Biomod/2013/Todai/Project: Difference between revisions
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Revision as of 23:22, 30 August 2013
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<img src="http://openwetware.org/images/9/9c/Logo-OCKver.png" width=730px height=128px>
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</figure>
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<br>
<div class="sidebar">
<ul>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai">Home</a>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Project">Project</a>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Design">Design</a>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Result">Result</a>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Experiment">Experiment</a>
<ul style="list-style-type: none;">
<li>
<a href="http://openwetware.org/wiki/Biomod/2013/Todai/Experiment#Contents">
Contents</a></li>
<li>
<a href="http://openwetware.org/wiki/Biomod/2013/Todai/Experiment#PilotStudy">
Pilot Study</a></li>
<li>
<a href="http://openwetware.org/wiki/Biomod/2013/Todai/Experiment#Protocols">
Protocols</a></li>
</ul>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Team">Team</a>
</li>
<li><a href="http://openwetware.org/wiki/Biomod/2013/Todai/Sponsors">Sponsors</a>
</li>
</ul>
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<html> <head> <title>Project-Todai nanORFEVRE-</title> <style>
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<ul>
<li><a href="#Background and problem">Background&Problem</a>
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<li><a href="#Solution">Solution</a>
</li>
<li><a href="#Project Goals">Project Goals</a>
</li>
</ul>
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<!--Project-->
<h1 class="big-title"><a name="Project"> Project</a></h1> <br>
<!--BGP-->
<article> <h1 class="title"><a name="Background and problem"> Background and problem</a></h1> <br>
<!--paragraph1-->
<article>
<figure class="figure-left">
<img style="float:left; margin:0;margin-right:-10px;margin-bottom:10px;"
src="http://openwetware.org/images/e/e8/Bgp4-1-Todai.png" width="350px" height="272px" >
</figure>
<br>
<br>
<p class="paragraph">
Cancer is one of the most malignant diseases. In cancer, cells get abnormal, divide and grow uncontrollably, forming malignant tumors, and invade human body. It accounts for about 13 percent of deaths in the world.
</p>
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src="http://openwetware.org/images/d/d8/Bgp4-2-Todai.png" width="350px" height="272px" >
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<p class="paragraph">
One of the most effective medical treatments for cancer is chemotherapy, but it often has severe side effects. This is because anti-cancer drugs attack not only cancer cells but also normal cells, damaging normal tissue and organs. According to <a href="http://www.cancer.org/" style="color:#e00000;">the American cancer society</a>, these side effects include pain, vomiting, limphedemia, sexual decline and various symptoms, which seriously decrease quality of life.
</p>
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<article>
<figure class="figure-left">
<img style="float:left; margin-right:-10px; margin-left:0px;"
src="http://openwetware.org/images/d/d0/Bgp4-3-Todai.png" width="350px" height="272px" >
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<p class="paragraph">
To improve cancer-specificity, drug delivery system has also developed recently, but it is difficult to customize a delivery system one by one corresponding to each drug.
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<article>
<p class="paragraph" style="font-size:130%">
Team Todai nanORFEVRE are trying to make <span style="font-weight:bolder;color:#e00000;">cancer-specific drug which doesn’t need delivery system</span>.
</p>
<br>
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<img style="margin-top:0px;"
src="http://openwetware.org/images/b/bf/Bgp4-4-Todai.png" width=450px height=350px >
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</article>
<br>
</article> <br> <br>
<!--Solution-->
<article> <h1 class="title"><a name="Solution"> Solution</a></h1> <br>
<!--paragraph1-->
<article>
<figure class="figure-left" style="position:relative;left:-40px;">
<img style="float:left; margin-right:-20px; margin-left:0px;"
src="http://openwetware.org/images/7/7f/Solution3-1-Todai.png" width="330px" height="257px" >
</figure>
<p class="paragraph" style="font-size:105%;">
To realize a cancer-cell-killing system with high specificity, we first focused on a mechanism in the human immune system called membrane attack complex (MAC), which functions when bacteria infect our body. In the system of MAC, subunits penetrate the membrane, oligomerize, and form a pore through the bacteria membrane. Then the subunits disrupt the lipid bilayer and lead the targeted cells to lysis and die. Subunits show citotoxity only after forming a pore. They don’t kill the cell simply by penetrating it. Molecules on the surface of harmless cells prevent MAC from sticking in (and forming pores), so MAC will only show citotoxity to foreign cells such as bacteria.
</p>
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</article>
<!--paragraph2-->
<article>
<p class="paragraph">
We decided to kill the (cancer) cells. But the natural cancer-recognition is far more complicated than referred above, in which a lot of molecules are related. So we had to device artificial approach for the cancer-recognition system. Actually, there is a research that tries to develop pore-forming proteins like MAC <span class="ref-sup"><a href="#proref-1">[1]</a></span>,but in that research they could not reach the point of discrimination.
</p>
<figure>
<center>
<img src="http://openwetware.org/images/2/2f/Solution3-2-Todai.png" width=450px height=350px >
</center>
</figure>
</article>
<br>
<!--paragraph3-->
<article>
<p class="paragraph">
Then, we thought about using DNA for recognition system. In situ computation by DNA was reported in <i>Nature Nanotechnology</i>(Maria Rudchenko et al.(2013)).
<span class="ref-sup"><a href="#proref-2">[2]</a></span>
DNA was used as logic circuits which uses surface antigens as inputs and generates DNA strands as outputs. They said it may be possible to use this logic circuit for other self assembling systems and DNA machinery. By using DNA, we thought we can make cancer-recognition system.
</p>
<br>
<br>
</article>
<!--paragraph4-->
<article>
<p class="paragraph">
Therefore, our general idea is explained as follows. Subunits stick in normal and cancer cells nonspecifically. Then only when cancer-specific antigens are expressed, DNA computing circuit puts out certain DNA strand. And this strand triggers oligomerization of the subunits and citotoxity is induced. To control oligomerization by DNA strand, we think several mechanisms. For example, using output strand in the toehold system
<span class="ref-sup"><a href="#proref-3">[3]</a></span>
that triggers hyblidization of subunits. Overall, subunits oligomerize only on the cancer cells and kill only cancer cells. We believe that our Oligomeric Cell Killer has the potential to treat cancer and other diseases like infection, and as the basis of DNA origami robotic system in which multiple molecules coordinate according to logic computation performed by DNA itself.
</p>
<br>
<figure>
<center>
<img src="http://openwetware.org/images/5/57/Solution3-3-Todai.png" width=450px height=350px >
</center>
</figure>
</article>
<br>
</article> <br> <br>
<!--ProjectGoals-->
<article> <h1 class="title"><a name="Project Goals"> Project Goals</a></h1>
<!--paragraph1-->
<article>
<p class="paragraph">
Our general idea can be divided into two steps, <span style="color:#e00000">cancer-recognition</span> and <span style="color:#e00000;">killing</span>. DNA computing circuit for recognition was developed in the past research<span class="ref-sup"><a href="#proref-2">[2]</a></span>, so we set the goal of the biomod 2013 <span style="font-weight:bolder;color:#e00000;">the development of pore-forming DNA origami for the killing system</span>. To achieve this goal, we thought about biomolecular robotic system named as Oligomeric Cell Killer explained in
<a target="_blank" href="http://openwetware.org/wiki/Biomod/2013/Todai/Design"
style="color:#e00000">
the Design page
</a>.
</p>
<br>
</article> <br>
<!--paragraph2-->
<article>
<p class="paragraph">
We can divide the project goal <b>"the development of pore-forming DNA origami for the killing system"</b> into following five steps.
</p>
<br>
<ul class="project-list">
<li>DNA strands assemble to form designed structures.</li>
<li>The formed subunits oligomerize in the solution.</li>
<li>Subunits stick in the membrane.</li>
<li>Subunits oligomerize on the membrane.</li>
<li>Subunits form the pore and kill the cell.</li>
</ul>
<figure>
<center>
<img src="http://openwetware.org/images/8/8c/Projectgoals-new2-Todai.png" width="700px" height="500px" style="position:relative;left:-22px;" >
</center>
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</article>
<br>
<!--paragraph3-->
<article>
<p class="paragraph" style="font-size:110%;">
<span style="color:#e00000">However</span>,
our project remains still very complicated and before actually using Oligomeric Cell Killer in the experiments, we should know what conditions should be set. So we also designed
<a target="_blank"
href="http://openwetware.org/wiki/Biomod/2013/Todai/Design#CylinderinBarrel">
<span style="color:#e00000">Cylinder in barrel by DNA origami as the simple model of Oligomeric Cell Killer</span></a>,
and perform experiments referred above with it <span style="color:#e00000">first</span>.
</p>
</article> <br>
<!--paragraph4-->
<article>
<p class="paragraph" style="font-size:110%;">
We showed what we did in each step in
<a target="_blank" href="http://openwetware.org/wiki/Biomod/2013/Todai/Result"
style="color:#e00000">
the Result page
</a>.
</p>
</article>
<br>
<br>
<!--References-->
<article>
<h1 class="title"><a name="References"> References</a></h1>
<br>
<div>
<div class="reference-title">
<a name="proref-1">
[1] Rational combinatorial design of pore-forming β-sheet peptides
</a>
</div>
<div class="reference-author">
Joshua M. Rausch, Jessica R. Marks, and William C. Wimley
</div>
<div class="reference-journal">
PNAS 2005 102 (30) 10511-10515; published ahead of print July 14, 2005, doi:10.1073/pnas.0502013102
</div>
</div>
<br>
<div>
<div class="reference-title">
<a name="proref-2">
[2] Autonomous molecular cascades for evaluation of cell surfaces
</a>
</div>
<div class="reference-author">
Maria Rudchenko, Steven Taylor, Payal Pallavi, Alesia Dechkovskaia, Safana Khan, Vincent P. Butler Jr, Sergei Rudchenko & Milan N. Stojanovic
</div>
<div class="reference-journal">
Nature Nanotechnology 8, 580–586 (2013) doi:10.1038/nnano.2013.142
</div>
</div>
<br>
<div>
<div class="reference-title">
<a name="proref-3">
[3] Transcription Regulation System Mediated by Mechanical Operation of a DNA Nanostructure
</a>
</div>
<div class="reference-author">
Masayuki Endo, Ryoji Miyazaki, Tomoko Emura, Kumi Hidaka, and Hiroshi Sugiyama
</div>
<div class="reference-journal">
Journal of the American Chemical Society 2012 134 (6), 2852-2855
</div>
</div>
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</article> <br> <br> <br> <br> <br> <br> <br> <br>
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