ph.D. from University of Tokyo Research Associate, Institute of Medical Science, University of Tokyo Research Associate, Institute of Molecular Biology, University of Oregon Assistant Professor, Medical School, University of Tokyo Research member, National Children's Medical Research Center Associate Professor, Institute of Medical Science, University of Tokyo
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| Educational Activities |
Graduate school: System microbiology Undergraduate: Molecular Life Science II (Faculty of Science)
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| Research Activities |
One genome is a community of genes potentially with different interests. Their collaboration and conflicts underlie various aspects of genome dynamics, genome evolution and diseases. Our goal is to understand microbial genomes and their life and death from this point of view. A gene for a restriction enzyme, which cuts DNA at a specific sequence, is often linked with a gene for a cognate modification enzyme, which methylates the same sequence to protect it from cleavage. Restriction-modification (RM) gene complexes will attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, some RM systems sometimes behave as discrete units of life like viruses and transposons. Any threat to their maintenance, such as a challenge by a competing genetic element, can lead to cell death through restriction breakage in the genome. This post-segregational host cell killing or genetic addiction likely provides the RM complexes with a competitive advantage.

Restriction-modification systems
There is evidence that they move between genomes and rearrange them. They can even multiply.

Multiplying restriction-modification gene complex
Action of various machines of DNA recombination in the cells is understood well in terms of conflict with genetic elements within a genome. Earlier we proposed and demonstrated a double-strand break repair model for lambdoid bacteriophage-mediated recombination.
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Literature
1) M. Sadykov, Y. Asami, H. Niki, N. Handa, M. Itaya, M. Tanokura, I. Kobayashi, Multiplication of a restriction-modification gene complex. Mol. Microbiol., 48: 417-427 (2003). 2) N. Handa, Y. Nakayama, M. Sadykov and I. Kobayashi. Experimental genome evolution: large-scale genome rearrangements associated with resistance to replacement of a chromosomal restriction-modification gene complex. Mol. Microbiol., 40: 932-940 (2001). 3) A. Nobusato, I. Uchiyama, S, Ohashi, and I. Kobayashi. Insertion with long target duplication: A mechanism for restriction-modification-mediated gene mobility suggested from comparison of two complete bacterial genomes. Gene, 259: 99-108 (2000). 4) T. Naito, K. Kusano, I. Kobayashi. Selfish behavior of restriction-modification systems. Science, 267: 897-899 (1995). 5) A. Fujita, K. Sakagami, Y. Kanegae, I. Saito, I. Kobayashi. Gene targeting with a replication-defective adenovirus vector. J. Virol., 69: 6180-6190 (1995). 6) Y. Fujitani, K. Yamamoto, I. Kobayashi. Dependence of frequency of homologous recombination on the homology length. Genetics, 140: 797-809 (1995). 7) N. Takahashi, I. Kobayashi. Evidence for the double-strand break repair model of bacteriophage lambda recombination. Proc. Natl. Acad. Sci. USA, 87: 2790-2794 (1990).
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| Other Activities |
The Molecular Biology Society of Japan (MBSJ), The Genetics Society of Japan (GSJ), Society of Evolutionary Studies, Japan (SESJ)
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| Future Plan |
We wish to clarify molecular mechanisms of maintenance and evolution of genomes from the point of interaction of potentially selfish genes. We will analyze DNA double-strand breaks, their processing and their repair as programmed processes of genome death, maintenance and evolution. These analyses will contribute to understanding of microbes and their control.
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| Messages to Students |
Genome decoding opened a door to understanding life and death at the genome level. I hope you join us in this exciting phase of science.
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