Team:UC Davis

From 2009.igem.org

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It is estimated that about one in every 133 Americans suffer from an autoimmune disorder called Celiac Disease (14, 11). Celiac Disease is a condition where the small intestines of an affected individual cannot digest gliadin, a protein present in gluten. When consumed, gliadin kick starts immune system responses, whose side-effects are, but not limited to abdominal pain, chronic diarrhea and vomiting (14). One of our teammate’s friends is currently suffering from this illness, which interested us to look into Celiac Disease as the focus of our project. Currently, the only accepted treatment for this disorder is adhering to a gluten-free diet (14, 12). This can be very difficult as great varieties of food contain gluten. This inspired us to design a probiotic organism that could survive and take residence in the stomach where it would secrete an enzyme that can degrade gliadin.
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This synthetically engineered bug should be able to satisfy at least two main criteria. First, it should be able to survive ONLY in the stomach and, secondly, secrete an enzyme that can degrade gliadin.  
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Studies have shown that the enzyme, Prolyl-endoprotease is able to degrade gliadin at the pH level of the stomach (8). Prolyl-endoprotease is one of the most promising enzymes which being used in recent studies regarding celiac disease treatment.
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Due to licensing restrictions, we have opted not to work with this protein.
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We have decided to focus our summer project on building two key elements required for our “dream bug”. Therefore, our project has been split into two tasks:
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# Produce an inducible secretion system
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# Construct a biological pH sensor limiting this secretion system to the stomach
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<big><big><span style="font-weight: bold;">Preliminary project
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This pH system will be sensitive to the change in pH when the probiotic leaves the stomach.
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description:</span></big></big><small><br>
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We are confident that our two systems can be built in time to present to the iGEM community.
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">1
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in 133 Americans are suffering
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from a form of autoimmune disorder called Celiac Disease. Celiac
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Disease is a
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condition where the small intestines of an affected individual cannot
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digest
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gliadin, a protein present in gluten. If consumed, the body kick starts
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its
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immune system response. The effects of the immune response include, but
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are not
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limited to abdominal pain and vomiting.</span><span
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<span style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span><br>
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<span style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">One
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of our teammate's friends is
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currently suffering from this illness, which
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prompted us to look into Celiac Disease as our main focus. What we
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learned that currently, no cure has been found and the only treatment
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is a gluton free diet.
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This treatment is very difficult as an overwhelming majority of food
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contain
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gluten and gliadin.</span><span
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<span style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">This
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year the University of
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California,Davis entered the 2009 iGEM competition with a focus on
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creating
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a new
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way to treat Celiac. Our project has been split into two tasks. The
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first is to
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produce an inducible secretion system; the second is to construct a
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biological
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pH sensor to compartmentalize this secretion system in the stomach.
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Moreover, this
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pH system will act as a kill switch if this system were to ever leave
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the
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stomach by inducing cell death via pH change. After weeks of reading
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numerous
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articles, we are confident that with correct parts and timing, our
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two
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systems can be built in time to present to the iGEM community.</span><span
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We
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have recently moved into the synthesis
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and assembly stage of our two systems.</span><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">Though
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this is our first year in the competition, we feel
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that we are moving at a good pace, working out kinks along the way.</span><o:p></o:p></p>
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Revision as of 03:12, 22 September 2009

Overview

It is estimated that about one in every 133 Americans suffer from an autoimmune disorder called Celiac Disease (14, 11). Celiac Disease is a condition where the small intestines of an affected individual cannot digest gliadin, a protein present in gluten. When consumed, gliadin kick starts immune system responses, whose side-effects are, but not limited to abdominal pain, chronic diarrhea and vomiting (14). One of our teammate’s friends is currently suffering from this illness, which interested us to look into Celiac Disease as the focus of our project. Currently, the only accepted treatment for this disorder is adhering to a gluten-free diet (14, 12). This can be very difficult as great varieties of food contain gluten. This inspired us to design a probiotic organism that could survive and take residence in the stomach where it would secrete an enzyme that can degrade gliadin.

This synthetically engineered bug should be able to satisfy at least two main criteria. First, it should be able to survive ONLY in the stomach and, secondly, secrete an enzyme that can degrade gliadin.

Studies have shown that the enzyme, Prolyl-endoprotease is able to degrade gliadin at the pH level of the stomach (8). Prolyl-endoprotease is one of the most promising enzymes which being used in recent studies regarding celiac disease treatment.

Due to licensing restrictions, we have opted not to work with this protein.

We have decided to focus our summer project on building two key elements required for our “dream bug”. Therefore, our project has been split into two tasks:

  1. Produce an inducible secretion system
  2. Construct a biological pH sensor limiting this secretion system to the stomach

This pH system will be sensitive to the change in pH when the probiotic leaves the stomach. We are confident that our two systems can be built in time to present to the iGEM community.