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Team:Uppsala/Safety
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| - | document.getElementById("tab1").innerHTML = '<p> | + | document.getElementById("tab1").innerHTML = '<h2>Gene Design</h2><p>Bacteria are able to do some amazing things and with gene technology we can even program them to do what we want, like producing medicines. But this power also comes with responsibility since they could become dangerous if programmed in a certain way. When inserting a gene into a bacteria there are some things to consider:</p><br><br>Where does the gene come from? <br>What is its normal function?<br>What is the function of similar genes?<br><br>If the gene comes from a pathogen you should make sure you know what it’s effect are on virulence. And if it’s function is normally non-pathogenic but the gene is related to or can interact with some virulence factors you will have to take that into account.<br><br>This year Uppsala synthesised codon optimised genes from two class 2 bacteria. The YenR transcription factor from <i>Yersinia enterocolitica</i> and the Colicin Fy bacteriocin from <i>Yersinia frederiksenii</i>. YenR was not directly involved in causing virulence though it could play a role in regulating factors specific for <i>Y. enterocolitica.</i> Therefore we deemed it safe to use in <i>E. coli.</i> The colicin from <i>Y.frederiksenii</i> is stated to be specific towards <i>Y.enterocolitica</i>, however the documentation is poor. This might mean that the expressed colicin is at a higher risk of causing disease than normal lab strains of <i>E.coli</i>. Therefore lab work should be done extra carefully when working with the colicin expressing bacteria and colicin. We decided not to class this extra possible toxicity as a Class 2 bacteria due to its origin as a colicin, which are known to be specific to bacterias.</p><h2>Collagen-like fusion protein on the surface of <i>E.coli</i></h2><p>When designing a construct using genes expressing human-like proteins, great precautions need to be taken in consideration due to possible interactions with the human body. <br><br>While synthesizing a collagen-like protein <sup><a href="#reference1">[1]</a></sup> for the probiotic bacteria to express on its surface a great deal of investigation was spent on finding out what other mechanisms could get involved in interacting with the protein in our body apart from the pathogen we were targeting. Is it safe to express proteins resembling our own in a safety 1 lab? What could be the consequences of this modified bacteria entering our biological system? What was the ultimate problem with collagen that made us abandon the development of this construct?<br><br>At first glance, a mimicry of the adhesion system used by <i>Y. enterocolitica</i> to bind to our cells using collagen on the surface of its outer membrane would give an immerse advantage in targeting the pathogen. It would even inhibit the pathogen to bind to human cells as the bonding created in between the collagen-like protein to the invasin membrane protein on <i>Y. enterocolitica</i> is greater than the one formed with human collagen. <sup><a href="#reference2">[2]</a></sup> Activity in the stomach and gut would give a great advantage in our targeting system. But, the problem occurs as the bacteria could with a small risk enter the body in other places where our immune system is present.<sup><a href="#reference3">[3]</a></sup><br><br>Due to this risk we never fulfilled the idea of creating an adhesion system using the collagen-like protein.</p><h2>References:</h2><ul class="reference"><li><a id="reference1">[1]</a> Squeglia, Flavia, Beth Bachert, Alfonso De Simone, Slawomir Lukomski, and Rita Berisio. "The crystal structure of the streptococcal collagen-like protein 2 globular domain from invasive M3-type group A Streptococcus shows significant similarity to immunomodulatory HIV protein gp41." Journal of Biological Chemistry 289, no. 8 (2014): 5122-5133.</li><li><a id="reference2">[2]</a> Rutschmann, Christoph, Stephan Baumann, Jürg Cabalzar, Kelvin B. Luther, and Thierry Hennet. "Recombinant expression of hydroxylated human collagen in Escherichia coli." Applied microbiology and biotechnology 98, no. 10 (2014): 4445-4455.</li><li><a id="reference3">[3]</a> Professor Lars Hellman from Uppsala Universitet</li></ul>'; |
Revision as of 12:54, 16 October 2014
Stephanie Herman
Teresa Reinli
Joakim Hellner
Alexander Virtanen
Jennifer Rosenius
Marcus Hong
Miranda Stiernborg
Tim Hagelby Edström
Viktor Blomkvist
Megha Biradar
Niklas Handin
Jonas Mattisson
Arina Gromov
Nils Anlind
Eric Sandström
Gunta Celma
Oliver Possnert
Martin Friberg
Kira Karlsson
Christoffer Andersson
Laura Pacoste
Andries Willem Boers
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