Difference between revisions of "Team:Aachen"

 
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<img src="https://static.igem.org/mediawiki/2018/c/cb/T--Aachen--homepage.jpg" class="img-index img-responsive" alt="Here you should see a team picture">
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<h3>Our project</h3>
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<p>
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We, the iGEM team Aachen 2018, are addressing a medical issue that has gained tremendous importance in past decades:
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the diagnosis of melatonin under- and overproduction. Melatonin is primarily known as a sleep hormone. However, as the endocrine research reveals,
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melatonin regulates all aspects of human physiology: day-night cycle, immune function, hormone release, muscle growth,
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and reproduction are some of the many physiological properties that melatonin regulates. <!-- KOMMENTAR:
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Sollte Dr. Michael Colgan noch mit meiner korrekten Qulle aus einem scientific paper auf meine Facebook message (Henri)
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oder mail (iGEM) antworten, können wir folgenden Satz noch mit rein nehmen: "It is estimated,
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that around 20% of the human genome is regulated by melatonin, making it he largest control system in human physiology."
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(Orginaltext aus seinem Fabebook-Beitrag: "[...] This activity uses daily expression of over 20% of your total genome,
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making melatonin the largest control system in human physiology. [...]" - Dr. Michael Colgan) -->
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Underproduction of melatonin is primarily associated with insomnia. However, melatonin also plays an essential role in
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neurodegenerative diseases (Alzheimer's and Parkinson's disease), psychological disorders (depression and schizophrenia) and fibromyalgia.
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Melatonin acts antiproliferative on inflammations, reduces reactive oxygen species and has oncostatic properties.<br>
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Our innovative approach solves the problems of the current melatonin measurements.
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Providing a faster, cheaper and a more versatile method, is our core motivation.
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<h3><p>Who are we?</p></h3>
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<p> In the following months we will be developing a yeast-based biosensor for the sleeping hormone melatonin. Melatonin regulates the circadian rhythm and plays an important role in depression, Alzheimer’s and Parkinson’s disease. Therefore, we want to facilitate melatonin measurement by building a less expensive biosensor which can be used without special laboratory equipment.</p>
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For our project we got a Gold medal as well as a nomination for the Best Hardware for our Spectrometer and LSPR device.
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<h3><p>Scientific approach:</p></h3>
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</p>
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<p>Our approach is to genetically modify Saccharomyces cerevisiae by integrating a highly specific human melatonin receptor into the cells. This will allow us to detect melatonin from a saliva sample without previous purification. To get a signal from the melatonin binding, we will use two different signalling systems:</p>
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<h5><p>Using a nuclear receptor and a reporter gene:</p></h5>
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<p>The membrane permeability for melatonin is high. This permits us to use the nuclear retinoid z receptor (RZR) which is directly regulating gene expression. As the genes regulated by RZR do not exist in S. cerevisiae, we plan to create a chimeric receptor consisting of the RZR and the recognition sequence of the human estrogen receptor alpha (ERα). When melatonin is bound, the modified receptor can bind to the estrogen receptor responsive element (ERE) and as a consequence regulate expression of firefly luciferase reporter genes. The signal intensity of luciferase is dose-dependent in the presence of ligands.</p>
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<h5><p>Enzyme-Fragment Complementation Assay:</p></h5>
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<p>When melatonin binds to the G protein-coupled receptor MT1, β-arrestins can be recruited. We are going to use this mechanism by designing two fusion-proteins: on the one hand the MT1 receptor will be fused to a fragment of an enzyme, on the other hand, the complementing enzyme fragment will be fused to the β-arrestin. Thus, receptor activation leads to β-arrestin recruitment and therefore to the formation of an active enzyme.</p>
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<img src="https://static.igem.org/mediawiki/igem.org/4/4b/2018_igem_gold_medal.svg" style="height: 100px!important; width: auto; margin-right: 100px;">
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<img src="https://static.igem.org/mediawiki/2018/7/77/T--Aachen--melasense_device.png" style="height: 100px!important; width: auto; margin-left:100px;">
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<h3>Key achievements</h3>
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<p>
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&#10004; Developed a concept for a novel biological and cell-free melatonin biosensor<br>
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    &#10004; Modified the DNA binding site of a melatonin sensitive transcription receptor<br>
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    &#10004; Expressed the melatonin sensitive receptor in <em>Escherichia coli</em><br>
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    &#10004; Modeled our cell and cell-free approaches precisely<br>
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    &#10004; Built first iGEM ever spectrometer with a resolution of 4 nm<br>
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    &#10004; Successfully hosted a biotechnology conference in collaboration with iGME Utrecht<br>
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</p>
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<h3>Human Practices</h3>
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<p>To bring our project forward, we integrated feedback from experts of different backgrounds in our project.
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Therefore, we engaged in dialogues with medical and engineering professionals, as well as discussed the rights of melatonin deficiency treatments with the Medicines Evaluation Board. <br></br>
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Besides, involving youth with synthetic biology was a part of our human practice. We cooperated with Germany's greatest scientific student competition "Jugend Forscht", the DAAD (German Academic Exchange Service) and a school. <br>
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Collaborations and meetups enabled us to unite internationally. <br></br>
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We  also took part in the international March for Science to demonstrate for free accessibility of scientific research, met Emmanuelle Charpentier and by radio, we raised awareness for melatonin-related diseases.
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</p>
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<a href="https://2018.igem.org/Team:Aachen/Human_Practices">Learn more about our public engagement.</a> <br></br>
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<h3>Wetlab</h3>
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<img class="img-fluid" src="https://static.igem.org/mediawiki/2018/4/47/T--Aachen--Teaser-Lab.jpg">
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<p>
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During the last five months, the team experienced a new style of "life", we updated our biosafety level and got a new first home.
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In the laboratory, gloves and tips, western blots and electrophoresis gels, were part of our new daily routine.
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We thought, worked and lived together. Get to know our lab successes and failures in this <a href="https://2018.igem.org/Team:Aachen/Wetlab/Notebook">
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chronologic weekly overview</a>.
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</p>
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<div class="container-fluid">
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<div class="row justify-content-center indexbox">
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<h3>Hardware</h3>
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<p> For detection of melatonin in saliva, we decided to use LSPR. For this a spectrometer was built, so we are able to see changes in the refraction index,
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due to fine changes in the composition of the medium.
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LSPR makes our sensor a very sensitive device, while a gold nano structure with the binding domain of RZR with streptavidin and biotin is responsible for
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the high selectivity.<br>
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As most of the components of our hardware can be used multiple times, the sensor is very cost efficient.<br>
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To learn more about our hardware project, please take a look at our <a href="https://2018.igem.org/Team:Aachen/Hardware/Overview">Hardware page</a></p>
  
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Latest revision as of 14:36, 28 November 2018

Here you should see a team picture

Our project

We, the iGEM team Aachen 2018, are addressing a medical issue that has gained tremendous importance in past decades: the diagnosis of melatonin under- and overproduction. Melatonin is primarily known as a sleep hormone. However, as the endocrine research reveals, melatonin regulates all aspects of human physiology: day-night cycle, immune function, hormone release, muscle growth, and reproduction are some of the many physiological properties that melatonin regulates. Underproduction of melatonin is primarily associated with insomnia. However, melatonin also plays an essential role in neurodegenerative diseases (Alzheimer's and Parkinson's disease), psychological disorders (depression and schizophrenia) and fibromyalgia. Melatonin acts antiproliferative on inflammations, reduces reactive oxygen species and has oncostatic properties.
Our innovative approach solves the problems of the current melatonin measurements. Providing a faster, cheaper and a more versatile method, is our core motivation.


For our project we got a Gold medal as well as a nomination for the Best Hardware for our Spectrometer and LSPR device.


Key achievements

✔ Developed a concept for a novel biological and cell-free melatonin biosensor
✔ Modified the DNA binding site of a melatonin sensitive transcription receptor
✔ Expressed the melatonin sensitive receptor in Escherichia coli
✔ Modeled our cell and cell-free approaches precisely
✔ Built first iGEM ever spectrometer with a resolution of 4 nm
✔ Successfully hosted a biotechnology conference in collaboration with iGME Utrecht

Human Practices

To bring our project forward, we integrated feedback from experts of different backgrounds in our project. Therefore, we engaged in dialogues with medical and engineering professionals, as well as discussed the rights of melatonin deficiency treatments with the Medicines Evaluation Board.

Besides, involving youth with synthetic biology was a part of our human practice. We cooperated with Germany's greatest scientific student competition "Jugend Forscht", the DAAD (German Academic Exchange Service) and a school.
Collaborations and meetups enabled us to unite internationally.

We also took part in the international March for Science to demonstrate for free accessibility of scientific research, met Emmanuelle Charpentier and by radio, we raised awareness for melatonin-related diseases.

Learn more about our public engagement.

Wetlab

During the last five months, the team experienced a new style of "life", we updated our biosafety level and got a new first home. In the laboratory, gloves and tips, western blots and electrophoresis gels, were part of our new daily routine. We thought, worked and lived together. Get to know our lab successes and failures in this chronologic weekly overview.

Hardware

For detection of melatonin in saliva, we decided to use LSPR. For this a spectrometer was built, so we are able to see changes in the refraction index, due to fine changes in the composition of the medium. LSPR makes our sensor a very sensitive device, while a gold nano structure with the binding domain of RZR with streptavidin and biotin is responsible for the high selectivity.
As most of the components of our hardware can be used multiple times, the sensor is very cost efficient.
To learn more about our hardware project, please take a look at our Hardware page