Chloroplast (Talk | contribs) |
Chloroplast (Talk | contribs) |
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<div id="st-trigger-effects"> | <div id="st-trigger-effects"> | ||
− | <button data-effect="st-effect-1" class="button button--rayen button--border button--round-m" data-text="More" style="z-index: 100"> | + | <button data-effect="st-effect-1" class="button button--rayen button--border button--round-m" data-text="More" style="left: -83px; font-size: 50px; z-index: 100"> |
<span><img src="https://static.igem.org/mediawiki/2016/c/ce/T--NUS_Singapore--scroll-down-arrow.png"></span> | <span><img src="https://static.igem.org/mediawiki/2016/c/ce/T--NUS_Singapore--scroll-down-arrow.png"></span> | ||
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<div class="ha-header-bottom" style="text-align: center;"> | <div class="ha-header-bottom" style="text-align: center;"> | ||
− | <a><h1><a href="https://2016.igem.org/Team:NUS_Singapore" style="color: black; font-weight: lighter;">iGEM 2016 | + | <a><h1><a href="https://2016.igem.org/Team:NUS_Singapore" style="color: black; font-weight: lighter;">iGEM 2016 NUS_SINGAPORE</a></h1></a> |
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− | <nav class="st-menu st-effect-1 list-group panel" id="menu-1" style="overflow: auto; z-index: 100; background-color: | + | <nav class="st-menu st-effect-1 list-group panel" id="menu-1" style="overflow: auto; z-index: 100; background-color: #E59500;"> |
+ | <span><img src="https://static.igem.org/mediawiki/2016/1/1e/T--NUS_Singapore--practice.png" style="width: 30px; height: auto; top: 35px; left: 35px; position: absolute;"><h4 style=" left: 75px; top: 25px; position: absolute; font-size: 17px; color: white;">NUS_SINGAPORE</h4></span> | ||
<ul> | <ul> | ||
<li><a class="icon icon-home" id="menu-item-1" href="https://2016.igem.org/Team:NUS_Singapore">Home</a></li> | <li><a class="icon icon-home" id="menu-item-1" href="https://2016.igem.org/Team:NUS_Singapore">Home</a></li> | ||
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<div class="grow" id="grow-2"> | <div class="grow" id="grow-2"> | ||
<div class='measuringWrapper'> | <div class='measuringWrapper'> | ||
− | <a href="https://2016.igem.org/Team:NUS_Singapore/Project/Wet_Lab" class="list-group-item" style="color: rgb(179, 179, 179);"> | + | <a href="https://2016.igem.org/Team:NUS_Singapore/Project/Wet_Lab" class="list-group-item" style="color: rgb(179, 179, 179);">Overview</a> |
− | <a href="https://2016.igem.org/Team:NUS_Singapore/ | + | |
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/Model" class="list-group-item" style="color: rgb(179, 179, 179);">Modelling</a> | ||
</div> | </div> | ||
</div> | </div> | ||
</li> | </li> | ||
+ | <li><a class="icon icon-notebook" id="menu-item-9" onclick="growDiv('9')" href="https://2016.igem.org/Team:NUS_Singapore/Notebook">RIOT Sensor | ||
+ | <span><img id="sidebar-arrow-9" src="https://static.igem.org/mediawiki/2016/c/ce/T--NUS_Singapore--scroll-down-arrow.png" style="position: relative; height: 20px; float: right;"></span></a> | ||
+ | <div class="grow" id="grow-9"> | ||
+ | <div class='measuringWrapper'> | ||
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/Description" class="list-group-item" style="color: rgb(179, 179, 179);">Description</a> | ||
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/Proof" class="list-group-item" style="color: rgb(179, 179, 179);">Proof of Concept</a> | ||
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/Demonstrate" class="list-group-item" style="color: rgb(179, 179, 179);">Demonstration</a> | ||
+ | |||
+ | </div> | ||
+ | </div> | ||
+ | </li> | ||
+ | <li><a class="icon icon-notebook" id="menu-item-5" href="https://2016.igem.org/Team:NUS_Singapore/RIOTResponder">RIOT Responder</a></li> | ||
+ | <li><a class="icon icon-notebook" id="menu-item-5" href="https://2016.igem.org/Team:NUS_Singapore/RIOTInvader">RIOT Invader</a></li> | ||
<li><a class="icon icon-practice" onclick="growDiv('3')" id="menu-item-3" href="#">Human Practices | <li><a class="icon icon-practice" onclick="growDiv('3')" id="menu-item-3" href="#">Human Practices | ||
<span><img id="sidebar-arrow-3" src="https://static.igem.org/mediawiki/2016/c/ce/T--NUS_Singapore--scroll-down-arrow.png" style="position: relative; height: 20px; float: right;"><span></a> | <span><img id="sidebar-arrow-3" src="https://static.igem.org/mediawiki/2016/c/ce/T--NUS_Singapore--scroll-down-arrow.png" style="position: relative; height: 20px; float: right;"><span></a> | ||
<div class="grow" id="grow-3"> | <div class="grow" id="grow-3"> | ||
<div class='measuringWrapper'> | <div class='measuringWrapper'> | ||
− | + | <a href="https://2016.igem.org/Team:NUS_Singapore/HP/Silver" class="list-group-item" style="color: rgb(179, 179, 179);">Survey</a> | |
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/HP/Gold" class="list-group-item" style="color: rgb(179, 179, 179);">Business Plan</a> | ||
+ | <a href="https://2016.igem.org/Team:NUS_Singapore/Integrated_Practices" class="list-group-item" style="color: rgb(179, 179, 179);">Integration</a> | ||
</div> | </div> | ||
</div> | </div> | ||
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<div class='measuringWrapper'> | <div class='measuringWrapper'> | ||
− | <a href="#" class="list-group-item" style="color: rgb(179, 179, 179);"> | + | <a href="https://2016.igem.org/Team:NUS_Singapore/Collaborations#MELBOURNE" class="list-group-item" style="color: rgb(179, 179, 179);">MELBOURNE</a> |
− | <a href="#" class="list-group-item" style="color: rgb(179, 179, 179);"> | + | <a href="https://2016.igem.org/Team:NUS_Singapore/Collaborations#HONG_KONG_HKUST" class="list-group-item" style="color: rgb(179, 179, 179);">HONG_KONG_HKUST</a> |
− | <a href="#" class="list-group-item" style="color: rgb(179, 179, 179);"> | + | <a href="https://2016.igem.org/Team:NUS_Singapore/Collaborations#HONG_KONG_HKU" class="list-group-item" style="color: rgb(179, 179, 179);">HONG_KONG_HKU</a> |
</div> | </div> | ||
</div> | </div> | ||
</li> | </li> | ||
+ | <li><a class="icon icon-notebook" id="menu-item-5" href="https://2016.igem.org/Team:NUS_Singapore/Parts">Parts Registry</a></li> | ||
<li><a class="icon icon-safety" id="menu-item-5" href="https://2016.igem.org/Team:NUS_Singapore/Safety">Safety</a></li> | <li><a class="icon icon-safety" id="menu-item-5" href="https://2016.igem.org/Team:NUS_Singapore/Safety">Safety</a></li> | ||
+ | |||
<li><a class="icon icon-team" id="menu-item-6" href="https://2016.igem.org/Team:NUS_Singapore/Team">Team</a></li> | <li><a class="icon icon-team" id="menu-item-6" href="https://2016.igem.org/Team:NUS_Singapore/Team">Team</a></li> | ||
<li><a class="icon icon-notebook" id="menu-item-7" onclick="growDiv('7')" href="https://2016.igem.org/Team:NUS_Singapore/Notebook">Notebook | <li><a class="icon icon-notebook" id="menu-item-7" onclick="growDiv('7')" href="https://2016.igem.org/Team:NUS_Singapore/Notebook">Notebook | ||
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</li> | </li> | ||
<li><a class="icon icon-acknowledgement" id="menu-item-8" href="https://2016.igem.org/Team:NUS_Singapore/Attributions">Attributions</a></li> | <li><a class="icon icon-acknowledgement" id="menu-item-8" href="https://2016.igem.org/Team:NUS_Singapore/Attributions">Attributions</a></li> | ||
+ | <li><a class="icon icon-cup" id="menu-item-8" href="https://2016.igem.org/Team:NUS_Singapore/Medals">Medals</a></li> | ||
</ul> | </ul> | ||
</nav> | </nav> | ||
− | <!--End of Side Bar--> | + | <!--End of Side Bar--> |
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<section style="background: black; position: relative; display: inline-block; overflow: hidden; height: 158%; width: 100%; padding-bottom: 3em; margin-bottom: -0.4em;"> | <section style="background: black; position: relative; display: inline-block; overflow: hidden; height: 158%; width: 100%; padding-bottom: 3em; margin-bottom: -0.4em;"> | ||
<img class="static" src="https://static.igem.org/mediawiki/2016/8/84/T--NUS_Singapore--banner.jpg" alt="Background" style="z-index: -1; position: fixed; opacity: 1; margin-top: 8%; width:100%; height: auto;" /> | <img class="static" src="https://static.igem.org/mediawiki/2016/8/84/T--NUS_Singapore--banner.jpg" alt="Background" style="z-index: -1; position: fixed; opacity: 1; margin-top: 8%; width:100%; height: auto;" /> | ||
− | <img class="static" src="https://static.igem.org/mediawiki/2016/f/f4/T--NUS_Singapore--Title_pic.png" alt="Background" style="z-index: 1; position: absolute; opacity: 1; margin-top: 8%;" /> | + | <img class="static" src="https://static.igem.org/mediawiki/2016/f/f4/T--NUS_Singapore--Title_pic.png" alt="Background" style="z-index: 1; position: absolute; opacity: 1; margin-top: 8%; width: 100%; height: auto;" /> |
<img class="static" src="https://static.igem.org/mediawiki/2016/8/84/T--NUS_Singapore--banner.jpg" alt="Background" style="opacity: 1; margin-top: 8%;" /> | <img class="static" src="https://static.igem.org/mediawiki/2016/8/84/T--NUS_Singapore--banner.jpg" alt="Background" style="opacity: 1; margin-top: 8%;" /> | ||
</section> | </section> | ||
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<!-- Start of Map --> | <!-- Start of Map --> | ||
<section id="canvas" class="interactive-points interactive-points--alter ha-waypoint" data-animate-down="ha-header-rotate" data-animate-up="ha-header-rotateBack" id="interactive-2" tabindex="0" style="background: rgb(22,55,72);"> | <section id="canvas" class="interactive-points interactive-points--alter ha-waypoint" data-animate-down="ha-header-rotate" data-animate-up="ha-header-rotateBack" id="interactive-2" tabindex="0" style="background: rgb(22,55,72);"> | ||
− | <img class="static" src="https://static.igem.org/mediawiki/2016/7/72/T--NUS_Singapore--Background2.png" alt="Background" style="opacity: 1; z-index: 0; width: 100%; height: 100%;" /> | + | <img class="static canvas_parts" src="https://static.igem.org/mediawiki/2016/7/72/T--NUS_Singapore--Background2.png" alt="Background" style="opacity: 1; z-index: 0; width: 100%; height: 100%;" /> |
− | <div class="CD44v6" > | + | <div class="CD44v6 canvas_parts" > |
<img id="CD44v6" class="static" src="https://static.igem.org/mediawiki/2016/5/5a/T--NUS_Singapore--CD44v6.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 1; opacity: 1;" /> | <img id="CD44v6" class="static" src="https://static.igem.org/mediawiki/2016/5/5a/T--NUS_Singapore--CD44v6.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 1; opacity: 1;" /> | ||
− | <p id="CD44v6_text" class="CD44v6_text" style="position: absolute; width: 38%; height: auto; top: | + | <p id="CD44v6_text" class="CD44v6_text" style="position: absolute; width: 38%; height: auto; top: 30%; right: 80px; text-align: justify; color: white; font-size: 1.2vw; z-index: 1; display: none;"> |
CD44 is a cell membrane protein involved in normal cell function (cell-cell and cell-matrix adhesion). However, one notable isoform, CD44v6, seems to play a major role in cancer progression, facilitating cell migration and invasion and is commonly upregulated on the surface of cancer cells. The RIOT system uses CD44v6 as a spatial marker, and recognition of this protein via a CD44v6 specific antibody allows anchoring of the engineered bacteria on the surface, triggering the expression of invasin and LLO for subsequent invasion. | CD44 is a cell membrane protein involved in normal cell function (cell-cell and cell-matrix adhesion). However, one notable isoform, CD44v6, seems to play a major role in cancer progression, facilitating cell migration and invasion and is commonly upregulated on the surface of cancer cells. The RIOT system uses CD44v6 as a spatial marker, and recognition of this protein via a CD44v6 specific antibody allows anchoring of the engineered bacteria on the surface, triggering the expression of invasin and LLO for subsequent invasion. | ||
<p> | <p> | ||
</div> | </div> | ||
− | <div class="Cancer_cell_body"> | + | <div class="Cancer_cell_body canvas_parts"> |
<img id="Cancer_cell_body" class="static" src="https://static.igem.org/mediawiki/2016/7/73/T--NUS_Singapore--Cancer_cell_body.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 2; opacity: 1;" /> | <img id="Cancer_cell_body" class="static" src="https://static.igem.org/mediawiki/2016/7/73/T--NUS_Singapore--Cancer_cell_body.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 2; opacity: 1;" /> | ||
<img id="Lactate" class="static" src="https://static.igem.org/mediawiki/2016/0/04/T--NUS_Singapore--Lactate.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 0.5; opacity: 1;" /> | <img id="Lactate" class="static" src="https://static.igem.org/mediawiki/2016/0/04/T--NUS_Singapore--Lactate.png" style="position: absolute; width: auto; height: 100%; top: 0; left: 0; z-index: 0.5; opacity: 1;" /> | ||
− | <p id="Cancer_cell_body_text" class="Cancer_cell_body_text" style="position: absolute; width: 50%; height: auto; top: 20%; right: 80px; text-align: justify; color: white; font-size: 1. | + | <p id="Cancer_cell_body_text" class="Cancer_cell_body_text" style="position: absolute; width: 50%; height: auto; top: 20%; right: 80px; text-align: justify; color: white; font-size: 1.3vw; z-index: 2; display: none;"> |
Many complex biological processes lead to all forms of cancer, and their significant hallmarks include an ability to resist cell death, prolonged signalling, the origination of angiogenesis and metastasis. Another observable trait of cancer is described by the Warburg effect where a higher rate of glycolysis increases lactic acid production. | Many complex biological processes lead to all forms of cancer, and their significant hallmarks include an ability to resist cell death, prolonged signalling, the origination of angiogenesis and metastasis. Another observable trait of cancer is described by the Warburg effect where a higher rate of glycolysis increases lactic acid production. | ||
</p> | </p> | ||
− | <p id="Cancer_cell_body_text2" class="Cancer_cell_body_text" style="position: absolute; width: 50%; height: auto; top: 45%; right: 80px; text-align: justify; color: white; font-size: 1. | + | <p id="Cancer_cell_body_text2" class="Cancer_cell_body_text" style="position: absolute; width: 50%; height: auto; top: 45%; right: 80px; text-align: justify; color: white; font-size: 1.3vw; z-index: 2; display: none;"> |
In proliferative cell types such as cancer, the bulk of the pyruvate from glycolysis is moved from the mitochondria to create lactate via lactate dehydrogenase - a process usually initiated only when oxygen supply is decreased. This production of lactate in the presence of oxygen is a direct consequence of the Warburg effect, resulting in a microenvironment with an increased lactate concentration. | In proliferative cell types such as cancer, the bulk of the pyruvate from glycolysis is moved from the mitochondria to create lactate via lactate dehydrogenase - a process usually initiated only when oxygen supply is decreased. This production of lactate in the presence of oxygen is a direct consequence of the Warburg effect, resulting in a microenvironment with an increased lactate concentration. | ||
</p> | </p> | ||
</div> | </div> | ||
− | <div class="Invasin_and_LLO"> | + | <div class="Invasin_and_LLO canvas_parts"> |
<img id="Invasin_and_LLO" class="static" src="https://static.igem.org/mediawiki/2016/0/06/T--NUS_Singapore--Invasin_and_LLO.png" style="position: absolute; width: auto; height: 100%; top: 0; right: 60%; z-index: 3; opacity: 1;" /> | <img id="Invasin_and_LLO" class="static" src="https://static.igem.org/mediawiki/2016/0/06/T--NUS_Singapore--Invasin_and_LLO.png" style="position: absolute; width: auto; height: 100%; top: 0; right: 60%; z-index: 3; opacity: 1;" /> | ||
− | <p style="position: absolute; width: 35%; height: auto; top: 25%; right: 15%; text-align: justify; color: white; font-size: 1. | + | <p style="position: absolute; width: 35%; height: auto; top: 25%; right: 15%; text-align: justify; color: white; font-size: 1.3vw; font-f z-index: 3; "> |
<span id="Invasin_and_LLO_text" class="Invasin_and_LLO_text" style="display: none;"> | <span id="Invasin_and_LLO_text" class="Invasin_and_LLO_text" style="display: none;"> | ||
Invasin is derived from the bacteria</span> | Invasin is derived from the bacteria</span> | ||
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− | <div class="Quorum_Sensing"> | + | <div class="Quorum_Sensing canvas_parts"> |
<img id="Quorum_Sensing" class="static" src="https://static.igem.org/mediawiki/2016/4/42/T--NUS_Singapore--Quorum_Sensing.png" style="position: absolute; width: auto; height: 100%; top: 0; right: 0; z-index: 4; opacity: 1;" /> | <img id="Quorum_Sensing" class="static" src="https://static.igem.org/mediawiki/2016/4/42/T--NUS_Singapore--Quorum_Sensing.png" style="position: absolute; width: auto; height: 100%; top: 0; right: 0; z-index: 4; opacity: 1;" /> | ||
− | <p id="Quorum_Sensing_text" class="Quorum_Sensing_text" style="position: absolute; width: 55%; height: auto; top: 25%; left: 180px; text-align: justify; color: white; font-size: 1. | + | <p id="Quorum_Sensing_text" class="Quorum_Sensing_text" style="position: absolute; width: 55%; height: auto; top: 25%; left: 180px; text-align: justify; color: white; font-size: 1.3vw; z-index: 4; display: none;"> |
Initially, small amounts of N-Acyl homoserine lactones (AHLs) are produced by our engineered bacteria and they freely diffuse in and out of the cell. In the tumor region where the cell density is expected to be high, the concentration of AHL also increases, and past a threshold level, LuxR binds to AHL. When this happens, the LuxR-AHL complex goes on to further activate expression of LuxI, which then produces more AHL. This results in a positive feedback loop that increases both the concentration of LuxI as well as our desired proteins, invasin and LLO. | Initially, small amounts of N-Acyl homoserine lactones (AHLs) are produced by our engineered bacteria and they freely diffuse in and out of the cell. In the tumor region where the cell density is expected to be high, the concentration of AHL also increases, and past a threshold level, LuxR binds to AHL. When this happens, the LuxR-AHL complex goes on to further activate expression of LuxI, which then produces more AHL. This results in a positive feedback loop that increases both the concentration of LuxI as well as our desired proteins, invasin and LLO. | ||
<p> | <p> | ||
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<section style="text-align: justify; color: rgb(154, 155, 155); margin-left: 7%; margin-right: 7%; margin-top: 5%; margin-bottom: 5%; font-size: 12pt;"> | <section style="text-align: justify; color: rgb(154, 155, 155); margin-left: 7%; margin-right: 7%; margin-top: 5%; margin-bottom: 5%; font-size: 12pt;"> | ||
− | <h2 style="text-align: center; color: white;"> | + | <h2 style="text-align: center; color: white;"> WELCOME TO NUS_Singapore iGEM 2016 PAGE! </h2> |
− | <p> | + | <p>Biomolecule delivery systems are often plagued by problems such as non-specific targeting and low bioavailability. We sought to design a novel system that can sense and respond to specific stimuli present in the microenvironment of pathogenic cells. We engineered a dual-sensor bacterium that can sense increased metabolite levels in its microenvironment and then respond by delivering biomolecules into target cells. As a proof-of-concept, we engineered<span style="font-style: italic;"> Escherichia coli </span>to detect increased level of lactate in biological fluid, then respond by attaching itself to a cancer cell marker, and subsequently release biomolecules into the cell. A biosafety kill switch will be activated when there is insufficient lactate present, thus minimizing non-specific targeting.</p> |
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− | <p>Our | + | <p>Our proposed system has the flexibility to be engineered to detect other metabolites by changing the gene promoter and also detect different cell types by targeting other cell receptors. In addition, the modular nature of our system also allows part of the lactate sensing mechanism to be used as a diagnostic kit, especially for detecting for elevated levels of lactate in biological fluids such as blood or serum from patients with suspected cases of sepsis or lactic acidosis. This method of detection can be carried out without any specialized equipment or impoverished areas. </p> |
</section> | </section> | ||
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<section class="content content--related"> | <section class="content content--related"> | ||
<ul class="copyright"> | <ul class="copyright"> | ||
− | <li>© NUS_Singapore iGEM 2016</li> | + | <li style="list-style: none;">© NUS_Singapore iGEM 2016</li> |
</ul> | </ul> | ||
</section> | </section> | ||
+ | <a href="#" class="go-top" style="color: white;">Go To Top</a> | ||
</div><!-- /st-pusher --> | </div><!-- /st-pusher --> | ||
</div><!-- /st-container --> | </div><!-- /st-container --> |
Latest revision as of 16:39, 19 October 2016
WELCOME TO NUS_Singapore iGEM 2016 PAGE!
Biomolecule delivery systems are often plagued by problems such as non-specific targeting and low bioavailability. We sought to design a novel system that can sense and respond to specific stimuli present in the microenvironment of pathogenic cells. We engineered a dual-sensor bacterium that can sense increased metabolite levels in its microenvironment and then respond by delivering biomolecules into target cells. As a proof-of-concept, we engineered Escherichia coli to detect increased level of lactate in biological fluid, then respond by attaching itself to a cancer cell marker, and subsequently release biomolecules into the cell. A biosafety kill switch will be activated when there is insufficient lactate present, thus minimizing non-specific targeting.
Our proposed system has the flexibility to be engineered to detect other metabolites by changing the gene promoter and also detect different cell types by targeting other cell receptors. In addition, the modular nature of our system also allows part of the lactate sensing mechanism to be used as a diagnostic kit, especially for detecting for elevated levels of lactate in biological fluids such as blood or serum from patients with suspected cases of sepsis or lactic acidosis. This method of detection can be carried out without any specialized equipment or impoverished areas.