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   <title>iGEM Manchester - Graz Project</title>
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<h1 style="margin-bottom: 60px;"> Project Outlines</h1>
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<p style="text-align:justify">iGEM Manchester-Graz’s objective as a team is to find a better way to treat and alleviate the symptoms of Parkinson’s disease (PD) through the use of synthetic biology. Degradation of dopaminergic neurons and therefore low levels of dopamine is the main cause of Parkinson’s disease (PD), for which the current treatment involves oral doses of L-DOPA (or levodopa), which unlike dopamine itself is able to cross the blood-brain-barrier. Within the brain L-DOPA is enzymatically converted into dopamine and therefore able to relieve many of the motor symptoms of PD (Figure 1).</p><div id="pictureright"> <img src="https://static.igem.org/mediawiki/2015/b/b3/Manchester-Graz_Human-Gutbacteria.jpg" alt="human gut bacteria" width="400"> <br> <b> Fig 1 </b>Administration of L-DOPA via bacteria in the patient's gut</div>
 
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<p style="text-align:justify">Our aim is to take the first steps in the development of a novel technology of drug delivery by developing self-regulating drug-producing bacterial strains that, in the future, could be incorporated into patients’ gut microflora to secrete medicines directly inside the body. To control the bacterial L-DOPA production, we plan to develop a multidimensional cell density dependent auto-regulation system that could also be used to control other multistep enzyme pathways.</p>
 
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<div id="pictureleft"><img src="https://static.igem.org/mediawiki/2015/e/ef/Manchester-Graz_Pathway.jpg" alt="Pathway" width="300"> <br><b> Fig 2 </b>dopamine and L-DOPA biosynthesis pathways</div>
 
  
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<p style="text-align:justify">The Manchester section of the team are working on L-DOPA and dopamine biosynthesis in <i>E. coli </i>BL21 and Nissle 1917 via various enzyme pathways. The focus is on three enzyme pathways, the main one being the conversion of L-tyrosine to L-DOPA via tyrosine hydroxylase and tyrosinase. In addition we are also synthesising dopamine in two different ways using aromatic amino acid decarboxylase, cytochrome P450 and transaminase. Although the primary goal would be to implement the L-DOPA synthesis within patients, we also aim to create a greener, more efficient way of the industrial synthesis of each of the above products using our modified bacteria. (Figure 2) </p>
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<p style="text-align:justify">The Graz section are using two quorum sensing based mechanisms for an auto-regulated and time shifted consecutive induction of protein expression, first demonstrated using fluorescent protein synthesis (Figure 3). The fluorescent protein could then be exchanged with genes for the L- DOPA production such that at low cell density levels tyrosine synthesis will be channeled. After a certain biomass is reached actual L-DOPA production will be induced. </p>
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<div id="pictureright"><img src="https://static.igem.org/mediawiki/2015/4/4f/Manchester-Graz_Cell_density.jpg" alt="cell%20density" width="400"><br><b>Fig 3 </b> Fluorescent protein synthesis dependent on different levels of cell density</div>
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<p style="text-align:justify">Looking to the future this system could be further utilized to activate suicide genes in <i>E.coli </i>to avoid possible overgrowth of the native intestinal flora, which we aim to show proof of concept in both strains common to academic research as well as probiotics, specifically BL21 and Nissle 1917 respectively. Even though we cannot regulate the proliferation of our engineered strain yet, it allows us to provide an outlook of a possible application as a self-regulating drug dispensing system in the GI tract, which may have clinical applications in the future.</p>
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<p style="text-align:justify">Throughout the course of the project we also aim to shape our actions in accordance to the opinions of academics, charities, industry leaders and the public. This includes what implications our project will have for patients both economically and in terms of quality of life and whether the real world implementation of this technology is feasible. We will also compare ethical opinions throughout outreach about our project and synthetic biology in general across the two countries our team spans and assess this in a wider sociological context. We feel as a team that the issues and human practices surrounding our project are just as important as the project itself and as such we endeavour to tackle a wide selection of concerns.</p>
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<h3>Manchester-Graz: the first inter-European iGEM team</h3>
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<img src="https://static.igem.org/mediawiki/2015/c/c7/Manchester-Graz_Graz.jpg" alt="graz" width="400" height="267"><br> <center><b>Graz</b></center>
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<p>Due to existing collaboration between the University of Manchester and the Graz University of technology in several research programs, such as CHEM21 and KYROBIO (European research projects), we came together as the first truly international cross-country iGEM team, supervised by professors Eriko Takano, Rainer Breitling and Sabine Flitsch in Manchester, and Anton Glieder in Graz. For the Austrian postgraduate subteam, this was a chance to enter the competition for the first time, with the support of the undergraduate students from Manchester, who could build on previous iGEM experience at their university. Once the joint team was formed, weekly Skype meetings were held to agree on a project, taking advantage of the collaboration to cover a wider area of research than would be possible as individual teams. We found working together as an international team challenging, and the distance required us to find a topic that could be worked on independently whilst still achieving a common goal. Overcoming this challenge, coupled with the exchange of knowledge and experience between the sub-teams, makes working on this project all the more rewarding.</p>
  
  
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Our idea emerged from the different fields of interest of the students in Graz and Manchester, with the former wanting to generate a regulation system for protein synthesis, and the latter being more focused on medical aspects such as the synthesis of a drug. <a href="https://static.igem.org/mediawiki/2015/2/2c/Manchester-Graz_Manchester_big.jpg" target="_blank">
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<img src="https://static.igem.org/mediawiki/2015/c/cf/Manchester-Graz_TeamManc.png" alt="Manchester" width="400" height="267"><br><center><b>Manchester</b></center>
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<p>The result was a quorum sensing based system for the autonomous production of L-DOPA and dopamine, with the students in Manchester working on the synthesis of L-DOPA and the students in Graz setting up an expression system that allows autonomous induction of several target genes. Using the advantage of two teams we can apply the L-DOPA pathway directly in a new system, which can already be evaluated in a real world context. <br><br>
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There are also numerous advantages for our team outside the science. Public outreach and human practices (a particular area of interest) are more efficiently conducted across the two countries and yield more interesting data. Different attitudes towards synthetic biology and modern biotechnology can be determined on an international scale, in Austria and the United Kingdom respectively. In addition, the potential to gain valuable knowledge from interviews with experts in industry, medicine and patient care are greatly broadened as is the possibility for raising awareness about Parkinson’s and synthetic biology. <br><br>
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iGEM Subteam Graz<br>
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Latest revision as of 20:08, 17 November 2015

iGEM Manchester-Graz - Home

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Manchester-Graz: the first inter-European iGEM team

graz
Graz

Due to existing collaboration between the University of Manchester and the Graz University of technology in several research programs, such as CHEM21 and KYROBIO (European research projects), we came together as the first truly international cross-country iGEM team, supervised by professors Eriko Takano, Rainer Breitling and Sabine Flitsch in Manchester, and Anton Glieder in Graz. For the Austrian postgraduate subteam, this was a chance to enter the competition for the first time, with the support of the undergraduate students from Manchester, who could build on previous iGEM experience at their university. Once the joint team was formed, weekly Skype meetings were held to agree on a project, taking advantage of the collaboration to cover a wider area of research than would be possible as individual teams. We found working together as an international team challenging, and the distance required us to find a topic that could be worked on independently whilst still achieving a common goal. Overcoming this challenge, coupled with the exchange of knowledge and experience between the sub-teams, makes working on this project all the more rewarding.

Our idea emerged from the different fields of interest of the students in Graz and Manchester, with the former wanting to generate a regulation system for protein synthesis, and the latter being more focused on medical aspects such as the synthesis of a drug.

The result was a quorum sensing based system for the autonomous production of L-DOPA and dopamine, with the students in Manchester working on the synthesis of L-DOPA and the students in Graz setting up an expression system that allows autonomous induction of several target genes. Using the advantage of two teams we can apply the L-DOPA pathway directly in a new system, which can already be evaluated in a real world context.

There are also numerous advantages for our team outside the science. Public outreach and human practices (a particular area of interest) are more efficiently conducted across the two countries and yield more interesting data. Different attitudes towards synthetic biology and modern biotechnology can be determined on an international scale, in Austria and the United Kingdom respectively. In addition, the potential to gain valuable knowledge from interviews with experts in industry, medicine and patient care are greatly broadened as is the possibility for raising awareness about Parkinson’s and synthetic biology.