Team:HKUST-Hong Kong/Expectation

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               <div class="Content_Buttons"><p><a href="https://2012.igem.org/Team:HKUST-Hong_Kong/Project_Abstraction">Project Abstract</a></p></div>
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              <div class="Content_Buttons"><p><a href="https://2012.igem.org/Team:HKUST-Hong_Kong/Background_and_Motive">Background and<br> Motive</a></p></div>
 
               <div class="Content_Buttons"><p><a href="https://2012.igem.org/Team:HKUST-Hong_Kong/Project">Project Description</a></p></div>
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              <div class="Content_Buttons"><p><a href="https://2012.igem.org/Team:HKUST-Hong_Kong/Background_and_Motive">Background and<br> Motive</a></p></div>
               <div class="Content_Buttons"><p><a href="https://2012.igem.org/Team:HKUST-Hong_Kong/Module">Module</a></p></div>
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           <p>Through assembly of the target binding  module, anti-tumor drug synthesis module and regulatory module, we would to introduce our genetically engineered <i>Bacillus subtilis</i>, B. hercules, as an  anti-colon-tumor agent to provide direct tumoricidal effect during cancer  therapy. It is applied as<u> oral medicine</u> which retains viability through  digestive tract and executes anti-tumor activity when and only when it is  binding to colon cancer cell. </p>
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<p>Driven by pVeg constitutive promoter,  RPMrel, the colon-tumor specific peptide will be displayed on the cell wall of  B. hercules under the facilitation of LytC cell wall displaying system before it is orally intake. When B. Hercules is taken orally by patient, it is expected to reach colon after <strong>8 hours</strong> without  retaining or colonizing in gastrointestinal tract. However, once it reaches  colon, it will be held up around colon tumor cells and colonize around them, waiting  for signal to produce anti-tumor molecule, BMP2 to the local environment. <br />
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           <p>Through assembly of the target binding  module, anti-tumor drug synthesis module and regulatory module, we would  introduce our genetically engineered <i>Bacillus subtilis</i>, B. hercules, as an  anti-colon-tumor agent to provide direct tumoricidal effect during cancer  therapy. It would be applied as an <u>oral medicine</u> which should retain viability in digestive tract and execute anti-tumor activity when and only when it binds to colon cancer cell. </p>
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  Since  the expression of BMP2 is controlled by xylose inducible promoter and no xylose is present in colon, xylose is taken orally or injected from anus to induce the  production of BMP2 when B. Hercules has successfully localized around colon  tumor. The locally concentrated BMP2 is expected to suppress colon tumor grow  and trigger the apoptosis of tumor while the low level BMP2 in colon introduces  as little adverse effect as possible to normal colon tissues. <br />
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<p>Driven by pVeg constitutive promoter,  RPMrel, the colon-tumor specific peptide should be displayed on the cell wall of  B. hercules under the facilitation of LytC cell wall displaying system before oral ingestion. Once ingested, B. Hercules would be expected to reach colon after <strong>8 hours</strong> without  retaining in or colonizing the gastrointestinal tract. However, upon reaching the colon, it should hold up around colon tumor cells and colonize around them, and should await signals to produce anti-tumor molecule, BMP-2, which would be released to the local environment. </p>
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  When  BMP2 is intensively produced under the inducing from xylose, controlling by the  same promoter, the expression of toxin ydcE will overwhelm the protection  threshold from antitoxin ydcD. The overexpression of toxin with BMP2 production  is to cause the suicide of B. hurcules and prevent any adverse effect from BMP  overdose.</p>
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<p>The expression of BMP-2 would be controlled by xylose inducible promoter. Since normally no xylose is present in colon, xylose would be taken orally or injected from anus. At that moment, B. Hercules should has successfully localized around colon  tumor, and the arriving xylose should induce the  production of BMP-2. The locally concentrated BMP-2 is expected to suppress colon tumor grow  and trigger the apoptosis of the tumor. The BMP-2 level in colon should be low, and should have little adverse effect on normal colon tissues.</p>
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<p>The concentration of xylose might overshoot, which might result in excessive production of BMP-2. If that happened, the excess xylose would induce high level of expression of the toxin YdcE. Once the amount of YdcE breaches the protection  threshold from antitoxin YdcD, uninhibited YdcE will lead to the destruction of B. hercules. This would hopefully avoid the overdosing effect of xylose and the overproduction of BMP-2, and their subsequent adverse effect.</p>
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Latest revision as of 14:30, 25 September 2012

Team:HKUST-Hong Kong - 2012.igem.org

EXPECTATION

Through assembly of the target binding module, anti-tumor drug synthesis module and regulatory module, we would introduce our genetically engineered Bacillus subtilis, B. hercules, as an anti-colon-tumor agent to provide direct tumoricidal effect during cancer therapy. It would be applied as an oral medicine which should retain viability in digestive tract and execute anti-tumor activity when and only when it binds to colon cancer cell.

Driven by pVeg constitutive promoter, RPMrel, the colon-tumor specific peptide should be displayed on the cell wall of B. hercules under the facilitation of LytC cell wall displaying system before oral ingestion. Once ingested, B. Hercules would be expected to reach colon after 8 hours without retaining in or colonizing the gastrointestinal tract. However, upon reaching the colon, it should hold up around colon tumor cells and colonize around them, and should await signals to produce anti-tumor molecule, BMP-2, which would be released to the local environment.

The expression of BMP-2 would be controlled by xylose inducible promoter. Since normally no xylose is present in colon, xylose would be taken orally or injected from anus. At that moment, B. Hercules should has successfully localized around colon tumor, and the arriving xylose should induce the production of BMP-2. The locally concentrated BMP-2 is expected to suppress colon tumor grow and trigger the apoptosis of the tumor. The BMP-2 level in colon should be low, and should have little adverse effect on normal colon tissues.

The concentration of xylose might overshoot, which might result in excessive production of BMP-2. If that happened, the excess xylose would induce high level of expression of the toxin YdcE. Once the amount of YdcE breaches the protection threshold from antitoxin YdcD, uninhibited YdcE will lead to the destruction of B. hercules. This would hopefully avoid the overdosing effect of xylose and the overproduction of BMP-2, and their subsequent adverse effect.