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Team:Imperial College London/Project Overview
From 2009.igem.org
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=The Problem= | =The Problem= | ||
<!--[[Image:II09_Theproblem2.png|220px|right]]--> | <!--[[Image:II09_Theproblem2.png|220px|right]]--> | ||
| - | The inspiration behind <b><i>The E.ncapsulator</i></b> was the inherent difficulty in delivering protein pharmaceuticals to the gut. Due to the delicate nature of proteins and the highly acidic environment present in the stomach, | + | The inspiration behind <b><i>The E.ncapsulator</i></b> was the inherent difficulty in delivering protein pharmaceuticals to the gut. Due to the delicate nature of proteins and the highly acidic environment present in the stomach, protein molecules are readily broken down - making oral drug delivery of protein pharmaceuticals impossible.<br> |
There are several diseases that are treated using oral delivery of peptides. Among these are: | There are several diseases that are treated using oral delivery of peptides. Among these are: | ||
| - | + | Malnutrition (world hunger) and Phenylketonuria (PKU), a disease associated with mental retardation due to insufficient ability to metabolize phenylalanine. | |
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==Some statistics== | ==Some statistics== | ||
| - | In | + | In this project, one of our applications is on synthesising phenylalanine hydroxylase (PAH), an enzyme responsible for metabolism of phenylalanine in PKU patients. Furthermore, we propose to synthesise cellulase and deliver cellulase as a wacky solution to the world hunger problem. In practice, <b><i>The E.ncapsulator</i></b> system is a generic drug production and delivery platform. This means that potentially, we are capable of solving any problem that tackles the delivery of polypeptides to the small intestine. |
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{| style="color:#CCC; background-color:#325d97;" cellpadding="6" cellspacing="0" border="3" | {| style="color:#CCC; background-color:#325d97;" cellpadding="6" cellspacing="0" border="3" | ||
| - | ! Malnutrition (from [ | + | ! Malnutrition (from [1]) |
| - | ! PKU (from [ | + | ! PKU (from [2]) |
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| 820 million are in developing countries | | 820 million are in developing countries | ||
| - | | | + | | Prevalance Rate: approx 1 in 10,000 or 0.01% or 27,200 people in USA. |
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<area coords="0,74,32,91" onmouseover="return overlib('Module 2 is the encapsulation module of the system. The cell is programmed to secrete a protective capsule around itself in what we have dubbed 'autoencapsulation.' This protects <b><i>The E.ncapsulator</i></b> in its passage through the stomach. Additionally, we have added genes which allow for the production of trehalose, a protective sugar that aids in the storage of the cell.');" onmouseout="return nd();"> | <area coords="0,74,32,91" onmouseover="return overlib('Module 2 is the encapsulation module of the system. The cell is programmed to secrete a protective capsule around itself in what we have dubbed 'autoencapsulation.' This protects <b><i>The E.ncapsulator</i></b> in its passage through the stomach. Additionally, we have added genes which allow for the production of trehalose, a protective sugar that aids in the storage of the cell.');" onmouseout="return nd();"> | ||
| + | <area coords="34,74,66,91" onmouseover="return overlib('RcsAB transcriptional dual regulator activates transcription from associated promoter<br><b>Distance to transcription start site:</b> -125.5 (ranging from -132 to -119)<br><b>Evidence:</b> Binding of cellular extracts, Site mutation [Wehland00], Binding of purified proteins [Wehland00]');" onmouseout="return nd();"> | ||
| + | <area coords="147,0,200,17" onmouseover="return overlib('GadE transcriptional activator activates transcription from associated promoter<br>The exact location of this binding site is unknown or not specified.<br><b>Evidence:</b> Binding of purified proteins [Hommais04], Gene expression analysis [Hommais04]');" onmouseout="return nd();"> | ||
<area coords="104,60,185,101" onmouseover="return overlib('bladibla);" onmouseout="return nd();"> | <area coords="104,60,185,101" onmouseover="return overlib('bladibla);" onmouseout="return nd();"> | ||
| - | + | <area coords="24,0,184,108" onmouseover="return overlib('<b>Operon:</b> rcsAp (Experim. ev.) <BR><b>Tr.Activators:</b> (GadE RcsAB) <BR><b>Tr.Inhibitors:</b> (Hns)');" onmouseout="return nd();"> | |
| + | <area coords="0,0,184,108" onmouseover="return overlib('<b>Operon</b>: rcsA');" onmouseout="return nd();"> | ||
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| - | == | + | ==Manufacturing Considerations== |
*<b>Synthesis:</b> The system is generic and potentially able to manufacture any type of polypeptide. | *<b>Synthesis:</b> The system is generic and potentially able to manufacture any type of polypeptide. | ||
*<b>Purification:</b> In The E.ncapsulator, polypeptide synthesis (Module 1) and encapsulation of the cells(Module 2) occur in the same place. This dual production and delivery platform means that there is no need for expensive downstream purification processes. | *<b>Purification:</b> In The E.ncapsulator, polypeptide synthesis (Module 1) and encapsulation of the cells(Module 2) occur in the same place. This dual production and delivery platform means that there is no need for expensive downstream purification processes. | ||
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=Major Results= | =Major Results= | ||
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| + | =Achievements= | ||
=References= | =References= | ||
| - | [1 | + | [1][http://www.worldhunger.org/articles/Learn/world%20hunger%20facts%202002.htm World Hunger]<br> |
| - | + | [2][http://www.wrongdiagnosis.com/p/phenylketonuria/stats.htm Phenylketonuria]<br> | |
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<hr> | <hr> | ||
| - | <center><b>These links may be useful to browse our results and achievements: </b></center> | + | <center><b>Pushed for time? These links may be useful to quickly browse our results and achievements: </b></center> |
<html><center><a href="https://2009.igem.org/Team:Imperial_College_London/Major_results"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage2.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Wetlab/BioBricks"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage3.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Achievements"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage4.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Manufacturing_Considerations"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage5.png"></a><html><a | <html><center><a href="https://2009.igem.org/Team:Imperial_College_London/Major_results"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage2.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Wetlab/BioBricks"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage3.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Achievements"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage4.png"></a><a href="https://2009.igem.org/Team:Imperial_College_London/Manufacturing_Considerations"><img style="vertical-align:bottom;" width="19%" src="http://i691.photobucket.com/albums/vv271/dk806/II09_Homepageimage5.png"></a><html><a | ||
Revision as of 10:36, 20 October 2009
Contents |
The Problem
The inspiration behind The E.ncapsulator was the inherent difficulty in delivering protein pharmaceuticals to the gut. Due to the delicate nature of proteins and the highly acidic environment present in the stomach, protein molecules are readily broken down - making oral drug delivery of protein pharmaceuticals impossible.
There are several diseases that are treated using oral delivery of peptides. Among these are:
Malnutrition (world hunger) and Phenylketonuria (PKU), a disease associated with mental retardation due to insufficient ability to metabolize phenylalanine.
Some statistics
In this project, one of our applications is on synthesising phenylalanine hydroxylase (PAH), an enzyme responsible for metabolism of phenylalanine in PKU patients. Furthermore, we propose to synthesise cellulase and deliver cellulase as a wacky solution to the world hunger problem. In practice, The E.ncapsulator system is a generic drug production and delivery platform. This means that potentially, we are capable of solving any problem that tackles the delivery of polypeptides to the small intestine.
| Malnutrition (from [1]) | PKU (from [2]) |
|---|---|
| 854 million people worldwide are undernourished (12.6% of the world population) | 1 per 10,000 - 15,000 newborns are diagnosed with phenylketonuria in the USA |
| 820 million are in developing countries | Prevalance Rate: approx 1 in 10,000 or 0.01% or 27,200 people in USA. |
Our Solution
The E.ncapsulator is a novel protein manufacture and delivery platform designed to overcome these difficulties. In order to learn more about each module of the system and what its doing, hover over the different parts of the image below:
Manufacturing Considerations
- Synthesis: The system is generic and potentially able to manufacture any type of polypeptide.
- Purification: In The E.ncapsulator, polypeptide synthesis (Module 1) and encapsulation of the cells(Module 2) occur in the same place. This dual production and delivery platform means that there is no need for expensive downstream purification processes.
- Storage: Freeze drying in the encapsulation phase and secondary encapsulation allow for storage of The E.ncapsulator.
- Quality Control: If one cell fails to produce the polypeptide of interest, it will have minimal impact on the whole system. In that if one cell fails to produce any protein it will have a minimal impact on the whole system.
- Safety: In order to reduce risks associated with our product, we have chosen a GRAS (generally recognized as safe) chassis. Furthermore, all the genetic material is destroyed prior ingestion to prevent any risks of horizontal gene transfer after colonisation by the bacteria.
Major Results
Achievements
References
[1][http://www.worldhunger.org/articles/Learn/world%20hunger%20facts%202002.htm World Hunger]
[2][http://www.wrongdiagnosis.com/p/phenylketonuria/stats.htm Phenylketonuria]
