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        <h2>Project</h2>
<h2>Project</h2>
<h3>Background</h3>
<Img Src="http://openwetware.org/images/1/16/Top%E7%B5%B5-ver2final_mini.jpg"><br>


DNAナノテクノロジーの将来的な目標として、物質の輸送・放出を行うシステムの構築がある。ナノスケールでの輸送、放出システムは汎用性が高く非常に魅力的である。例えば薬品を放出するようにすれば直接細胞に作用するようなDDSが可能となる。また放出という点に着目すれば、神経に代表されるようなシグナル伝達システムの実現もできるだろう。
<h3>Background</h3>
このようなシステムの構築に向けて、輸送系、制御系、放出系などについて様々な基盤研究がおこなわれている。
<br>


<img src="http://openwetware.org/images/d/de/Project-fig1-00.jpg" width="400" height="400"><br>
&nbsp;For all living organisms, sensing weak signals in environment and amplifying them are critically important to survive. Various types of signal sensing/ transduction systems have been highly developed in the course of evolution, e.g. immune and neuro-transmission systems.<br>&nbsp;These systems are not only astonishingly sensitive but very effective and efficient. If we could borrow principles from the living systems, we could create a system with novel functionalities.<br>&nbsp;In our project, we decided to create a sensing and signal transduction systems made of designed artificial biomolecules and chemicals.<br><br>


<h3>Motivation</h3>
<h3>Motivation</h3>
効果的な分子放出システムを作るのに、放出する分子の量を制御することは重要である。
また狭い範囲に選択的に分子の放出ができればそのシステムの価値は格段に向上する。
量と場所の制御は効果的な放出システムの構築には欠かせないものである。
もし、反応の始まりのシグナルを限られた場所に放出でき、そのシグナルをもとに分子の継続的な放出が可能ならばこの2つの大切なポイントが果たされるのではないか?
これが私たちのプロジェクトのモチベーションである。
<br>


Controlling the quantity of molecular release is very important to develop effective release system. <br>
&nbsp;In order to realize a signal transduction system, we need to develop two types of system; a sensing system that detects external signal and a transmitting system that amplifies the signal and releases large amount of output molecules (payloard). We adopt liposomes as a container of the system. <br><br>
Delivering drugs molecular at appropriate places which are usually very narrow spaces is another important point to avoid adverse effect. <br>
If initial releasing signals are released at a very limited place, and if the signals continuously transduce the initial signals with releasing molecular, are the two important points fulfilled?
This is the motivation of our project.<br>
<br>


<h3>Project Goal</h3>
私たちのプロジェクトは連鎖反応的分子放出システム(チェーンリアクティブバースト)の構築を目指している。<br>
Our project aims to construct a chain-reactive molecule-releasing system in a spontaneous manner like organisms.<br>
If chain-reactive collapse of liposomes happens in a limited space, release of drugs inside liposomes is expected to be controlled around a limited space. Our chain-reactive burst system is a good one for doing this strategy.<br>


Each liposome encapsulates trigger DNAs and ペイロード, and has aptamer DNAs in their outer surface.ペイロードとはある個所で必要とされる物質のことで、例えば薬や化学的なシグナルとなる物質が挙げられる。 <br>
<h3>Project: Lipo-HANABI</h3>
&nbsp;In our system, stored molecules in liposome are released in chain-reaction triggered by environmental stimuli. The system adopts a two-stage mechanism as follows.<br><br>


Hybridizations of trigger DNAs and aptamer DNAs deform liposome rapidly, and consequently, the liposomes are destroyed. This destruction continuously occurs by releasing new trigger DNAs inside liposomes to disrupt neighbor liposomes. These processes achieve concentrated drug release. We call these processes as “Chain-reactive burst.” <br>
<h4>First stage: Sensing system</h4>
<br>
<Img Src="http://openwetware.org/images/1/1d/%3Basfinal.jpg" width="45%" height="45%" style="padding-left:10mm" align="right">


しかし、HANABIが自然発生的にあちこちで起こるとペイロードが必要でない場所に放出されてしまう可能性がある。<br>
&nbsp;The First stage detects a certain signal in the environment, and release molecules to activate the Second stage. In this project, we chose temperature change as an environmental signal that initiates the whole process.<br>&nbsp;Namely, we use a temperature-sensitive liposome for the First stage. At a certain triggering temperature, they break and release key molecules for the Second stage. <br>&nbsp;The released key molecules attach on the Second stage liposomes and induce puncture of them.
そのため、このチェーンリアクティブバーストをペイロードが必要な場所で開始させるために、特定の条件を感知した後に反応(チェーンリアクティブバースト)が開始するようにした。具体的には特定の条件を感知できるリポソームを作製し、それが反応の一番初めのトリガーDNAを放出するようにした。<br>
特定の条件の例としては温度やpH、光などがあるが、今回は「温度上昇」を反応開始の条件として設定した。<br><br>


<img src="http://openwetware.org/images/2/20/Project-chain.png" width-"400" height="600">
<h4>Second stage: Amplification system</h4>


<h3>Methods</h3>
<Img Src="http://openwetware.org/images/e/e9/Top%E7%B5%B5-final_mini.jpg" width="45%" height="45%" style="padding-left:10mm" align="right">
To develop the egg-type initiator, following experiments are needed. We plan to create the egg-type initiator by combining these sub-parts.<br>
 
<br>
&nbsp;The Second stage liposomes contain both the payload molecules (e.g. drug) and the same key molecules released by First stage. Once some of them break, it releases more key molecules, and they break other liposomes in their neighborhood. <br>&nbsp;As a consequence, bursting of the liposomes propagates exponentially in a chain-reactive way and releases a lot of payload molecules
シグナルを感知するシステムを備えたチェーンリアクティブバーストを実現するために以下の実験が必要である。
The advantage of adopting the two-stage strategy is that various types of signal in the environment can be detected by First stage design, without changing the Second stage.<br>&nbsp;The mechanism of this system is similar to that of HANABI (fireworks in Japanese), therefore, we termed the project "Lipo-HANABI".<br>
(1) トリガーDNAとリポソームを破壊するアプタマーDNAの設計と構築
(2) 周辺のリポソームの破壊によって放出された新しいトリガーによりリポソームの破壊の連鎖が起こることの確認
(3) 温度上昇を感知して割れるリポソームの機能確認
To develop the chain-reactive burst, following experiments are needed. <br>
(1) Design and construction of trigger DNA and aptamer DNA to cause collapse of liposomes.<br>
(2) Confirm chain reaction of liposomal collapse by new triggers inside disrupt neighbor liposomes.<br>
(3) Collapse of liposomes by temperature shift<br>


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<h2>Project</h2> <Img Src="http://openwetware.org/images/1/16/Top%E7%B5%B5-ver2final_mini.jpg"><br>

<h3>Background</h3>

&nbsp;For all living organisms, sensing weak signals in environment and amplifying them are critically important to survive. Various types of signal sensing/ transduction systems have been highly developed in the course of evolution, e.g. immune and neuro-transmission systems.<br>&nbsp;These systems are not only astonishingly sensitive but very effective and efficient. If we could borrow principles from the living systems, we could create a system with novel functionalities.<br>&nbsp;In our project, we decided to create a sensing and signal transduction systems made of designed artificial biomolecules and chemicals.<br><br>

<h3>Motivation</h3>

&nbsp;In order to realize a signal transduction system, we need to develop two types of system; a sensing system that detects external signal and a transmitting system that amplifies the signal and releases large amount of output molecules (payloard). We adopt liposomes as a container of the system. <br><br>


<h3>Project: Lipo-HANABI</h3> &nbsp;In our system, stored molecules in liposome are released in chain-reaction triggered by environmental stimuli. The system adopts a two-stage mechanism as follows.<br><br>

<h4>First stage: Sensing system</h4> <Img Src="http://openwetware.org/images/1/1d/%3Basfinal.jpg" width="45%" height="45%" style="padding-left:10mm" align="right">

&nbsp;The First stage detects a certain signal in the environment, and release molecules to activate the Second stage. In this project, we chose temperature change as an environmental signal that initiates the whole process.<br>&nbsp;Namely, we use a temperature-sensitive liposome for the First stage. At a certain triggering temperature, they break and release key molecules for the Second stage. <br>&nbsp;The released key molecules attach on the Second stage liposomes and induce puncture of them.

<h4>Second stage: Amplification system</h4>

<Img Src="http://openwetware.org/images/e/e9/Top%E7%B5%B5-final_mini.jpg" width="45%" height="45%" style="padding-left:10mm" align="right">

&nbsp;The Second stage liposomes contain both the payload molecules (e.g. drug) and the same key molecules released by First stage. Once some of them break, it releases more key molecules, and they break other liposomes in their neighborhood. <br>&nbsp;As a consequence, bursting of the liposomes propagates exponentially in a chain-reactive way and releases a lot of payload molecules The advantage of adopting the two-stage strategy is that various types of signal in the environment can be detected by First stage design, without changing the Second stage.<br>&nbsp;The mechanism of this system is similar to that of HANABI (fireworks in Japanese), therefore, we termed the project "Lipo-HANABI".<br>


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