Difference between revisions of "Team:Harvard BioDesign/Project"

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               <p>
 
               <p>
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                 Colon cancer is the second leading cause of cancer death in the United States. Each year, almost 140,000 people
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                 Colon cancer is the second most fatal cancer in the United States. Nearly 140,000 people
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                 are diagnosed with colon cancer, and 50,000 people die from the disease. Diagnosis and treatment often require invasive
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                 are diagnosed, and 50,000 people die, from the disease annually. Diagnosis and treatment often require invasive
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                 procedures, including colonoscopies and surgery. Less invasive treatments such as chemotherapy cause unpleasant side
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                 procedures, including colonoscopies and surgery. Alternatively, treatment with chemotherapy is much less specific
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                effects. We turn to synthetic biology to develop a better colon cancer therapy. An ideal cell-based therapy would have
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and causes very serious side effects. An ideal cell-based therapy would have two significant components- a way to target, and a way to specifically kill cancer cells.
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                two significant components: a way to kill cancer cells, and a way to specifically target them. In our quest to find a way
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            </p>
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                to specifically target cancer cells, we found that the problem of controlling a cell’s interaction with its physical
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                environment extended beyond cancer therapy into a myriad of biological contexts. Harvard iGEM 2015 focuses on building a
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                platform for controlling specific bacterial adhesion in a variety of biological settings, including colon cancer therapy.
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              </p>
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             </div>
 
             </div>
 
           </section>
 
           </section>
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           <section class="two">
 
           <section class="two">
 
             <div class="container">
 
             <div class="container">
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               <img src="https://static.igem.org/mediawiki/2015/8/8e/Harvard2015Closer.png" alt="magnify" style="width:200px;height:200px"/>
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               <img src="https://static.igem.org/mediawiki/2015/6/65/Harvard2015SynBio.png" alt="Colon Tumor"/>
 
               <header><h2>Looking <i>Closely</i> at the Problem</h2></header>
 
               <header><h2>Looking <i>Closely</i> at the Problem</h2></header>
 
               <p>
 
               <p>
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                 Explanation of how we thought through potential solutions in the context of the microbiome.
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                 As synthetic biologists we think of the gut a bit...differently. We see the bacteria who live there as a resource that can be used to fight colon cancer. With the power of synthetic biology, which gives us tools to control cellular processes, we believed we could develop a system which could target and treat colon cancer. However, as we thought about our project, we realized that our biggest hurdle was the issue of targeting. While we we had tools to control what happened inside a cell, we lacked the ability to control how a cell interacts with its physical environment. Overcoming this relevant well beyond the realm of cancer therapy and has significance for a myriad of biological contexts. Harvard iGEM 2015 thus focused on building a platform for controlling specific bacterial adhesion in a variety of biological settings, including colon cancer therapy.
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                Statistics and links to external sites about the prevalence of bacteria in the gut. Motivations
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              </p>
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                from the perspective of synthetic biology to address the problem of colon cancer with the power
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                of synthetic biology. However, we’re unable to use the power of synthetic biology.
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              </p>
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             </div>
 
             </div>
 
           </section>
 
           </section>
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           <section class="three">
 
           <section class="three">
 
             <div class="container">
 
             <div class="container">
−
              <img src="https://static.igem.org/mediawiki/2015/6/65/Harvard2015SynBio.png" alt="Colon Tumor"/>
 
 
               <header><h2>Inspiration from Nature  - Type 1 Pili</h2></header>
 
               <header><h2>Inspiration from Nature  - Type 1 Pili</h2></header>
 
               <p>
 
               <p>
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                 Enter Type 1 fimbriae. Start by saying that interaction with the physical environment is a
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                 Nature has been working on the problem of bacterial adhesion for billions of years. We looked there for inspiration and found a durable structure on bacteria we thought we could adapt for our purposes, mimicking nature's design. That structure is called Type 1 Pili. In biological systems Type 1 Pili
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                huge problem in nature and has been worked on for billions of years. Make clear that we’re
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                inspired by nature and that we’re mimicking nature’s design. In biological systems Type 1 Pili
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                 typically manifest as organelles on the surface of pathogenic E. coli which are responsible for
 
                 typically manifest as organelles on the surface of pathogenic E. coli which are responsible for
 
                 urinary tract infections in humans. The pili are translated from the “Fim” system of genes in the
 
                 urinary tract infections in humans. The pili are translated from the “Fim” system of genes in the
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                 nm in length, which are attached to two adapter proteins (FimF and FimG) and finally the FimH
 
                 nm in length, which are attached to two adapter proteins (FimF and FimG) and finally the FimH
 
                 adhesin at the end of the pilus. The role which the pili play in these infections follows from its
 
                 adhesin at the end of the pilus. The role which the pili play in these infections follows from its
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                 structure. FimH contains a mannose-binding domain which binds to mannose-containing receptors in
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                 structure. FimH is "sticky" due to a pocket which binds to a sugar called mannose which is expressed on the surface of most eukaryotic cells, including those in the urinary tract.
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                host cells in the urinary tract epithelial tissue, activating a phagocytic process within the cells,
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                 <sup>22</sup></p>
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                 leading to bacterial invasion and replication in the host cells<sup>22</sup>.</p>
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               <br>
 
               <br>
 +
              <img src="https://static.igem.org/mediawiki/2015/2/2b/Harvard2015CloseUp.png" style="width:550px;height:350px" />
 
               <p>
 
               <p>
 
                 In the Fim genetic circuit, the FimE and FimB recombinases play an especially significant role in
 
                 In the Fim genetic circuit, the FimE and FimB recombinases play an especially significant role in
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           <section class="four">
 
           <section class="four">
 
             <div class="container">
 
             <div class="container">
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               <img src="https://static.igem.org/mediawiki/2015/2/2b/Harvard2015CloseUp.png" style="width:550px;height:350px" />
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               <img src="https://static.igem.org/mediawiki/2015/e/ec/Harvard_Research_Process.png" alt="Research Process" style="width:400px;height:400px;margin-top:-10px;margin-bottom:35px;border:1px solid darkgrey;"/>
 
               <header><h2>Controlling Bacterial Adhesion</h2></header>
 
               <header><h2>Controlling Bacterial Adhesion</h2></header>
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               <p>(Our Approach)</p>
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               <p>Our Approach:</p>
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              <p>-Find a Binding Peptide </p>
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              <p>-Insert Peptide into FimH </p>
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              <p>-Test for specific binding!</p>
 
             </div>
 
             </div>
 
           </section>
 
           </section>
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           <section class="five">
 
           <section class="five">
 
             <div id="platform" class="container">
 
             <div id="platform" class="container">
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              <img src="https://static.igem.org/mediawiki/2015/e/ec/Harvard_Research_Process.png" alt="Research Process" style="width:400px;height:400px;margin-top:-10px;margin-bottom:35px;border:1px solid darkgrey;"/>
 
 
               <header><h2>A Toolkit</h2></header>
 
               <header><h2>A Toolkit</h2></header>
 
               <p>
 
               <p>
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                 Textual elaboration of the graphic. We won’t go into detail on the construct design here or the fusion
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                 We developed a platform for controllable, specific adhesion that can be used to control how there biological designs interact with there physical environment. Our platform is modular, specific and customizable.  
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                sites on fimH; speak generally to the spirit and inspiration of our process, emphasize graphically the
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                modularity and reusability of the system.
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               </p>
 
               </p>
 
               <br>
 
               <br>
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                 The problem of controlled bacterial adhesion spans biology and we mean to solve it! Our approach and
 
                 The problem of controlled bacterial adhesion spans biology and we mean to solve it! Our approach and
 
                 the biobricks we have submitted to the registry will be a resource for future iGEM teams to control
 
                 the biobricks we have submitted to the registry will be a resource for future iGEM teams to control
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                 adhesion in a myriad of contexts.
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                 adhesion in a myriad of contexts.You can decide what to BactoGrip!
 
               </p>
 
               </p>
 
               <footer>How do you use BactoGrip, you ask?<br/>
 
               <footer>How do you use BactoGrip, you ask?<br/>
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               <header>
 
               <header>
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                 <h2>Gripping Applications</h2>
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                 <h2>Gripping Applications- How Did We Use BactoGrip?</h2>
 
               </header>
 
               </header>
 
               <footer>
 
               <footer>

Revision as of 03:41, 19 September 2015


Prologue by HTML5 UP

Project Logo

BactoGrip: Where we began

Colon cancer is the second most fatal cancer in the United States. Nearly 140,000 people are diagnosed, and 50,000 people die, from the disease annually. Diagnosis and treatment often require invasive procedures, including colonoscopies and surgery. Alternatively, treatment with chemotherapy is much less specific and causes very serious side effects. An ideal cell-based therapy would have two significant components- a way to target, and a way to specifically kill cancer cells.

Colon Tumor

Looking Closely at the Problem

As synthetic biologists we think of the gut a bit...differently. We see the bacteria who live there as a resource that can be used to fight colon cancer. With the power of synthetic biology, which gives us tools to control cellular processes, we believed we could develop a system which could target and treat colon cancer. However, as we thought about our project, we realized that our biggest hurdle was the issue of targeting. While we we had tools to control what happened inside a cell, we lacked the ability to control how a cell interacts with its physical environment. Overcoming this relevant well beyond the realm of cancer therapy and has significance for a myriad of biological contexts. Harvard iGEM 2015 thus focused on building a platform for controlling specific bacterial adhesion in a variety of biological settings, including colon cancer therapy.

Inspiration from Nature - Type 1 Pili

Nature has been working on the problem of bacterial adhesion for billions of years. We looked there for inspiration and found a durable structure on bacteria we thought we could adapt for our purposes, mimicking nature's design. That structure is called Type 1 Pili. In biological systems Type 1 Pili typically manifest as organelles on the surface of pathogenic E. coli which are responsible for urinary tract infections in humans. The pili are translated from the “Fim” system of genes in the E. coli genome. Formation of individual pili consists of a “chaperone-usher” pathway whereupon a fimD “chaperone” protein binds to a subunit of the pili and “ushers” it through a membrane pore to bind it to the elongating pilus. Repeating fimA subunits form the base of a helical rod roughly 7 nm in length, which are attached to two adapter proteins (FimF and FimG) and finally the FimH adhesin at the end of the pilus. The role which the pili play in these infections follows from its structure. FimH is "sticky" due to a pocket which binds to a sugar called mannose which is expressed on the surface of most eukaryotic cells, including those in the urinary tract. 22


In the Fim genetic circuit, the FimE and FimB recombinases play an especially significant role in regulating expression of the Fim system and the resulting pili production. Containing an invertible 314-bp element called the “Fim switch,” the system is only able to be transcribed by the promoter when this switch is in the “on” orientation. FimE and FimB are located upstream of the rest of the Fim operon subunits.

Research Process

Controlling Bacterial Adhesion

Our Approach:

-Find a Binding Peptide

-Insert Peptide into FimH

-Test for specific binding!

A Toolkit

We developed a platform for controllable, specific adhesion that can be used to control how there biological designs interact with there physical environment. Our platform is modular, specific and customizable.


Usage

The problem of controlled bacterial adhesion spans biology and we mean to solve it! Our approach and the biobricks we have submitted to the registry will be a resource for future iGEM teams to control adhesion in a myriad of contexts.You can decide what to BactoGrip!

Gripping Applications- How Did We Use BactoGrip?