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


Sensing and amplifying weak signals are critical for life things to adapt to the severe environment. These sensing and signal transduction systems have been highly developed to play the role in the course of evolution. For example, we can raise immune and neurotransmission systems. These systems work very effectively, however application usages of those are limited because they only work in living cells. Sensing and signal transduction systems made of purified biomolecules and/or chemicals will overcome the situation.<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>


&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>


Signal transduction with defined biomolecules and chemicals needs two system; sensing systems to external signals and transmit systems to amplify the signals. Liposomes have high responsibility to environment and have been used to release molecules out from the inside. DNA is beneficial for specific-action and transmission, because of its high selective-specificity and flexibility. If above system is made of DNA and liposomes, we can realize the nano-scaled flexible amplifier. Thus, we aim at creating molecular-releasing systems using DNA and liposomes.<br
<!--
Is it possible to create similar one to the biological signal transduction system? If it is possible, we can design more effective molecular amplification. We can expect new applications. For instance, the molecular amplification can be used in a smart drug delivery system. Such mechanism may also allow us to artificially develop our nerve system.
-->


<h3>Project: Lipo-HANABI</h3>
<h3>Project: Lipo-HANABI</h3>
As our summer project, we decided to construt a signal amplification system by using Liposomes and DNA nanotechnology.
&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>
 
The system has two stages: "Initiation by senseing environment" and "Amplification of signals by chain-reactive burst of liposomes".
 
<!--
 
Our project goal is to design molecular-releasing systems that amplify and transmit small signals. Here, Lipo means liposome, in which we store the payload molecules, and Hanabi is fireworks in Japanese.
<br>
<br><br>
-->
 
<h4>First stage : Initiation by senseing environment</h4>
The first stage senses environmental changes, and release secondary signals into the amplifier in the sexcond stage. In this project, we chose temperature as an environmental initiator because of controllability. Increasing temperature induces disruption of initial liposomes. Key DNA inside the liposomes is released and transmit signals into the second-stage amplifier<br>
 
 
<h4>Second stage: Amplification by chain-reactive burst of liposomes</br>
The second stage recieve the signals from the first stage, and then amplify them by a chain reactive liposome destruction. The liposomes in the second stage encapsulate key DNAs and payload moleclules (like drugs). Once a liposome is disrupted, neighbor liposomes are also disrputed by the key DNA. This happens continuously, and then, the number of disrupted liposomes increases exponentially. Since the second-stage liposome also encapsulate payload molecules as a response to signals, the response initiated by the first signals is amplified in this stage.<br><br>
 
The advantage of the two-stage strategy is that we can make various types of signal amplification system without changing the 2nd stage. <br><br>


This system works like a HANABI (Japanese fireworks), because HANABI is resulted from chain-reactive bursts initiated by fire (first signal). Thus, we termed the project as "Lipo-HANABI" (we should note Lipo means liposomes).<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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<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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