About Our Research
The organelles inside the cell look to be conserved among all eukaryotes. Is the intracellular design, like size, shape of organelles and their positions inside the cell, also conserved? To look for these universal design principles of the intracellular design, our laboratory tackles the mechanisms for controlling the organelles design especially focusing on the design of the cell nucleus which all eukaryotes have. Understanding the universal design principles and their mechanisms of which eukaryotes have made choices during a long history, we would like to consider ultimately how eukaryotes having nuclei have been evolved.
The cell nucleus conserved among all eukaryotes can change in size depending on the environments inside and outside the cell. The most basic rule of nuclear size is a size relationship between the nucleus and the cell, which has long been observed for more than 100 years. So, the nucleus can sense the size information of the cell and control its own size.
An important question is how the nucleus can sense the cell size. We are trying to unravel the general rules and underlying mechanisms by utilizing a cell-free system for recapitulating intracellular structures and manipulating some cellular spatial parameters in vitro.
Using the cell-free system, we have found that
the mechanism that the local space surrounding the nucleus controls the nuclear growth speed [Hara & Merten, 2015]
the mechanism that some intracellular structures impede the nuclear growth [Shimogama et al, 2022]
the difference in mechanisms for nuclear size control between two frog species [Heijo et al, 2022]
We would like to try to analyze the size scaling mechanisms for other organelles and how multiple organelles coordinate their sizes.
Mission 2: Does the Nucleus Know the Interior Status of the Nucleus?
The cell nucleus has DNA by wrapping the membrane. The amount and structure of the DNA are dynamically changed during the cell cycle and during development. Surprisingly, the nucleus has mechanisms for controlling its size by sensing the physical status of DNA. This feature has also long been observed for more than 40 years.
In addition to the scaling with cell size, we are trying to address how the nucleus can sense the DNA status within the nucleus and control its size by utilizing the cell-free system.
Using the cell-free system combined with the manipulation techniques of DNA amount and structures, we have demonstrated experimentally how DNA amount and structures affect nuclear size. However, it is still in the enigma of physical mechanisms and molecular basis of how DNA expands the nucleus from the inside. We are tackling these remaining questions in the future.
Mission 3: Is There a Golden Ratio of the Nuclear Size?
全ての真核生物がもつ核のサイズは、生物種や細胞の種類により大きく異なります。そのサイズ調節の仕組みには、何か特別な法則性があるのでしょうか？真核生物の進化の過程で、その法則性はどのように変化したのでしょうか？細胞がもつ「黄金比率」のような、特別な核サイズはあるのでしょうか？
私たちは、上記Missionの仕組みの実験的な理解に加えて、生物種間の核サイズの比較解析も行っています。これまでに、800種類以上の細胞のデータを集めて核サイズを比較したところ、
・特定の真核生物では、核サイズがもつ法則性が他の真核生物・原核生物とは異なること
・真核生物の有核赤血球では、核サイズがもつ法則性が他の一般的な体細胞とは異なること
を解明してきました。[詳しくはこちら！(現在準備中)]
このような進化的観点の解析から、原核生物から真核生物への進化や、真核生物種内での進化の過程で、遺伝情報を保有する核（や核様体）の特徴や機能がどのように変化して生きたのかを理解したいと思っています。いづれは、核の構造や機能を人工的に進化・改良するような実験にもトライしたいです。
Mission 4: その他のオルガネラのサイズスケーリング!?
核以外の様々なオルガネラのサイズや機能も、細胞のサイズや環境に合わせて変化しています。私たちは、上記のアプローチを駆使して、核以外のオルガネラのサイズスケーリングの仕組みとその生物学的意義に関しても、解析を進めていきたいと思っています。また、オルガネラ間のサイズスケーリングの関係も含めて、細胞全体のスケーリングの関係を理解できるようになると面白いですね。
