Biomod/2013/Todai/project

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   <br>

 <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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<div class="rightbar-pro">

 <ul>
    <li><a href="#Background and problem">Background&amp;Problem</a>
    </li>
    <li><a href="#Solution">Solution</a>
    </li>
    <li><a href="#Project Goals">Project Goals</a>
    </li>
 </ul>

</div>

  <h1 class="big-title"><a name="Project">&nbsp;Project</a></h1>
  <br>

  <article>
   <h1 class="title"><a name="Background and problem">&nbsp;Background and problem</a></h1>
   <br>

 <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 common diseases in the world. Cancer cells divide abnormally and grow uncontrollably, resulting in the formation of malignant tumors, and invading human body. Cancer causes about 13 percent of the all human deaths worldwide (WHO 2007).

      </p>
      <br>
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 </article>

    <article>

       <figure class="figure-right">
         <img style="float:right;margin:0;margin-left:-10px;" 
         src="http://openwetware.org/images/d/d8/Bgp4-2-Todai.png" width="350px" height="272px" >
       </figure>

      <p class="paragraph">

Chemotherapy is a popular medical treatments for the cancer, however, it often attacks normal cells in addition to the cancer cells, damaging normal tissue and organs, which cause severe side effects. According to <a target="_blank" 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>
      <br>     
      <br>
      <br>
      <br>
  </article>

    <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" >
      </figure>
      <br>
      <br>
      <br>

      <p class="paragraph">
      To improve cancer-specificity, drug delivery system (DDS) has developed, but it is difficult to optimize a delivery system for each drug.
      </p>
      <br>
      <br>
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    </article>

    <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 (DDS)</span>.
      </p>
      <br>

      <figure>
        <center>
          <img style="margin-top:0px;"
          src="http://openwetware.org/images/f/f2/Todai_project_back4.4.png" width=450px height=350px >
        </center>
      </figure>
    </article>
    <br>

  </article>
  <br>
  <br>

  <article>
   <h1 class="title"><a name="Solution">&nbsp;Solution</a></h1>
   <br>

    <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 achieve a cancer-cell-killing system with high specificity, we first took attention to a mechanism in the human immune system called membrane attack complex (MAC), which operates when bacteria infect our body. In the system of MAC, subunits penetrate the membrane, oligomerize, and form a pore into the bacteria membrane. Then the subunits disrupt the lipid bilayer, inducing targeted cells lysis and death. The point of this system is that the subunits show cytotoxity only after forming a pore. MAC do not kill the cell simply by penetration, as molecules on the surface of harmless cells prevent MAC from sticking in (and forming pores). Therefore, MAC will only show cytotoxity to foreign cells such as bacteria. 　　　　</p>

       <br>

   </article>

    <article>
      <p class="paragraph">

However, the target-recognition of MAC is far more complicated than referred above, in which a lot of molecules are related. So it is much difficult to mimic the whole system, leading us to take a simple synthetic biological approach.

      </p>

      <figure>
        <center>
          <img src="http://openwetware.org/images/f/f8/Todai_solution3.2.png" width=450px height=350px >
        </center>
      </figure>
    </article>
   <br>

    <article>

      <p class="paragraph">

In the previous study, Rausch et al. used peptides 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 recognize the specific cells. To achieve the recognition system, we thought about using DNA. Recently, in situ computation by DNA was reported (Maria Rudchenko et al. (2013).<span class="ref-sup"><a href="#proref-2">[2]</a></span> In that study, DNA was used as logic circuits: using surface antigens as inputs and generating DNA strands as outputs. Rudchenko et al. said that it may be possible to use their logic circuit for other self-assembling systems and DNA machinery. We, therefore, thought that it might be possible to make cancer-recognition system using DNA. Inspired by cell recognizing molecular nano-robot study (Douglass et al. (2012)<span class="ref-sup"><a href="#proref-3">[3]</a></span>, we used <a href="http://openwetware.org/wiki/Biomod/2013/Todai/Design#2.2_Recognition_system" style="color:#e00000">DNA aptamer</a> to recognize cancer cells.

      </a>.. 
      </p>

      <br>
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   </article>

    <article>
      <p class="paragraph">
Our general idea is explained as follows. 1) Subunits stick in normal and cancer cells nonspecifically. 2) In case that cancer-specific proteins exist, OCKs get able to oligomerize. 3)Then subunits oligomerize and form a pore, and cytotoxicity is induced to the cancer cell. Overall, our subunits may oligomerize only on the cancer cells and kill only cancer cells.
      </p>
      
      <p class="paragraph">

DNA itself has information embedded in the sequence. Using DNA computation and DNA-protein hybrid system, in which multiple molecules coordinate, we believe that our "Oligomeric Cell Killer" has the potential to treat cancer and other diseases like infection.

      </p>
      <br>

    <figure>
      <center>
        <img src="http://openwetware.org/images/d/d8/Todai_solution3.3.png" width=450px height=350px >
       </center>
     </figure>
   </article>
   <br>

 </article>
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  <article>
   <h1 class="title"><a name="Project Goals">&nbsp;Project Goals</a></h1>

    <article>
      <p class="paragraph">
We set the creation of a prototype of<a style="color:#e00000"> the cancer-specific drug which doesn't need delivery system (DDS)</a> as the goal.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>

   </article>
   <br>

    <article>
      <p class="paragraph">
      We can divide the project goal 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 solution.</li>
      <li>Subunits penetrate into the membrane.</li>
      <li>Subunits recognize cancer-specific proteins.</li>
      <li>Subunits oligomerize and form a pore on the membrane.</li>
    </ul>

    <figure>
      <center>
        <img src="http://openwetware.org/images/4/4f/Projectsteps.png" width="750px" height="500px" style="position:relative;left:-22px;" >
       </center>
     </figure>
    </article>
    <br>

      <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>

  <article>
    <h1 class="title"><a name="References">&nbsp;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 &amp; 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]A logic-gated nanorobot for targeted transport of molecular payloads.
       </a>
       </div>
          <div class="reference-author">
         Shawn M. Douglas, Ido Bachelet and George M. Church
          </div>
             <div class="reference-journal">
           Science. 2012 Feb 17;335(6070):831-4. doi: 10.1126/science.1214081.
             </div>
    </div>
 </article>
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