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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>

 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> 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> 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>

 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>  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">

 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> 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> The released key molecules attach on the Second stage liposomes and induce puncture of them.

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

 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> 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> 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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@@ Line 38: / Line 38: @@
              <a href="http://openwetware.org/wiki/Biomod/2013/Sendai/sponsor" class="whiteSendai">Sponsor</a>
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-              <a href="http://openwetware.org/wiki/Biomod/2013/Sendai"><h1 style="color:white;" ><b>Biomod<span>2013<br>&emsp; Team</span>Sendai</b></h1></a>
+              <a href="http://openwetware.org/wiki/Biomod/2013/Sendai"><h1 style="color:white;" ><b>Biomod<span>2013<br>&emsp;Team</span>Sendai</b></h1></a>
      </header>
+  <div id="ttop">
+<a href="#top" class="page_top" onfocus="this.blur();" onclick="scrollTo(0,0); return false;" title="Top"></a></div>
    <section role="main">
          <article>
 <h2>Project</h2>
-<h3>Background</h3>
+<Img Src="http://openwetware.org/images/1/16/Top%E7%B5%B5-ver2final_mini.jpg"><br>
-生物は厳しい自然界で生き残るために重要で微小なシグナルを増幅し、伝達するシグナル伝達を進化させてきた。…ry
-In the course of evolution, living organisms have evolved various mechanisms for transmitting and amplifying small signals to survive in the harsh environment.  Such mechanisms of signal transduction and amplification are crucially important for the maintenance of life, and we have many examples of mechanisms in sensing systems, immune systems and neurotransmission systems.<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>
-<img src="http://openwetware.org/images/9/97/Sendai-pro-fig1-01.jpg"><br>
+<h3>Motivation</h3>
-図１　生物の微小なシグナルに対する反応の例(ヒトは自然界の微小なシグナルを検知してそれを体内に伝達し、それに対処する反応ができる)<br>
-Fig. 1 The example of reaction to tiny signal of life(Human sense tiny signal in the natural world and transport to inside of the body and can take action to the signal.)
-<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>
-現代のヒトが感知できない微小なシグナルを、生物のシグナル伝達と人間のデザインを組み合わせることで感知できるようにならないだろうか？そうすればいろいろな応用が考えられる。例えばヒトが気づかないままに進行する病気を感知したり、危険の神経伝達をより早く感知したりすることができる。<br>
-Is it possible to sense undetectable stimulate by combining organic signal transduction and artificial design. If it is possible, we can design very effective molecular amplification mechanisms for various applications such as sensing unnoticed developing disease or dangerous situation.
-<img src="http://openwetware.org/images/4/4d/Sendai-pro-fig2-01.jpg"><br>
-図２　感知できなかったものが感知できるようになる世界(体内でヒトの無自覚に進行する血管の炎症を無自覚のうちに人工的な分子放出システムが治療する。こ)<br>
-Fig. 2 The world that can sense something which can't be sensed.(Artificial molecular releasing system cure the unconsciously advancing inflammation in a blood vessel.)
-<br>
-<h3>Project Goal </h3>
+<h3>Project: Lipo-HANABI</h3>
-微小なシグナルを増幅する分子放出システムには微小なシグナルに反応できる小さなものから反応が始まりその反応が指数関数的に増幅していくシステムが必要である。<br>
+&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>
-Amplifying molecular system needs a mechanism starts with small reaction and amplifies it.
-そのためには以下の条件を満たすことが必要である。<br>
+<h4>First stage: Sensing system</h4>
-（１）様々な微小な刺激（入力）に対し、様々な分子放出（出力）ができること。<br>
+<Img Src="http://openwetware.org/images/1/1d/%3Basfinal.jpg" width="45%" height="45%" style="padding-left:10mm" align="right">
-そのためには、内部に様々な分子を入れられる小さな容器と、その蓋をあける様々なしくみ（放出のメカニズム）を用意できることが必要になる。<br>
-（２）特定の外的刺激だけに対応して放出が起こること。<br>
-　放出のためのシグナルとしては、いろいろなものが考えられる。<br>
-　光、ｐH、特定の化学物質の濃度、電磁場・・・・<br>
-　これらの変化に対してのみ反応することできる容器が必要である。<br>
-この（１）（２）の条件を満たす「容器」として私たちはリポソームを使用した。理由はリポソームの中には様々な分子を入れることができ、リポソーム表面にリポソームを破壊するための様々な分子を修飾することができるから、またそのことにより温度感受性・光感受性・pH感受性リポソームという特定の外的刺激にのみ反応するリポソームがすでに考えだされている※からである。<br>
-※ref<br>
-（３）分子の放出が連鎖すること。<br>
-反応が何度も続いて反応を増幅するために、リポソームのふたが開いたときに中に入っていた分子で他のリポソームの破壊がおこるようにして反応が連鎖するようにする。そのためにはリポソームのふたを開けることができ、かつ選択性のある分子をリポソームに閉じ込めておく必要がある。<br>
-この（３）の条件を満たすために私たちはDNAをリポソームに閉じ込め、DNAで次々にリポソームを割ろうと考えた。なぜなら、DNAの配列をデザインすることで特異性・選択性を持たせることができるからだ。<br>
-しかし、いまだかつてDNAでリポソームを割るという試みはなかった。ここがわたしたちのプロジェクトにとって重要で大きな障壁である。<br>
-（４）放出される分子の量、および放出のタイミングが適切にコントロールできること。<br>
-刺激に対して、分子放出の関係がきちんと予測可能であることが必要である。それぞれが微弱であっても、ノイズでないレベルの信号が来た時には放出がおこらなければならない。<br>
-つまり、入力出力比（増幅率）がある程度なければならない。<br>
-この（４）の条件を満たすかどうかを私たちはシミュレーションにより確かめた・<br>
-To construct the molecular releasing system sensing tiny signal, following things are needed.<br>
-(1) To execute various kind of output from various kind of output from various kind of stimulus(entry) <br>
-To solve this problem, we have to make cases to confine various  kind of molecules and arrange mechanisms to open the case (mechanism to release) <br>
-(2) To operate release reaction in response to only a specific external stimulus<br>
-As signals to release, there are various factors like light, pH, concentration of chemical agent, electro-charged field. <br>
-To operate release reactions, we have to make cases to react to only these changes. <br>
-(3)To build relationship to release molecular<br>
-If one tiny stimulus opens one case, it is no use causing the reaction singly.　Considering this factor, we have to make a mechanism to build relationships between the cases and moleculaes in the case and to amplify the reaction, keeping behavior continue time after time. To resolve above problems, we have to design molecular that can opens the top of the case. <br>
-(4)To control the amount of molecular and when the cases will release the molecules.
-When the system senses stimulus, it have to control the amount of molecules and when the case will release the molecules. Even though these stimulus and releasing amount are tiny, this system have to release molecules except noises. <br>
-In other words, a certain gain,level of the proportion of input and output is needed. <br>
-→confer simulation <br><br>
-こうして外部刺激とその中のDNAやPayload（反応の連鎖には関与しないが薬など特定の箇所で役に立つもの）の組み合わせにより様々な放出系のデザインが可能であるが、今回のプロジェクトではその基本的な例として温度上昇を感知して反応の開始となるDNAを放出しそれが周囲の反応を連鎖させるDNAをもつリポソームが割れていく系の構築を目指すことにした。<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.
-この系は一点から周囲へとリポソームの破壊が連鎖的に広がっていく系であるため、その様子が日本のHANABI（Firework）に似ていることから私たちはこの系をLipo-HANABIと呼ぶことにした。<br>
-<br>
-To meet above conditions (1) and (2), we used liposome. There are two reasons to select. It can confine various molecular and can be conjugated by various molecular. ( correspond to (1)).There are many liposome sensing one specific external stimulus like temperature-sensitive one, light sensitive one and pH sensitive one. ( correspond to (2)) <br>
-*ref<br>
-To meet the (3) condition, we designed the system that DNA release molecules. We selected DNA because it has specificity and optionality by designing it. <br>
-However, anyone haven’t tried to collapse by DNA. This point is the most important and the hardest barrier for us. <br>
-Finally, to demonstrate validity, we ran a simulation <br>
-Establish a link here (by Off-san) <br>
-From above things, various releasing system can be created. Among various system, this project aims at the system releasing DNA from liposome when temperature rises and DNA collapse other ones containing DNA. <br>
+<h4>Second stage: Amplification system</h4>
-In this system, the collapse of liposome prevails chain-reactively and looks like Japanese HANABI (fireworks). So we call this system Lipo-HNANBI. <br>
-<img src="http://openwetware.org/images/5/5b/Sendai-pro-fig3-01.jpg"><br>
+<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">
-図３　微小な反応を感知してそれを感知できる大きさに増幅する分子放出システムに必要な要素<br>
-Fig. 3 The needed factor for the molecular releasing system sensing tiny reaction and amplifying to the sensitive size<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
+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>
-</p>
          </article>

Biomod/2013/Sendai/project: Difference between revisions

Latest revision as of 23:07, 26 October 2013

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