Team:SDU-Denmark/safety-b

From 2010.igem.org

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(Project safety)
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===Methode===
===Methode===
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We have used our risk-assessment paper to describe the safety of each of our contributed parts. The genes were [http://blast.ncbi.nlm.nih.gov/Blast.cgi BLASTed] to find their function and known homologs. This function was then reasearched (mainly via [http://www.ncbi.nlm.nih.gov/PubMed PubMed]), described and considered according to the questions asked in the risk-assessment paper.
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<p style="text-align: justify;">We have used our risk-assessment paper to describe the safety of each of our contributed parts. The genes were [http://blast.ncbi.nlm.nih.gov/Blast.cgi BLASTed] to find their function and known homologs. This function was then reasearched (mainly via [http://www.ncbi.nlm.nih.gov/PubMed PubMed]), described and considered according to the questions asked in the risk-assessment paper.</p>
===[http://partsregistry.org/wiki/index.php?title=Part:BBa_K343001 Monooxygenase (Part K343001)]===
===[http://partsregistry.org/wiki/index.php?title=Part:BBa_K343001 Monooxygenase (Part K343001)]===
====General use====
====General use====
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This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people. No special care is needed when working with this BioBrick.  
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<p style="text-align: justify;">This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people. No special care is needed when working with this BioBrick. </p>
====Potential pathogenicity====
====Potential pathogenicity====
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The BioBrick’s product is not in itself toxic, but we do not recommend using this BioBrick for any type of system in humans or animals for the following reasons:  
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<p style="text-align: justify;">The BioBrick’s product is not in itself toxic, but we do not recommend using this BioBrick for any type of system in humans or animals for the following reasons:  
*Retinoic acid, which retinal can degrade into, can affect gene expression and function of almost any cell, including cells of the immune system; it also plays a fundamental role in cellular functions by activating nuclear receptors ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 1]).  
*Retinoic acid, which retinal can degrade into, can affect gene expression and function of almost any cell, including cells of the immune system; it also plays a fundamental role in cellular functions by activating nuclear receptors ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 1]).  
*Vitamin A toxicity can lead to hepatic congestion and fibrosis ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 2]).  
*Vitamin A toxicity can lead to hepatic congestion and fibrosis ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 2]).  
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*Vitamin A and its derivatives have been implicated as chemopreventive and differentiating agents in a variety of cancers ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 3]).  
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*Vitamin A and its derivatives have been implicated as chemopreventive and differentiating agents in a variety of cancers ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 3]). </p>
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These effects are not directly associated with the enzyme itself, but have been observed in humans. It is highly unlikely that high enough doses can be reached with this biobrick. Please see references for more information about the diseases.  
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<p style="text-align: justify;">These effects are not directly associated with the enzyme itself, but have been observed in humans. It is highly unlikely that high enough doses can be reached with this biobrick. Please see references for more information about the diseases. </p>
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The biobrick has many homologs, that have the same function as this biobrick and is highly conserved in bacteria and eukaryotes. The biobrick does not affect the immunesystem in humans.
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<p style="text-align: justify;">The biobrick has many homologs, that have the same function as this biobrick and is highly conserved in bacteria and eukaryotes. The biobrick does not affect the immunesystem in humans.</p>
====Environmental impact====
====Environmental impact====
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To our knowledge retinal should not play a significant role in environmental processes or would disrupt natural occurring symbiosis.  
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<p style="text-align: justify;">To our knowledge retinal should not play a significant role in environmental processes or would disrupt natural occurring symbiosis. </p>
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The biobrick should not increase its host’s ability to spread, survive outside the laboratory, and will most likely decrease its ability to replicate.
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<p style="text-align: justify;">The biobrick should not increase its host’s ability to spread, survive outside the laboratory, and will most likely decrease its ability to replicate.</p>
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Beta-caroten monooxygenase is found in a wide variety of different bacteria, insects and animals ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 4]). As such we would be cautious as to letting a system containing this BioBrick into the wild, since it's function might conflict with existing systems. On the other hand one might argue that since it's function is already available in nature, the function is widely available.  
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<p style="text-align: justify;">Beta-caroten monooxygenase is found in a wide variety of different bacteria, insects and animals ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 4]). As such we would be cautious as to letting a system containing this BioBrick into the wild, since it's function might conflict with existing systems. On the other hand one might argue that since it's function is already available in nature, the function is widely available. </p>
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The product of the BioBrick, retinal, also plays an important function in nature and animals. For this reason we fell that the BioBrick could be used in controlled settings, but not in the wild.  
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<p style="text-align: justify;">The product of the BioBrick, retinal, also plays an important function in nature and animals. For this reason we fell that the BioBrick could be used in controlled settings, but not in the wild. </p>
====Possible malign use====
====Possible malign use====
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There is not reason to believe this biobrick could be used for malign uses; it does not increase the hosts ability to vaporize, create spores, regulate the immunesystem or should be pathogenic.  
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<p style="text-align: justify;">There is not reason to believe this biobrick could be used for malign uses; it does not increase the hosts ability to vaporize, create spores, regulate the immunesystem or should be pathogenic. </p>
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====General use====
====General use====
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This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people and in non-pathogenic hosts such as E. coli TOP10 or MG1655. No special care is needed when working with this BioBrick.  
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<p style="text-align: justify;">This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people and in non-pathogenic hosts such as E. coli TOP10 or MG1655. No special care is needed when working with this BioBrick. </p>
====Potential pathogenicity====
====Potential pathogenicity====
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This biobrick increases the potential of its host to move. Increased motility has been associated the bacteria’s ability to invade humans ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 5]); on the other hand it has also been shown that bacteria that loss the function of the FlhDC operon, are considerable better at colonizing the intestine ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 6]), and so an increased expression might decrease a hosts ability to colonize and invade humans. It is impossible to ensure, that this plasmid is not transferred to pathogenic bacteria since the FlhDC operons is used in a wide array of other bacteria that are known to be pathogenic.
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<p style="text-align: justify;">This biobrick increases the potential of its host to move. Increased motility has been associated the bacteria’s ability to invade humans ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 5]); on the other hand it has also been shown that bacteria that loss the function of the FlhDC operon, are considerable better at colonizing the intestine ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 6]), and so an increased expression might decrease a hosts ability to colonize and invade humans. It is impossible to ensure, that this plasmid is not transferred to pathogenic bacteria since the FlhDC operons is used in a wide array of other bacteria that are known to be pathogenic.</p>
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A number of effector cells in the human immune system react specifically to bacteria’s flagella, and so a hyperflagellated host will most likely induce a stronger immune response.  
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<p style="text-align: justify;">A number of effector cells in the human immune system react specifically to bacteria’s flagella, and so a hyperflagellated host will most likely induce a stronger immune response. </p>
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These different considerations lead us to conclude that we do not recommend using this BioBrick in humans.
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<p style="text-align: justify;">These different considerations lead us to conclude that we do not recommend using this BioBrick in humans.</p>
====Environmental impact====
====Environmental impact====
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The biobrick might increase its host ability in finding foods, but we do not think it will be able to outmatch naturally occurring bacteria. It will not increase the hosts ability to replicate, but will increase its ability to spread, which might increase its ability to survive.  
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<p style="text-align: justify;">The biobrick might increase its host ability in finding foods, but we do not think it will be able to outmatch naturally occurring bacteria. It will not increase the hosts ability to replicate, but will increase its ability to spread, which might increase its ability to survive. </p>
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The biobrick itself will most likely not make an environmental impact, since it only regulates internal systems of the bacteria.
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<p style="text-align: justify;">The biobrick itself will most likely not make an environmental impact, since it only regulates internal systems of the bacteria.</p>
====Possible malign use====
====Possible malign use====
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There is no reason to believe this BioBrick could be used for malign uses; it does not increase the host’s ability to vaporize, create spores or ability to survive under storage conditions. The fact that this BioBrick will likely increase the immune systems response to hosts carrying it makes it a bad candidate for malign use.
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<p style="text-align: justify;">There is no reason to believe this BioBrick could be used for malign uses; it does not increase the host’s ability to vaporize, create spores or ability to survive under storage conditions. The fact that this BioBrick will likely increase the immune systems response to hosts carrying it makes it a bad candidate for malign use.</p>
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====General use====
====General use====
-
This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people. No special care is needed when working with this BioBrick.  
+
<p style="text-align: justify;">This BioBrick poses no treat to the welfare of people working with it, as long as this is done in at least a level 1 safety lab by trained people. No special care is needed when working with this BioBrick. </p>
====Potential pathogenicity====
====Potential pathogenicity====
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This BioBrick consists of three different parts: The first 224 amino acid residues come from the NpSopII gene from halobacteria, encoding a blue-light photon receptor with 15 residues removed at the C-terminal. The following 9 amino acids are a linker. The last part is HtrII fused with Tsr from E. Coli. The complex' first 125 amino acid residues come from HtrII and the remaining 279 from Tsr ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 7]). NpHtrII is thought to function in signal transduction and activation of microbial signalling cascades ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 8]).   
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<p style="text-align: justify;">This BioBrick consists of three different parts: The first 224 amino acid residues come from the NpSopII gene from halobacteria, encoding a blue-light photon receptor with 15 residues removed at the C-terminal. The following 9 amino acids are a linker. The last part is HtrII fused with Tsr from E. Coli. The complex' first 125 amino acid residues come from HtrII and the remaining 279 from Tsr ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 7]). NpHtrII is thought to function in signal transduction and activation of microbial signalling cascades ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 8]).  </p>
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A single article has been written about haloarchaea in humans indicating that these played a role in patients with inflammatory bowl disease ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 9]), but there is no evidence that the genes or near homologs, this BioBrick is made from, are involved in any disease process, toxic products or invasion properties. They do not regulate the immune system in any way.
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<p style="text-align: justify;">A single article has been written about haloarchaea in humans indicating that these played a role in patients with inflammatory bowl disease ([http://2010.igem.org/Team:SDU-Denmark/safety-b#References 9]), but there is no evidence that the genes or near homologs, this BioBrick is made from, are involved in any disease process, toxic products or invasion properties. They do not regulate the immune system in any way.</p>
====Environmental impact====
====Environmental impact====
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The BioBrick does not produce a product that is secreted into the environment, nor is it’s gene product itself toxic. It would not produce anything that distrupt natural occurring symbiosis.
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<p style="text-align: justify;">The BioBrick does not produce a product that is secreted into the environment, nor is it’s gene product itself toxic. It would not produce anything that distrupt natural occurring symbiosis.</p>
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The BioBrick might increase a bacteria’s ability to find nutrients and as such ease its ability to replicate and spread in certain dark environments. On the other hand the BioBrick is very large and this will naturally slow down its replication rate. Generally we do not believe this BioBrick will make its host able to outcompete natural occurring bacteria, simply because it’s function is not something that will give its host a functional advantage.   
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<p style="text-align: justify;">The BioBrick might increase a bacteria’s ability to find nutrients and as such ease its ability to replicate and spread in certain dark environments. On the other hand the BioBrick is very large and this will naturally slow down its replication rate. Generally we do not believe this BioBrick will make its host able to outcompete natural occurring bacteria, simply because it’s function is not something that will give its host a functional advantage.  </p>
====Possible malign use====
====Possible malign use====
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This BioBrick will not increase it’s hosts ability to survive in storage conditions, to be arosoled, to be vaporized or create spores. None of its proteins regulate or affect the immune system or are pathogenic towards humans and animals.
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<p style="text-align: justify;">This BioBrick will not increase it’s hosts ability to survive in storage conditions, to be arosoled, to be vaporized or create spores. None of its proteins regulate or affect the immune system or are pathogenic towards humans and animals.</p>
===References===
===References===
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# Spiegl N, Didichenko S, McCaffery P, Langen H, Dahinden CA. [http://www.ncbi.nlm.nih.gov/pubmed Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid]. Blood. 2008 Nov 1;112(9):3762-71.
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<p style="text-align: justify;"># Spiegl N, Didichenko S, McCaffery P, Langen H, Dahinden CA. [http://www.ncbi.nlm.nih.gov/pubmed Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid]. Blood. 2008 Nov 1;112(9):3762-71.
# Russell RM. [http://www.ncbi.nlm.nih.gov/pubmed/10731492 The vitamin A spectrum: from deficiency to toxicity]. American Journal of Clinical Nutrition, Vol. 71, No. 4, 878-884, April 2000.
# Russell RM. [http://www.ncbi.nlm.nih.gov/pubmed/10731492 The vitamin A spectrum: from deficiency to toxicity]. American Journal of Clinical Nutrition, Vol. 71, No. 4, 878-884, April 2000.
# Pasquali D, Thaller C, Eichele G. [http://www.ncbi.nlm.nih.gov/pubmed/8964849 Abnormal level of retinoic acid in prostate cancer tissues]. J Clin Endocrinol Metab. 1996 Jun;81(6):2186-91.  
# Pasquali D, Thaller C, Eichele G. [http://www.ncbi.nlm.nih.gov/pubmed/8964849 Abnormal level of retinoic acid in prostate cancer tissues]. J Clin Endocrinol Metab. 1996 Jun;81(6):2186-91.  
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# Mennes N, Klare JP, Chizhov I, Seidel R, Schlesinger R, Engelhard M. [http://www.ncbi.nlm.nih.gov/pubmed Expression of the halobacterial transducer protein HtrII from Natronomonas pharaonis in Escherichia coli.] FEBS Lett. 2007 Apr 3;581(7):1487-1494.  
# Mennes N, Klare JP, Chizhov I, Seidel R, Schlesinger R, Engelhard M. [http://www.ncbi.nlm.nih.gov/pubmed Expression of the halobacterial transducer protein HtrII from Natronomonas pharaonis in Escherichia coli.] FEBS Lett. 2007 Apr 3;581(7):1487-1494.  
# Oxley APA, Lanfranconi MP, Würdemann D, Ott S, Schreiber S, McGenity TJ, et al. [http://www.ncbi.nlm.nih.gov/pubmed Halophilic archaea in the human intestinal mucosa]. Environ Microbiol [Internet]. 2010 Apr 23 [cited 2010 Oct 26].
# Oxley APA, Lanfranconi MP, Würdemann D, Ott S, Schreiber S, McGenity TJ, et al. [http://www.ncbi.nlm.nih.gov/pubmed Halophilic archaea in the human intestinal mucosa]. Environ Microbiol [Internet]. 2010 Apr 23 [cited 2010 Oct 26].
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Revision as of 11:40, 26 October 2010