Difference between revisions of "Team:AshesiGhana/Description"

Line 15: Line 15:
 
</head>
 
</head>
  
 +
<body>
 +
<div class="bg-primary">
 +
<section class="bg-primary">
 +
<div class="col-lg-16 col-centered" >
 +
<center>
 +
    <specialh2 style="text-transform: lowercase;">Project Description</specialh2> <br><br><br><br><br><br>
 +
  </center> 
  
−
<div class="column full_size">
+
</div>
−
<h1>Description</h1>
+
<div class="container">
 +
<div class="col-lg-12 text-justify col-centered bg-primary">
 +
<center>
 +
<specialh3>Why are Co-cultures useful?</specialh3>
 +
<hr class="blue">
 +
</center>
 +
<div class="col-lg-8 text-justify">
 +
<p>In nature, microorganisms do not exist in isolation but interact and cooperate in complex ecosystems, a phenomenon which synthetic biological systems have yet to fully harness. Technologies that enable the engineering of synthetic ecosystems, or co-cultures, are crucial not only for the study of these natural systems but also for the advancement of synthetic biology.  Developments that enable this foundational leap  in how we engineer biology will allow the creation of synthetic populations that grow together and work together, unlocking the full potential of multicellular engineering in synthetic biology. From creating antibiotic-free human therapeutics and chemical-free biofertilizer based on microbiome engineering, to reprogrammable and dynamic biomaterials, engineering cooperation into synthetic ecosystems and co-cultures has the potential to change how we use biology forever.</p>
 +
</div>
 +
<div class="col-lg-4 text-justify">
 +
<img src="https://static.igem.org/mediawiki/2016/0/0e/T--Imperial_College--Cell_community.png" />
 +
</div>
 +
</div>
 +
</div>
 +
</section>
  
−
<p>Tell us about your project, describe what moves you and why this is something important for your team.</p>
+
<div class="container">
 +
<div class="col-lg-16 text-justify col-centered bg-primary">
 +
<center>
 +
<specialh3> Applications of Co-cultures</specialh3>
 +
<hr class="blue">
 +
</center>
 +
<div class="col-lg-18 col-centered">
 +
<p>
 +
<button class="btn-link" data-balloon-length="large" data-balloon="One of our favorite application was the idea of modelling financial systems using microbial communities. We came across the following papers. We researched and determined that natural systems’ adaptation processes might reveal methods for streamlining bank interconnections and maintaining diversity in order to protect against global financial crisis. We thought that we could simulate “big bank” and “small bank” populations thanks to our G.E.A.R. population control system. This artificial consortia could then be used to study how the damage on one population (or node) is propagated through the system, and therefore study how the system’s robustness varies as a function of diversity." data-balloon-pos="up">
 +
<a class="foo" href="#Financial" >
 +
        <img src="https://static.igem.org/mediawiki/2016/b/b6/T--Imperial_College--financial_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/c/cd/T--Imperial_College--financials_back.png" height="190" />
 +
    </a>
 +
  </button>
  
 +
<button class="btn-link" data-balloon-length="large" data-balloon=" Our body is inhabited by about 100 trillions micro-organisms(2) , they form what is called our human microbiome and it has been shown that they have huge implications on our health. For example Clostridium difficile is responsible for the death of approximately 29,000 death in the US per year(3)  C. difficile is an opportunistic bacteria that colonise your gut microbiome when it is in dysbiosis. Hence we thought that we could use our system to monitor and modulate the proportion of microbiome species and determine whether they are at the healthy ratio or not. If not our system would produce a response to restore healthy ratio through drug production, or growth regulation, etc." data-balloon-pos="up"> 
 +
<a class="foo" href="#Health">
 +
<img src="https://static.igem.org/mediawiki/2016/4/45/T--Imperial_College--health_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/7/73/T--Imperial_College--health_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
 
 +
<button class="btn-link" data-balloon-length="large" data-balloon=" This idea emerged from one of our visit to the Royal College of Art final project presentations. We wanted to design a novel material with exciting properties, so we imagined a novel material which would be light-moldable. The material would be generated by two populations of positive and negative phototaxis cells. These two populations would produce an adhesive protein, which would allow the cells to aggregate. By stipulating the ratio of the negative and positive phototaxis cells we could control the thickness of the material. The different properties of the populations could be exploited to create customisable household items." data-balloon-pos="up">
 +
  <a class="foo" href="#Staple">
 +
      <img src="https://static.igem.org/mediawiki/2016/f/f3/T--Imperial_College--consume_stable_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/1/10/T--Imperial_College--consume_staple_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
 
 +
  <button class="btn-link" data-balloon-length="large" data-balloon=" After reading the Weber paper Synthetic ecosystems based on airborne inter- and intrakingdom communication(1) we thought about using our circuit to create an artificial healthy microbiome on spacecrafts. This would be possible as the papers shows that microbes can communicate through an airborne system. The symbiotic microbes will prevent pathogenic bacteria from overtaking the spacecraft. And therefore our system would keep the astronauts and space travellers happy and healthy on their flights to outer space." data-balloon-pos="up"> 
 +
<a class="foo" href="#Indu">
 +
        <img src="https://static.igem.org/mediawiki/2016/d/d3/T--Imperial_College--industries_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/8/84/T--Imperial_College--industries_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
 
 +
  <button class="btn-link" data-balloon-length="large" data-balloon=" We imagined a technology which would provide a more sustainable way of consuming/producing probiotics. The user would buy a vial of pre-mixed cells equipped with our Genetically Engineered Artificial Ratio (G.E.A.R.) system. The user would then grow the purchased cells in his or her mini bioreactor, just like growing herbs and spices in your backyard. The G.E.A.R. system would control the cells ratio, allowing the production of probiotics of a desired composition." data-balloon-pos="up">
 +
<a class="foo" href="#Dis">
 +
        <img src="https://static.igem.org/mediawiki/2016/5/5b/T--Imperial_College--consumer_dis_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/3/33/T--Imperial_College--consumer_discrete_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
<br>
  
−
<h5>What should this page contain?</h5>
+
<button class="btn-link" data-balloon-length="large" data-balloon=" Consortia of bacteria with the ability to degrade cellulose and xylose allow more efficient production of biofuels. By separating the task of cellulose degradation and biofuel production between different cells we can increase the yield of biofuel." data-balloon-pos="up">  
−
<ul>
+
<a class="foo" href="#Energy">
−
<li> A clear and concise description of your project.</li>
+
        <img src="https://static.igem.org/mediawiki/2016/b/b3/T--Imperial_College--energy_front.png" height="190"/>
−
<li>A detailed explanation of why your team chose to work on this particular project.</li>
+
        <img src="https://static.igem.org/mediawiki/2016/c/c5/T--Imperial_College--energy_back.png" height="190" />
−
<li>References and sources to document your research.</li>
+
    </a>
−
<li>Use illustrations and other visual resources to explain your project.</li>
+
  </button>
−
</ul>
+
 
 +
  <button class="btn-link" data-balloon-length="large" data-balloon="Natural materials, like skin, have intricate material and structural properties which are hard to mimic in artificial materials. We could use microbes as biological 3D printers that can manufacture materials that these unique properties. Using our microbial consortia, we could 3D print composite materials at a microscopic level. Different material properties can be controlled by different ratios of the consortia population." data-balloon-pos="up">
 +
   
 +
<a class="foo" href="#Materials">
 +
        <img src="https://static.igem.org/mediawiki/2016/1/19/T--Imperial_College--materials_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/b/b4/T--Imperial_College--materials_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
 
 +
  <button class="btn-link" data-balloon-length="large" data-balloon="Microbial fuel cells can treat wastewater and simultaneously generate energy.  We can use consortia of Geobacter sulfurreducens and E. coli for a more efficient microbial fuel cell.  G. sulfurreducens work best in anaerobic conditions.  E. coli scavenge oxygen which is toxic to G. sulfurreducens enabling MFC operation in aerobic conditions.  However, production of succinate by E. coli reduced the efficiency of the fuel cell.  We can control the ratio of E. coli and G. sulfurreducens to optimise oxygen scavenging and maximising energy production while minimising succinate production" data-balloon-pos="up">
 +
 
 +
<a class="foo" href="#Utility">
 +
        <img src="https://static.igem.org/mediawiki/2016/d/d3/T--Imperial_College--utilities_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/c/c3/T--Imperial_College--utilities_back.png" height="190" />
 +
    </a>
 +
  </button>
 +
 +
  <button class="btn-link" data-balloon-length="large" data-balloon="Nano-devices are being developed as a diagnostic and therapeutic tool.  There is a need for nanoscale transmission systems for these devices to exchange information amongst themselves. Use bacteria as communication system by transferring information with DNA.  Bacteria travel from node to node through chemotaxis. Population control could be used to prevent bacteria carrying the same message from overloading the node. In network theory, our bacteria act like edges and by tuning the ratio you could tune the strength of these edges. We could get a sophisticated communication network between nano-devices." data-balloon-pos="up">
  
 +
<a class="foo" href="#Tele">
 +
        <img src="https://static.igem.org/mediawiki/2016/9/9e/T--Imperial_College--telecom_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/e/e3/T--Imperial_College--telecom_back.png" height="190" />
 +
  </a>
 +
</button>
  
 +
  <button class="btn-link" data-balloon-length="large" data-balloon="Conductive biomaterial with controllable electronic properties for applications in biocompatible, low-cost electronics.  Pilin nanofilaments (pili) — also known as microbial nanowires — are a class of fibrous proteins that are found in sediment bacteria. Biofilms made of pili taken from G. sulfurreducens exhibit electrical conductivity. By modulating the ratio of the G. sulfurreducens and other species you can modify the electrical properties of the biofilms." data-balloon-pos="up"> 
 +
 
 +
<a class="foo" href="#InfoTech">
 +
        <img src="https://static.igem.org/mediawiki/2016/c/c2/T--Imperial_College--infotech_front.png" height="190"/>
 +
        <img src="https://static.igem.org/mediawiki/2016/9/9a/T--Imperial_College--infotech_back.png" height="190" />
 +
  </a>
 +
</button>
 +
 +
</p>
 +
 +
 +
</div>
 +
</div>
 
</div>
 
</div>
 +
</section>
  
−
<div class="column full_size" >
 
  
−
<h5>Advice on writing your Project Description</h5>
 
  
−
<p>
+
<section class="bg-primary">
−
We encourage you to put up a lot of information and content on your wiki, but we also encourage you to include summaries as much as possible. If you think of the sections in your project description as the sections in a publication, you should try to be consist, accurate and unambiguous in your achievements.
+
<div class="container">
−
</p>
+
<div class="col-lg-12 text-justify col-centered bg-primary">
  
−
<p>
+
<center>
−
Judges like to read your wiki and know exactly what you have achieved. This is how you should think about these sections; from the point of view of the judge evaluating you at the end of the year.
+
<specialh3>Why aren’t we using co-cultures yet?</specialh3>
 +
<hr class="blue">
 +
</center>
 +
<div class="col-lg-4 text-justify">
 +
<img src="https://static.igem.org/mediawiki/2016/4/47/T--Imperial_College--Cell_outcompete.png" />
 +
</div>
 +
<div class="col-lg-8 text-justify">
 +
<p>To determine why more labs aren’t using co-cultures, we visited Imperial College London's Centre for Synthetic Biology. We found that many researchers find it too difficult to determine conditions under which multiple cell types would survive. Different cell types grow best at different conditions and there are few established protocols that tell you exactly how you should grow them together. If conditions are not carefully balanced, one cell type tends to out-compete the other. Currently, this problem is addressed by various population control methods, such as auxotrophic cross-feeding and toxin-antitoxin systems. However, these techniques are neither robust, nor portable across different organisms, nor  do they allow precise ratiometric control of the different populations of cells.
 
</p>
 
</p>
 +
</div>
 +
  
 
</div>
 
</div>
  
 +
</div>
  
−
<div class="column half_size" >
 
  
−
<h5>References</h5>
+
</section>
−
<p>iGEM teams are encouraged to record references you use during the course of your research. They should be posted somewhere on your wiki so that judges and other visitors can see how you thought about your project and what works inspired you.</p>
+
  
−
</div>
 
  
 +
<section class="bg-primary">
 +
<div class="container">
  
−
<div class="column half_size" >
+
<center>
−
<h5>Inspiration</h5>
+
<specialh3>What are we doing?</specialh3>
−
<p>See how other teams have described and presented their projects: </p>
+
<hr class="blue">
 +
</center>
 +
<div class="col-lg-12 col-centered text-justify">
 +
<p>We have set out to engineer a genetic circuit that allows ratiometric control of populations in a co-culture to allow future synthetic biologists to realise the full potential of synthetic ecosystems. <br><br>
  
−
<ul>
+
Our genetic circuit employs three modules. The first is the communication module, which utilises two orthogonal quorum sensing systems to allow our <i>E. coli</i> populations to detect their own population density, as well as that of the other population. <br><br>
−
<li><a href="https://2016.igem.org/Team:Imperial_College/Description">2016 Imperial College</a></li>
+
 
−
<li><a href="https://2016.igem.org/Team:Wageningen_UR/Description">2016 Wageningen UR</a></li>
+
In order to allow for different quorum sensing systems to be utilised in the circuit, we chose to work with four possible systems: Las, Rhl, Lux, and Cin. The Las, Rhl, and Lux transcriptional activators, LasR, RhlR, and LuxR, are fairly well characterised in the Biobrick registry. However, the Cin transcriptional activator is not. <br><br>As a result, crosstalk characterisation for LasR, RhlR, and LuxR did not include Cin 3O-C14 AHL. Therefore, to improve the characterisation of these parts, we performed cross talk experiments with Cin 3O-C14 AHL. Additionally, while a part for CinR does exist in the registry, it has an LVA tag and is uncharacterised. We made a new part for CinR without an LVA tag, and are working to characterise it, and perform crosstalk experiments for CinR with the AHLs associated with Las, Rhl, and Lux. <br><br></p>
−
<li><a href="https://2014.igem.org/Team:UC_Davis/Project_Overview"> 2014 UC Davis</a></li>
+
<center>
−
<li><a href="https://2014.igem.org/Team:SYSU-Software/Overview">2014 SYSU Software</a></li>
+
<img src="https://static.igem.org/mediawiki/2016/d/d3/T--Imperial_College--quorumSensing.png" height="200"/><br><br>
−
</ul>
+
</center>
 +
<p>Our second module, the comparator module, links quorum sensing signals to RNA logic so that the bacteria can compare their own population to the population of the other cell line.<br><br>
 +
<center>
 +
<img src="https://static.igem.org/mediawiki/2016/a/a3/T--Imperial_College--RNA_balance.png" height=200/><br><br>
 +
</center><p>
 +
The final module is a growth regulation module which allows our cell lines to respond to the signal relayed by the comparator module. If its population is too large, a growth inhibiting protein is expressed, allowing the population ratios to balance once again. <br><br></p>
 +
<center>
 +
<img src="https://static.igem.org/mediawiki/2016/5/5c/T--Imperial_College--NoDivide.png" height=200/><br><br>
 +
</center><p>
 +
In addition to the circuit, we have produced a software tool, A.L.I.C.E, which helps scientists design their own co-culture experiments. We have worked with other iGEM teams to generate the preliminary data for A.L.I.C.E. Our project aims to provide a framework to advance the use of co-cultures in synthetic biology and in research of microbial consortia.
 +
 
 +
</p>
 
</div>
 
</div>
 +
</div>
 +
 +
<div class="text-center">
 +
<div class="some-padding"></div>
 +
 +
<figure>
 +
<img src="https://static.igem.org/mediawiki/2016/3/31/T--Imperial_College--full_circuit.png" height="400">
 +
<figcaption><p>This is a diagram of our full circuit, with all three modules.</p></figcaption>
 +
</figure>
 +
</div>
 +
 +
</section>
 +
  
  
 +
</body>
  
 
</html>
 
</html>

Revision as of 10:06, 13 July 2017

Project Description





Why are Co-cultures useful?

In nature, microorganisms do not exist in isolation but interact and cooperate in complex ecosystems, a phenomenon which synthetic biological systems have yet to fully harness. Technologies that enable the engineering of synthetic ecosystems, or co-cultures, are crucial not only for the study of these natural systems but also for the advancement of synthetic biology. Developments that enable this foundational leap in how we engineer biology will allow the creation of synthetic populations that grow together and work together, unlocking the full potential of multicellular engineering in synthetic biology. From creating antibiotic-free human therapeutics and chemical-free biofertilizer based on microbiome engineering, to reprogrammable and dynamic biomaterials, engineering cooperation into synthetic ecosystems and co-cultures has the potential to change how we use biology forever.

Applications of Co-cultures


Why aren’t we using co-cultures yet?

To determine why more labs aren’t using co-cultures, we visited Imperial College London's Centre for Synthetic Biology. We found that many researchers find it too difficult to determine conditions under which multiple cell types would survive. Different cell types grow best at different conditions and there are few established protocols that tell you exactly how you should grow them together. If conditions are not carefully balanced, one cell type tends to out-compete the other. Currently, this problem is addressed by various population control methods, such as auxotrophic cross-feeding and toxin-antitoxin systems. However, these techniques are neither robust, nor portable across different organisms, nor do they allow precise ratiometric control of the different populations of cells.

What are we doing?

We have set out to engineer a genetic circuit that allows ratiometric control of populations in a co-culture to allow future synthetic biologists to realise the full potential of synthetic ecosystems.

Our genetic circuit employs three modules. The first is the communication module, which utilises two orthogonal quorum sensing systems to allow our E. coli populations to detect their own population density, as well as that of the other population.

In order to allow for different quorum sensing systems to be utilised in the circuit, we chose to work with four possible systems: Las, Rhl, Lux, and Cin. The Las, Rhl, and Lux transcriptional activators, LasR, RhlR, and LuxR, are fairly well characterised in the Biobrick registry. However, the Cin transcriptional activator is not.

As a result, crosstalk characterisation for LasR, RhlR, and LuxR did not include Cin 3O-C14 AHL. Therefore, to improve the characterisation of these parts, we performed cross talk experiments with Cin 3O-C14 AHL. Additionally, while a part for CinR does exist in the registry, it has an LVA tag and is uncharacterised. We made a new part for CinR without an LVA tag, and are working to characterise it, and perform crosstalk experiments for CinR with the AHLs associated with Las, Rhl, and Lux.



Our second module, the comparator module, links quorum sensing signals to RNA logic so that the bacteria can compare their own population to the population of the other cell line.



The final module is a growth regulation module which allows our cell lines to respond to the signal relayed by the comparator module. If its population is too large, a growth inhibiting protein is expressed, allowing the population ratios to balance once again.



In addition to the circuit, we have produced a software tool, A.L.I.C.E, which helps scientists design their own co-culture experiments. We have worked with other iGEM teams to generate the preliminary data for A.L.I.C.E. Our project aims to provide a framework to advance the use of co-cultures in synthetic biology and in research of microbial consortia.

This is a diagram of our full circuit, with all three modules.