Team:UC Davis

From 2009.igem.org

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An estimated one in every 133 Americans suffer from an autoimmune disorder called celiac disease (14, 11). Celiac disease is a condition in which the small intestines are unable to digest gliadin, a protein present in gluten. When gliadin is consumed by an individual with celiac disease, the immune system responds by causing a range of side-effects, which may include abdominal pain, chronic diarrhea, and/or vomiting (14). A friend of one of our teammates currently suffers from this illness, which prompted 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 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 would prevent gliadin from progressing through the small intestine and inducing immune system response.
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This synthetically engineered organism should be able to satisfy two main criteria. First, it should be able to survive ''only'' in the stomach and secondly, it should 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 are being used in recent studies regarding treatment for celiac disease.
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Due to licensing restrictions, we have opted not to work with this protein.
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<div style="text-align: center;"><span
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style="color: rgb(255, 255, 153);">&nbsp;
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We have decided to focus our summer project on building two key elements required for our desired organism:
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</span><b style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><span
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# An inducible secretion system
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style="color: rgb(255, 255, 153);"><img src="" alt=""
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# A biological pH sensor limiting this secretion system to the stomach
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style="color: rgb(255, 255, 153);"><span
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The pH system would sense the pH change when the probiotic organism leaves the stomach and prompt apoptosis to occur.
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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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[[https://2009.igem.org/Team:UC_Davis/About_Us About Us]] [[https://2009.igem.org/Team:UC_Davis/Celiac Celiac Disease]] [[https://2009.igem.org/Team:UC_Davis/Treatments Current Treatment]] [[https://2009.igem.org/Team:UC_Davis/Approach Our Approach]] [[https://2009.igem.org/Team:UC_Davis/pH_Sensor pH Sensor]] [[https://2009.igem.org/Team:UC_Davis/pH_Sensor/parts pH Sensor Parts]] [[https://2009.igem.org/Team:UC_Davis/pH_Sensor/promoters pH Promoters]] [[https://2009.igem.org/Team:UC_Davis/Secretion/parts Secretion Parts]]
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href="https://2009.igem.org/Team:UC_Davis/About_Us"><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></a><b
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><a
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href="https://2009.igem.org/Team:UC_Davis/About_Us"><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></a><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big>&nbsp;
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</big></big></big></big></span></b><b style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big><a
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href="https://2009.igem.org/Team:UC_Davis/About_Us"><img alt=""
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src="https://static.igem.org/mediawiki/2009/d/d1/UCDAVIS_PIC4.png"
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style="border: 0px solid ; width: 92px; height: 46px;"></a> </big></big></big></big></span></b><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big><a
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href="https://2009.igem.org/Team:UC_Davis/Project"><img alt=""
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src="https://static.igem.org/mediawiki/2009/b/b9/UCDAVIS_PIC8.png"
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style="border: 0px solid ; width: 92px; height: 46px;"></a> </big></big></big></big></span></b><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big><a
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href="https://2009.igem.org/Team:UC_Davis/Notebook"><img alt=""
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src="https://static.igem.org/mediawiki/2009/2/2f/UCDAVIS_PIC5.png"
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style="border: 0px solid ; width: 92px; height: 46px;"></a> </big></big></big></big></span></b><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><b
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style="color: rgb(255, 255, 153);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big><a
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href="https://2009.igem.org/Team:UC_Davis/Parts"><img alt=""
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src="https://static.igem.org/mediawiki/2009/a/a6/UCDAVIS_PIC6.png"
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style="border: 0px solid ; width: 92px; height: 46px;"></a>&nbsp;<a
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href="https://2009.igem.org/Team:UC_Davis/Contacts_References"><img
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alt="" src="https://static.igem.org/mediawiki/2009/1/1d/UCDAVIS_PIC7.png"
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style="border: 0px solid ; width: 92px; height: 46px;"></a></big></big></big></big></span></b><b
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style="color: rgb(0, 0, 0);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big><big><big><big><small>
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<img style="width: 191px; height: 147px;" alt="" src=""><br>
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</small></big></big></big></big></span></b></div>
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<hr style="width: 100%; height: 2px;"><b style="color: rgb(0, 0, 0);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><big><span
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style="color: rgb(0, 0, 0);"></span></big><b
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style="color: rgb(0, 0, 0);"><span
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style="font-size: 13pt; line-height: 115%; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><span
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style="font-family: Symbol;"></span><span
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style="font-family: Arial Narrow; font-weight: bold;"></span></span></b><span
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style="color: rgb(0, 0, 0); font-family: Arial Narrow; font-weight: bold;"><span
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style="font-size: 13pt; line-height: 115%;"></span></span>
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<p class="MsoNormal"
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style="margin-bottom: 0.0001pt; line-height: normal;"><b><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;; color: black;">&nbsp;&nbsp;&nbsp;
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&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;<big> </big></span></b><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;; color: black; font-weight: bold;"><big>&nbsp;
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</big><big>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 in which the small intestines of
 +
an
 +
affected individual cannot properly digest gliadin, a protein present
 +
in gluten.
 +
When
 +
consumed, gliadin induces immune system responses, the
 +
side-effects of which are,
 +
but not limited to: abdominal pain, chronic diarrhea, and vomiting (14).
 +
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 imagine an alternative
 +
treatment based on a probiotic organism
 +
that can
 +
survive and take residence in the stomach, where it would secrete an
 +
enzyme that
 +
degrades gliadin.</big></span><big style="font-weight: bold;"><span
 +
style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><br>
 +
&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; &nbsp;&nbsp; Then the design
 +
elements of this organism should satisfy at least two main
 +
criteria.
 +
First, it
 +
should be able to survive only in the stomach; second, it should secrete an
 +
enzyme
 +
that degrades gliadin<i>.</i> We envision that these parts would
 +
not
 +
only be useful for our project, but also to other future projects.</span><span
 +
style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><o:p></o:p></span><br>
 +
</big><span style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big
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style="font-weight: bold;">&nbsp;&nbsp;&nbsp;
 +
&nbsp; &nbsp;
 +
&nbsp;&nbsp; We decided to focus our summer project on building the
 +
first of the two key elements
 +
required for
 +
our system:<o:p></o:p><br>
 +
&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;
 +
&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; 1. <a
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href="https://2009.igem.org/Team:UC_Davis/secretion">Produce an
 +
inducible secretion
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system</a><br>
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</big>
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<big style="font-weight: bold;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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2. <a href="https://2009.igem.org/Team:UC_Davis/ph_sensor1">Construct a
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biological pH sensor limiting this secretion system to
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the
 +
stomach</a></big></span><a
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href="https://2009.igem.org/Team:UC_Davis/ph_sensor1"><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><span
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style="text-decoration: underline;"></span></span></a><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><big
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style="font-weight: bold;"><br>
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</big></span></p>
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<p class="MsoNormal"
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style="margin-bottom: 0.0001pt; line-height: normal;"><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span><a
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href="https://2009.igem.org/Team:UC_Davis/ph_sensor1"><b
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style="color: rgb(0, 0, 0);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></a><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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&nbsp;</span><a href="https://2009.igem.org/Team:UC_Davis/ph_sensor1"><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><span
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style="text-decoration: underline;"></span></span></a><a
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href="https://2009.igem.org/Team:UC_Davis/Project_Summary"><img alt=""
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src="https://static.igem.org/mediawiki/2009/a/ac/UCDAVIS_summary.png"
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style="border: 0px solid ; width: 63px; height: 50px;"></a><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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<span style="text-decoration: underline;"><br>
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</span> </span><a href="https://2009.igem.org/Team:UC_Davis/ph_sensor1"><b
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style="color: rgb(0, 0, 0);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></a><span
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style="font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span><b
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style="color: rgb(0, 0, 0);"><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></p>
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<hr style="width: 100%; height: 2px;">
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<p class="MsoNormal"
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style="margin-bottom: 0.0001pt; line-height: normal; color: rgb(0, 0, 0); text-align: center; background-color: rgb(255, 255, 255);"><b><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><b><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><b><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b><b><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"></span></b></p>
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<ul style="background-color: rgb(255, 255, 255); color: rgb(0, 0, 0);">
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</ul>
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<div style="text-align: center;"><big> </big></div>
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<div style="text-align: center;">
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<div style="text-align: left;">
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<div style="text-align: center;"><big><span style="font-weight: bold;"><big>&nbsp;&nbsp;
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&nbsp;&nbsp;<small>
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UC
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Davis iGEM team is sponsored by:</small></big></span></big><br>
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<big><span style="font-weight: bold;"></span></big></div>
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<div style="text-align: center;">&nbsp;&nbsp; &nbsp;&nbsp; <img
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src="https://static.igem.org/mediawiki/2009/8/88/UCDAVIS_Biomedical_engineering.jpg"
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alt="" style="width: 83px; height: 109px;"><img
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style="width: 105px; height: 109px;" alt=""
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src="https://static.igem.org/mediawiki/2009/4/43/UCDAVIS_college_of_engineering.png"><img
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style="width: 135px; height: 99px;" alt=""
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src="https://static.igem.org/mediawiki/2009/8/8e/UCDAVIS_Accutek1.jpg"><img
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style="width: 121px; height: 109px;" alt=""
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src="https://static.igem.org/mediawiki/2009/6/6b/UCDAVIS_mrgen.gif"><img
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style="width: 182px; height: 108px;" alt=""
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src="https://static.igem.org/mediawiki/2009/c/c6/UCDAVIS_genome_center.jpg"><br>
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<font size="-1">We want to thank <span style="font-weight: bold;">Marc</span>
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<span style="font-weight: bold;">Facciotti</span> for his helpful
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advice.<br>
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Special thanks to <span style="font-weight: bold;">Suzy
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Fenton</span>,<span style="font-weight: bold;">Wayne Fenton, Jeanne
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Joe-Fenton </span>and<span style="font-weight: bold;"> Wayne Fenton Jr.</span>
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<br>
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Also we thank <span style="font-size: 10pt; line-height: 115%;"><b>Charles
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H. <span class="il">Halsted </span></b><span class="il">for reviewing
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our material regarding celiac disease.</span></span></font><br>
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<br>
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</div>
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</div>
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</div>
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<ul style="background-color: rgb(255, 255, 255); color: rgb(0, 0, 0);">
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<span style="font-weight: bold;"></span>
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</ul>
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<p class="MsoNormal"
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style="margin-bottom: 0.0001pt; line-height: normal; color: rgb(0, 0, 0); text-align: left; background-color: rgb(255, 255, 255);"><b><span
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style="font-size: 13.5pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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</span></b></p>
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<span style="color: rgb(0, 0, 0);"></span>
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</body>
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</html>

Latest revision as of 18:07, 21 October 2009

Homepage_UCdavis

     

              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 in which the small intestines of an affected individual cannot properly digest gliadin, a protein present in gluten. When consumed, gliadin induces immune system responses, the side-effects of which are, but not limited to: abdominal pain, chronic diarrhea, and vomiting (14). 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 imagine an alternative treatment based on a probiotic organism that can survive and take residence in the stomach, where it would secrete an enzyme that degrades gliadin.
           Then the design elements of this organism should satisfy at least two main criteria. First, it should be able to survive only in the stomach; second, it should secrete an enzyme that degrades gliadin. We envision that these parts would not only be useful for our project, but also to other future projects.
           We decided to focus our summer project on building the first of the two key elements required for our system:
                1. Produce an inducible secretion system
                 2. Construct a biological pH sensor limiting this secretion system to the stomach

                                                                                                                                                                                                                                                                                                                                  

      UC Davis iGEM team is sponsored by:
     
We want to thank Marc Facciotti for his helpful advice.
Special thanks to Suzy Fenton,Wayne Fenton, Jeanne Joe-Fenton and Wayne Fenton Jr.
Also we thank Charles H. Halsted for reviewing our material regarding celiac disease.

                                         

Retrieved from "http://2009.igem.org/Team:UC_Davis"