Team:Brown

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<center> <font size="36"><font color="blue"> Brown University iGEM 2009 </font size> </font color><p>
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{| style="color:#1b2c8a;background-color:white;" cellpadding="3" cellspacing="1" border="1" bordercolor="#fff" width="62%" align="center"
 
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!align="center"|[[Team:Brown|Home]]
 
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!align="center"|[[Team:Brown/Team|The Team]]
 
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!align="center"|[[Team:Brown/Project|The Project]]
 
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!align="center"|[[Team:Brown/Parts|Parts Submitted to the Registry]]
 
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!align="center"|[[Team:Brown/Modeling|Modeling]]
 
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!align="center"|[[Team:Brown/Notebook|Notebook]]
 
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|The 2009 Brown iGEM Team consists of 9 undergraduates from diverse backgrounds in science and engineering. We are mentored by Brown graduate students, postdocs, iGEM alumni, and faculty. With support from Brown UTRA Scholarships, we are working on our project in the Multi Disciplinary Lab over the summer.
 
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This year's team members are:
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[[Image:Brownbanner.gif|center|800px]]
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Will Allen '12,
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Michael Chang '11,
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Stephanie Cheung '11,
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Ashley Kim '11,
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Flora Ko '12,
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Minoo Ramanathan '11,
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Ahmad Rana '11,
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Elias Scheer '12,
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Indu Voruganti '12
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Every year, over '''<big>fifty million people</big>''' in the US suffer from '''<big>allergic rhinitis</big>''',
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the most common type of allergy. Allergens such as pollen, dust, and dander result in nasal congestion, itching, burning, sneezing, and overall '''<big>discomfort</big>'''. Current treatments include over-the-counter '''<big>antihistamines</big>''', however, side effects of these drugs include drowsiness, restlessness, and poor concentration. For patients suffering from chronic allergies and inflammation, there is a great '''<big>need for an alternative strategy</big>''' for combating allergic symptoms '''<big>without</big>''' causing '''<big>significant side effects</big>'''.
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The 2009 Brown iGEM Team aims to treat allergic rhinitis by engineering Staphylococcus epidermidis to secrete a histamine binding protein in response to elevated histamine concentrations during an allergic attack. The histamine-binding protein, rEV131, has been cloned from a species of tick, Rhipicephalus appendiculatus. rEV131 binds histamine with an extremely high affinity, and normally functions to prevent the inflammatory response while the tick sucks blood. We are transforming the gene coding for rEV131 into an S. epidermidis, which is endogenous in the human nasal flora. rEV131 will have a secretion tag specific for S. epidermidis.
 
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Additionally, to synchronize rEV131 production with elevation of histamine, we are engineering a novel histamine receptor by carrying out site-directed mutagenesis on Taz1, a fusion protein that contains a periplasmic receptor region and a transmembrane and cytoplasmic regions. The transmembrane and cytoplasmic regions are responsible for a signal transduction pathway that links to gene transcription. The eventual goal is to link this histamine-responsive receptor to activation of an operon that promotes transcription of rEV131.
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The '''<big>2009 Brown University iGEM</big>''' team worked to treat allergic rhinitis by '''<big>engineering Staphylococcus epidermidis</big>''', a microbe endogenous to the human nasal flora, to '''<big>secrete</big>''' a recombinant '''<big>histamine-binding protein</big>''' in response to the elevated histamine concentrations of an allergic response.  The engineered strain of S. epidermidis will function as a '''<big>self-regulating drug factory in the nose</big>''', providing relief, '''<big>without</big>''' any negative '''<big>side effects</big>'''.
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Although S. epidermidis is a non-pathogenic specimen, additional safety precautions are being taken to control over-proliferation. When S. epidermidis reaches a certain population threshold, it begins to produce hazardous biofilms. We have cloned this population sensor, however, and placed its promoter over a DNA gyrase poison, cuing its "suicide" when populations have reached a dangerous level.
 
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    <td width="165" height="107"><center><a href="https://2009.igem.org/Team:Brown/Team"><img src="https://static.igem.org/mediawiki/2009/8/8c/Teambutton.gif" width="168" height="100" align="absmiddle" longdesc="https://static.igem.org/mediawiki/2009/8/8c/Teambutton.gif"></td>
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    <td width="164" height="107"><center><a href="https://2009.igem.org/Team:Brown/Parts"><img src="https://static.igem.org/mediawiki/2009/3/33/Partsbutton.gif" alt="" width="161" height="100" longdesc="https://static.igem.org/mediawiki/2009/3/33/Partsbutton.gif"></td>
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      <td width="154" height="107"><center><a href="https://2009.igem.org/Team:Brown/Notebook_Weekly_Logs"><img src="https://static.igem.org/mediawiki/2009/c/ce/Notebookbutton.gif" width="157" height="100"></td>
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<td width="154"><center><a href="https://2009.igem.org/Team:Brown/Project_Introduction"><img src="https://static.igem.org/mediawiki/2009/6/6e/Learnmoreallergiesbutton.gif" alt="" width="150" height="100" longdesc="https://static.igem.org/mediawiki/2009/6/6e/Learnmoreallergiesbutton.gif"></td>
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<td width="156"><center><a href="https://2009.igem.org/Team:Brown/Project_Implications"><img src="https://static.igem.org/mediawiki/2009/9/97/Implicationsbutton.gif" alt="" width="157" height="100" longdesc="https://static.igem.org/mediawiki/2009/9/97/Implicationsbutton.gif"></td>
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    <td colspan="2"><a href="https://2009.igem.org/Team:Brown/Project"><img src="https://static.igem.org/mediawiki/2009/2/2a/Projectabstractbutton.gif" width="335" height="100"></td>
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<!--- The Mission, Experiments --->
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    <td colspan="3">&nbsp;<i>Learn more about Allergene: a synthetically engineered, self-regulating drug factory in the &nbsp;nose.</i> </td>
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    <td colspan="2"><a href="https://2009.igem.org/Team:Brown/Project_Histamine_Sensor"><img src="https://static.igem.org/mediawiki/2009/d/d0/Histaminesensorbutton.gif" width="335" height="100"></td>
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    <td colspan="3">&nbsp;<i>When an allergic response occurs, our system senses a change in histamine levels above &nbsp;threshold and initiates an intracellular cascade, signaling cells to respond appropriately to &nbsp;the increase in histamine concentration.</i> </td>
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    <td colspan="2"><a href="https://2009.igem.org/Team:Brown/Project_HBP"><img src="https://static.igem.org/mediawiki/2009/7/70/Hbpbutton.gif" alt="" width="335" height="100"></td>
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    <td colspan="3">&nbsp;<i>EV131 is a high-affinity histamine binding protein, that originates from the saliva of a &nbsp;female tick species.</i> </td>
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      <td colspan="2"><a href="https://2009.igem.org/Team:Brown/Project_S.epidermidis"><img src="https://static.igem.org/mediawiki/2009/3/3c/S.epibutton.gif" alt="" width="335" height="100"></td>
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    <td colspan="3">&nbsp;<i>The chassis of choice  for production and secretion of the Histamine Binding Protein is &nbsp;Staphyloccocus Epidermidis, an organism endogenous to the human nasal flora. A quorum &nbsp;sensing mechanism was also incorporated to regulate cell density.</i>  </td>
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    <td colspan="2"><a href="https://2009.igem.org/Team:Brown/Project_All_Together"><img src="https://static.igem.org/mediawiki/2009/1/12/Alltogetherbutton.gif" alt="All Together" width="335" height="100"></a></td>
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    <td colspan="3">&nbsp;<i>What happens when an allergy attacks: Description of the overall construct mechanism in &nbsp;S.epidermidis incorporating the histamine sensor, intracellular signal cascade, and &nbsp;transcription of EV131 ligated to secretion peptide.  </i> </td>
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                    '''A special thank you to Team Heidelberg for inspiring our wiki design!'''

Latest revision as of 03:07, 22 October 2009




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Every year, over fifty million people in the US suffer from allergic rhinitis, the most common type of allergy. Allergens such as pollen, dust, and dander result in nasal congestion, itching, burning, sneezing, and overall discomfort. Current treatments include over-the-counter antihistamines, however, side effects of these drugs include drowsiness, restlessness, and poor concentration. For patients suffering from chronic allergies and inflammation, there is a great need for an alternative strategy for combating allergic symptoms without causing significant side effects.


The 2009 Brown University iGEM team worked to treat allergic rhinitis by engineering Staphylococcus epidermidis, a microbe endogenous to the human nasal flora, to secrete a recombinant histamine-binding protein in response to the elevated histamine concentrations of an allergic response. The engineered strain of S. epidermidis will function as a self-regulating drug factory in the nose, providing relief, without any negative side effects.



 Learn more about Allergene: a synthetically engineered, self-regulating drug factory in the  nose.
 When an allergic response occurs, our system senses a change in histamine levels above  threshold and initiates an intracellular cascade, signaling cells to respond appropriately to  the increase in histamine concentration.
 EV131 is a high-affinity histamine binding protein, that originates from the saliva of a  female tick species.
 The chassis of choice for production and secretion of the Histamine Binding Protein is  Staphyloccocus Epidermidis, an organism endogenous to the human nasal flora. A quorum  sensing mechanism was also incorporated to regulate cell density.
All Together  What happens when an allergy attacks: Description of the overall construct mechanism in  S.epidermidis incorporating the histamine sensor, intracellular signal cascade, and  transcription of EV131 ligated to secretion peptide.



                    A special thank you to Team Heidelberg for inspiring our wiki design!