Research outline
Cell growth and multiplication are a central problem in biology. Our proposal is focused on the adaptation strategy for cell cycle arrest by nutrient starvation and the re-initiation of growth when starved cells are returned to a rich medium. We want to investigate the molecular-switch problem: how cells can control and execute an arrest at the G0-like differentiated state, and how cell growth and division resumes when the nutritional environment improves. Understanding the transition from the G0-arrest to growing states at the molecular level is the purpose of this proposal.
We will employ post-genomic methods that produce quantitative information about individual genes in combination with genetic approaches using fission yeast as a model organism. If clear mechanistic principle emerges from these studies, we plan to extend the knowledge obtained to mammalian cell systems, using sets of conserved gene products. We aim to identify and characterize genes that command the G0-like cell stage or the return to growth. Our proposal has implications in broad research areas: cell cycle control, developmental biology, cancer research, chromosome biology, genome science and systems biology.
Research goals
- Understanding the molecular mechanism which regulates the switch between cell multiplication and quiescent state.
- Understanding the mechanism of maintanence of the G0 (quiescent) state.
What is G0?
G0 is a cell cycle stage, when cells cease division and remain in quiescent state.
As most cells of adult human body (brain, muscle, nerve...) are in G0 phase, it is important to understand how G0 phase is regulated.
Model organism
We use the fission yeast (Schizosaccharomyces pombe) as a model organism, all the ~4900 genes of which has been assigned from the whole genome.
| Human (Homo sapiens) |
Fission yeast (Schizosaccharomyces pombe) |
|---|---|
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|
~ 30,000 genes Genome size: 3 billion bp |
~ 4,900 genes Genome size: 14 million bp |
|
Strategy
- Comprehensive comparison of genes and proteins between G0 cells and dividing cells.
- Understanding the G0 regulation factors and G0 maintainance mechanism.
According to the result of the comprehensive analysis, candidates of G0 regulatory factors will be selected and be individually analyzed.
Expected outcome
Any essential progress in a basic "Cell growth and arrest" problem has certain impacton life science and will be welcome by human society. Control of cell growth has many application areas in medicine and biotechnology.
- Cancer therapy
- Suppressing abnormal cell multiplication
- Regeneration medicine
- Controlling cell multiplication
- Organ transplant
- Suppressing immune cells
References
- A nitrogen starvation-induced dormant G0 state in fission yeast: the establishment from uncommitted G1 state and its delay for return to proliferation. Su SS, Tanaka Y, Samejima I, Tanaka K, Yanagida M. J Cell Sci. 1996 Jun;109 (Pt 6):1347-57.
- Cnd2 has dual roles in mitotic condensation and interphase. Aono N, Sutani T, Tomonaga T, Mochida S, Yanagida M. Nature. 2002 May 9;417(6885):197-202.
- Regulation of checkpoint kinases through dynamic interaction with Crb2. Mochida S, Esashi F, Aono N, Tamai K, O'Connell MJ, Yanagida M. EMBO J. 2004 Jan 28;23(2):418-28
- Cleavage of Cohesin by Separase in Interphase Is Required for DNARepair. Nagao K, Adachi Y, Yanagida M. Nature. In press

