Difference between revisions of "Team:Duke"

 
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<h2> Welcome to iGEM 2016! </h2>
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<p>We are Team Duke! </p>
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      <center><img style="margin: 0 auto"src="https://static.igem.org/mediawiki/2016/0/06/T--Duke--TeamPic.jpeg" alt="Team" width="900" height="850"></center>
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      <h2>Hello! We’re the Duke iGEM!</h2>
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      <p>We are group of undergrads that came together because we are really passionate about synthetic biology. We spent our summer working on synthesizing Taxol. We learned a lot about bioengineering and had fun doing it.</p>
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<h2>Our Project</h2>
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      <center><img src="https://static.igem.org/mediawiki/2016/8/87/T--Duke--Yew_Berries.jpg" alt="Yew Berries" width="1050" height="850"></center>
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<h3 style="text-align:center;">Biosynthesis of Taxol in <i>E.coli</i></h3>
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<h4>What is Taxol? Why is it important?</h4>
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      <h2>CANCER MEDICINE PLANT IN SHORT SUPPLY</h2>
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      <p>The main Taxol plant (Taxus Bervifolia) is few in number <br /> Duke iGEM engineers and grows bacteria through humane methods to provide infinite supplies of taxol to treat cancer</p>
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Taxol, generically known as paclitaxel, is a chemotherapy drug highly efficient in combating multiple forms of cancer via interference with the normal breakdown of microtubules during cell division. Taxol’s efficacy has earned it a place on the World Health Organization’s Model List of Essential Medicines, a roster of the most critical medications needed for a basic health system.
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<section class="bg-primary" id="about" style="background-image: url(https://static.igem.org/mediawiki/2016/c/c3/T--Duke--Canada_and_.jpeg); background-size: cover; background-position: center">
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                    <h1 class="section-heading" style="font-family: Indie Flower; font-weight:bolder; font-size: 55px">How to Produce Lots of <br/>Cancer Drugs Sustainably?</h1>
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                <p class="text-right" style="color: black;font-family: Indie Flower; Comic Sans MS; font-size: 30px;">Presented by Duke iGEM <img src="https://static.igem.org/mediawiki/2016/c/c4/T--Duke--logo_and_.jpeg" width="10%"></p>
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<figcaption border= "1px dotted blue" text-align= "center"> Fig1. - Rotating Paclitaxel Molecule Model.</figcaption>
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<h4>Serious Issues with Taxol Production</h4>
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Not surprisingly, there is an ever-increasing demand for taxol. Unfortunately, current production methods for the drug do not provide a long-term, sustainable supply. Taxol is derived from the bark of the Pacific yew tree, <i>Taxus brevifolia</i>, but isolation from its natural source is hindered by the slow growth of the tree and by the low concentration of the drug in the bark. Consequentially, large numbers of yew trees must be harvested for modest returns. Other production methods make use of chemical and semi-chemical synthesis, but the intricate stereoisomerism and multistep pathway of taxol production result in low yield rates and high production costs. Deriving taxol from nature is environmentally unsustainable; chemically synthesizing it is economically unsustainable.  
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Biosynthesis of taxol is the best solution to the shortcomings of the aforementioned production methods. Plant cell fermentation has been shown to synthesize taxol somewhat effectively and requires minimal harvesting of the yew tree. As impressive as plant cell fermentation is, the potential for taxol synthesis in bacteria, an organism much simpler and far more optimized for fermentation, is vastly greater. Duke iGEM’s goal is to optimize the biosynthesis of taxol in <i>E.coli</i>.  
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<h2 style="color:#337ab7; font-family: Muli; font-size: 3em"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span> Identifying Cancer Drug in Short Supply</h2>
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<p>Our case is taxol, a famous chemotherapy drug that derives its chemistry from Pacific Yew Tree barks.</p>
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<h4 style="font-family:Raleway; display:block; margin-right:1em;text-align:center">Annotated Taxol 2D Structure <span class="text-muted">(3D Structure in Project Page)</span></h4>
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<h6>PDB Citation: Bank, RCSB Protein Data. "TAXOL." RCSB PDB. N.p., n.d. Web. 27 Sept. 2016.</h6>
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      <p style="font-family: Raleway; font-size:20px">The lack of chemotherapy drugs risks patients' lives. Taxol is a famous and effective cancer drug whose production rests on the steady supply of Pacific Yew Trees. However, as more people develop cancer, Pacific Yew Trees are being overharvested and endangered.</p>
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  <p style="font-family: Raleway; font-size:20px">In the forseeable future, there will be fewer Yew Trees. Taxol will become less affordable for patients. Worse, when Yew Trees become extinct, Taxol will lose its most essential ingredient. What can we do?</p>
  
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<h4>Our Solution</h4>
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Our primary objective is to individually characterize and then consolidate known enzymes of the taxol biosynthesis pathway into a single strain of <i>E.coli</i>. As such, our research plan consists primarily of two components: a cloning project and kinetic assays to characterize the system. Additionally, the existing enzymes as found in published literature may be insufficient for highly effective production of taxol. In their current states, the enzymes have a wide range of turnover rates that would lead to bottlenecks in the pathway even with high expression. Optimization projects targeting the enzymes with the lowest turnover rates will be undertaken to remedy the bottlenecks.
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Currently, we have successfully cloned the majority of our enzymes into <i>E.coli</i> using Gibson assembly and are in the early stages of kinetic assays, most of which take advantage of CoA chemistry. Once cloning and assays are complete, we will combine the enzymes into one plasmid via Golden Gate assembly.  
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      <p style="font-family: Raleway; font-size:20px">After an analysis of Yew Trees' genetic structure relevant to taxol production, we identified eight transferrable essential genetic sequences for producing taxol ingredients.</p>
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<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; More efficient synthesis of taxol will lower the cost of the drug and its production, but this cost is not the only determining factor of accessibility. In order to understand how lowering the cost of drug production will translate into more available treatment, members of Duke iGEM with experience in bioethics, pharmaceutical patent law, and economics are analyzing and modeling the actual cost of taxol treatment by taking into account healthcare systems and distribution logistics.
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  <p style="font-family: Raleway; font-size:20px">Therefore, it's possible to reinvent taxol production. The next important step is to find the perfect replacement producer to relieve the Yew Trees of their noble duty.</p>
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<h2 style="color:#337ab7;font-family: Muli; font-size:3em" ><span class="glyphicon glyphicon-search" aria-hidden="true"></span> Rethink the Production Process</h2>
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<p>New producer will dramatically increase taxol production, allow Pacific Yew Trees a permanent break from overharvest and danger of extinction. </p>
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<h2 style="color:#337ab7;font-family: Muli;font-size:3em"><i class="fa fa-check-square-o" aria-hidden="true"></i></span> Bacteria!</h2>
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<p>Bacterial Production in a controlled lab is safe and sustainable, with a dramatically larger yield!</p>
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      <p style="font-family: Raleway; font-size:20px">At Duke iGEM, we have already begun the process of sequentially arranging these genes and growing bacteria with these new powers. </p>
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  <p style="font-family: Raleway; font-size:20px">We believe our idea is implementable and has a revolutionary positive impact on future treatments of cancer, saving more lives at a lower cost.</p>
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        <p class="text-muted" style="font-size:20px;font-family: Raleway;text-align:center">@ 2016 Duke University iGEM</p>
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Latest revision as of 20:26, 19 October 2016

How to Produce Lots of
Cancer Drugs Sustainably?

Presented by Duke iGEM

Identifying Cancer Drug in Short Supply

Our case is taxol, a famous chemotherapy drug that derives its chemistry from Pacific Yew Tree barks.

Error: Embedded data could not be displayed.

Annotated Taxol 2D Structure (3D Structure in Project Page)

PDB Citation: Bank, RCSB Protein Data. "TAXOL." RCSB PDB. N.p., n.d. Web. 27 Sept. 2016.

The lack of chemotherapy drugs risks patients' lives. Taxol is a famous and effective cancer drug whose production rests on the steady supply of Pacific Yew Trees. However, as more people develop cancer, Pacific Yew Trees are being overharvested and endangered.

In the forseeable future, there will be fewer Yew Trees. Taxol will become less affordable for patients. Worse, when Yew Trees become extinct, Taxol will lose its most essential ingredient. What can we do?

After an analysis of Yew Trees' genetic structure relevant to taxol production, we identified eight transferrable essential genetic sequences for producing taxol ingredients.

Therefore, it's possible to reinvent taxol production. The next important step is to find the perfect replacement producer to relieve the Yew Trees of their noble duty.

Rethink the Production Process

New producer will dramatically increase taxol production, allow Pacific Yew Trees a permanent break from overharvest and danger of extinction.

Bacteria!

Bacterial Production in a controlled lab is safe and sustainable, with a dramatically larger yield!

At Duke iGEM, we have already begun the process of sequentially arranging these genes and growing bacteria with these new powers.

We believe our idea is implementable and has a revolutionary positive impact on future treatments of cancer, saving more lives at a lower cost.

@ 2016 Duke University iGEM