Difference between revisions of "Team:Cardiff Wales"

 
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<br><br><br><img id="rcorners2" src="https://static.igem.org/mediawiki/2017/thumb/8/83/T--Cardiff_Wales--Title1.png/800px-T--Cardiff_Wales--Title1.png"/><br><br><br>
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<img id="rcorners1" src="https://static.igem.org/mediawiki/2017/thumb/a/a5/T--Cardiff_Wales--iGEMCardiffLogo.png/600px-T--Cardiff_Wales--iGEMCardiffLogo.png">
  
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<p> <br><h2> <b>Nominated for the 'Best Therapeutic Project' award at the iGEM Giant Jamboree</b></h2><br> </p>
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<h1> Using Plant Synthetic Biology to generate therapeutics for treatment of thyroid disease. </h1>
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<p><b>The 2017 Cardiff-Wales project has dual aims.</b></p>
 
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Primarily we will develop tools for plant synthetic biology using the golden gate phytobricks standard. We will take previously characterized promotor elements that respond to a variety of environmental stimuli and move these into the phytobrick standard. These promotor elements will be used to generate TUs that drive reporter gene expression and will represent useful tools for future iGEM teams. </p>
 
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Secondly we will use these phytobricks to express the composite TSHantag protein, which is an antagonist for Graves Disease, caused by hyperthyroidism. The TSHantag has not previously been used as a therapeutic agent so we will use the tobacco gene expression system to produce high levels of the protein, which will then be tested in a human <i>in vitro</i> system by collaborators at the Cardiff University Medical School.</p>
 
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We have expertise using the tobacco expression system so will welcome collaborations with iGEM teams who wish to test the function of their proteins in plants! </p>
 
  
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<p><b>This promises to be an exciting year of iGEM research!
 
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<p  align="left" style="background-color:#ffffff"> <br><br> The <b> Cardiff Wales 2017 iGEM team</b> had two main goals:</br><br>> To develop new tools in the <a href="https://2016.igem.org/Resources/Plant_Synthetic_Biology/PhytoBricks">Phytobrick</a> standard that can be used for future studies using plant gene expression. </br><br>> To use the <i> Nicotiana benthamiana </i> leaf expression system to generate high levels of a protein that might be used as a therapeutic for <a href="https://en.wikipedia.org/wiki/Graves'_disease">Graves' disease,</a>which is a major human autoimmune disease affecting thyroid function. </br>
  
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<br> The Phytobrick standard uses the golden gate cloning system so we incorporated a set of previously-characterised plant promotors into this cloning system. Our promoters are designed to respond to several different hormone or environmental stimuli and are taken from the model plant <i> Arabidopsis thaliana</i>. <br><br> In order to test the function of these promotors we aimed to quantify their expression levels using luciferase transcriptional units and also use them to generate a thyroid stimulating hormone antagonist that might have the potential to treat Graves' disease.</br> <br>Consequently, we have added <a href="https://2017.igem.org/Team:Cardiff_Wales/basicparts">several parts</a> to the phytobrick registry. In addition we generated a <a href="http://parts.igem.org/Part:BBa_K2404013">Phytobrick level 1 construct</a> that includes a luciferase gene that in future will provide a method that allows iGEM teams to simply evaluate whether their tobacco leaf transformations have been successful.<br> <br>More details about the project can be found on our <a href="https://2017.igem.org/Team:Cardiff_Wales/projectdescription">project description page</a>.
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We also developed a <a href="https://2017.igem.org/Team:Cardiff_Wales/Modelling">model</a> that is designed to be flexible so that it can be used as a tool for future iGEM teams or even companies. This was designed so that it can estimate how many plants are needed to create a single dose of any plant-produced therapeutic with a given severity, depending on the plant expression system of choice. For our project, we used this model to estimate how many plants might be required to provide a single effective dose of our TSH antagonist. We demonstrated the flexibility by changing one variable extensively, so that it shows different expression vectors and systems.</br> <br>We then integrated the <a href="https://2017.igem.org/Team:Cardiff_Wales/Our_research">research</a> section of our <a href="https://2017.igem.org/Team:Cardiff_Wales/Human_Practices">human practices</a> with the model, in order to estimate how many plants would be required using each expression platform to give a single effective dose to every sufferer of Graves' disease in the USA.
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<h5>Before you start: </h5>
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<p> Please read the following pages:</p>
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<li> <a href="https://2017.igem.org/Competition">Competition Hub</a> </li>
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<li> <a href="https://2017.igem.org/Competition/Deliverables/Wiki">Wiki Requirements page</a></li>
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<li> <a href="https://2017.igem.org/Resources/Template_Documentation">Template documentation</a></li>
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<h5> Styling your wiki </h5>
 
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<p>You may style this page as you like or you can simply leave the style as it is. You can easily keep the styling and edit the content of these default wiki pages with your project information and completely fulfill the requirement to document your project.</p>
 
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<p>While you may not win Best Wiki with this styling, your team is still eligible for all other awards. This default wiki meets the requirements, it improves navigability and ease of use for visitors, and you should not feel it is necessary to style beyond what has been provided.</p>
 
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<h5> Wiki template information </h5>
 
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<p>We have created these wiki template pages to help you get started and to help you think about how your team will be evaluated. You can find a list of all the pages tied to awards here at the <a href="https://2017.igem.org/Judging/Pages_for_Awards">Pages for awards</a> link. You must edit these pages to be evaluated for medals and awards, but ultimately the design, layout, style and all other elements of your team wiki is up to you!</p>
 
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<h5> Editing your wiki </h5>
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<p>On this page you can document your project, introduce your team members, document your progress and share your iGEM experience with the rest of the world! </p>  
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<p> <a href="https://2017.igem.org/wiki/index.php?title=Team:Example&action=edit"> </a>Use WikiTools - Edit in the black menu bar to edit this page</p>
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<h2><center> Graves' Disease </center> </h2>
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<p>This wiki will be your team’s first interaction with the rest of the world, so here are a few tips to help you get started: </p>
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<li>Avoid using very small fonts and low contrast colors; information should be easy to read.  </li>
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<li>Start documenting your project as early as possible; don’t leave anything to the last minute before the Wiki Freeze. For a complete list of deadlines visit the <a href="https://2017.igem.org/Calendar">iGEM 2017 calendar</a> </li>
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Grave’s Disease arises from the overproduction of the thyroid stimulating hormone (TSH). </br><br>Such overproduction leads to increased thyroxine levels, consequently resulting in hyperthyroidism. Our project will involve the expression of the human thyroid stimulating hormone antagonist (TSHantag) using the tobacco leaf expression system. </br><br>As of yet, there have been no examples using the tobacco system for expression of the TSHantag protein. Therefore, we will design and create unique transcriptional units (TUs) for expression of TSHantag in tobacco. These TUs will be introduced into tobacco using agrobacterium-mediated transformation. </br><br> At the end of the project our attempts to optimise the amount of TSH protein produced in tobacco are still ongoing. However we have already arranged a collaboration with thyroid researchers at <a href=https://www.cardiff.ac.uk/people/view/78690-dayan-colin">University Hospital of Wales.</a>They will test the efficacy of the plant-produced TSHantag in an <i>in vitro</i> diagnostic system. <br><br><br></p>
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<p> You can also view other team wikis for inspiration! Here are some examples:</p>
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<li> <a href="https://2014.igem.org/Team:SDU-Denmark/"> 2014 SDU Denmark </a> </li>
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<li> <a href="https://2014.igem.org/Team:Aalto-Helsinki">2014 Aalto-Helsinki</a> </li>
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<li> <a href="https://2014.igem.org/Team:LMU-Munich">2014 LMU-Munich</a> </li>
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<li> <a href="https://2014.igem.org/Team:Michigan"> 2014 Michigan</a></li>
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<li> <a href="https://2014.igem.org/Team:SCU-China"> 2014 SCU-China </a></li>
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<h5> Uploading pictures and files </h5>
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Latest revision as of 18:05, 5 December 2017








Nominated for the 'Best Therapeutic Project' award at the iGEM Giant Jamboree






The Cardiff Wales 2017 iGEM team had two main goals:

> To develop new tools in the Phytobrick standard that can be used for future studies using plant gene expression.

> To use the Nicotiana benthamiana leaf expression system to generate high levels of a protein that might be used as a therapeutic for Graves' disease,which is a major human autoimmune disease affecting thyroid function.

The Phytobrick standard uses the golden gate cloning system so we incorporated a set of previously-characterised plant promotors into this cloning system. Our promoters are designed to respond to several different hormone or environmental stimuli and are taken from the model plant Arabidopsis thaliana.

In order to test the function of these promotors we aimed to quantify their expression levels using luciferase transcriptional units and also use them to generate a thyroid stimulating hormone antagonist that might have the potential to treat Graves' disease.

Consequently, we have added several parts to the phytobrick registry. In addition we generated a Phytobrick level 1 construct that includes a luciferase gene that in future will provide a method that allows iGEM teams to simply evaluate whether their tobacco leaf transformations have been successful.

More details about the project can be found on our project description page.

We also developed a model that is designed to be flexible so that it can be used as a tool for future iGEM teams or even companies. This was designed so that it can estimate how many plants are needed to create a single dose of any plant-produced therapeutic with a given severity, depending on the plant expression system of choice. For our project, we used this model to estimate how many plants might be required to provide a single effective dose of our TSH antagonist. We demonstrated the flexibility by changing one variable extensively, so that it shows different expression vectors and systems.

We then integrated the research section of our human practices with the model, in order to estimate how many plants would be required using each expression platform to give a single effective dose to every sufferer of Graves' disease in the USA.




Graves' Disease



Grave’s Disease arises from the overproduction of the thyroid stimulating hormone (TSH).

Such overproduction leads to increased thyroxine levels, consequently resulting in hyperthyroidism. Our project will involve the expression of the human thyroid stimulating hormone antagonist (TSHantag) using the tobacco leaf expression system.

As of yet, there have been no examples using the tobacco system for expression of the TSHantag protein. Therefore, we will design and create unique transcriptional units (TUs) for expression of TSHantag in tobacco. These TUs will be introduced into tobacco using agrobacterium-mediated transformation.

At the end of the project our attempts to optimise the amount of TSH protein produced in tobacco are still ongoing. However we have already arranged a collaboration with thyroid researchers at University Hospital of Wales.They will test the efficacy of the plant-produced TSHantag in an in vitro diagnostic system.