Team:Virginia

From 2013.igem.org

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<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Although minicells fail to cause infection because of their inability to replicate, recognition of the LPS and surface proteins by the human immune system may lead to septic shock. To prevent any such possibility, a weakened bacteria strain, IpxM, expressing Ail protein and polysialic acid will be used. Expressed on the cell surface, Ail avoids deposition in human serum while polysialic acid prevents activation of the complement system. By coupling these precautions with their inherent safety, minicells provide a safe, targeted chassis which may be employed in future synthetic biology research.
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<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Although minicells fail to cause infection because of their inability to replicate, recognition of the LPS and surface proteins by the human immune system may lead to septic shock. To prevent such an occurrence, a weakened bacterial strain (IpxM) expressing Ail protein and polysialic acid will be used. Expressed on the cell surface, Ail helps bacteria avoid complement deposition in human serum, while polysialic acid also prevents the activation of the complement system. By coupling these precautions with their inherent safety, minicells provide a safe, targeted chassis which may be employed in future synthetic biology research.
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<h6><b>Sources</b></h6>
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<h6>Anisimov, A., Shalkhutdinova, R., Pan, L., Feodorova, V., Savostina, E., Bystrova, O., Lindner, B., & Mokrievich, A. (2007). Effect of deletion of the lpxm gene on virulence and vaccine potential of yersinia pestis in mice. Journal of Medical Microbiology, 56(4), 443-53. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17374882?dopt=AbstractPlus </h6>
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<h6>Frazer, A. & Curtiss, 3rd R. (1975). Production, properties and utility of bacterial minicells. Current Topics in Microbiology and Immunology. 69, 1–84.</h6>
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<h6>Kolodziejek, A., Schnider, D., Rohde, H., Wojtowicz, A., Bohach, G., Minnich, S., & Hovde, C. (2010). Outer membrane protein x (ail) contributes to yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length. Infectious Immunology, 78(12), 5233-43. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20837715</h6>
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<h6>MacDiarmid, J. A., Mugridge, N. B., Weiss, J. C., et al. (2007). Bacterially derived 400 nm particles for encapsulation and cancer cells targeting of chemotherapeutics. Cancer Cell, 11(5), 431-45. </h6>
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<h6>Ward, J.E., Lutkenhaus, J. (1985). Overproduction of FtsZ induces minicell formation in Escherichia-coli. Cell, 42(3), 941-9.
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Revision as of 17:17, 9 August 2013

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Home Team Official Team Profile Project Human Practices Parts Submitted to the Registry Modeling Notebook Safety Attributions

Preliminary Description:

     Safety remains a serious issue in synthetic biology; in particular, the development of drug delivery via targeted, live bacteria presents significant concern. Minicells provide a safe alternative to live bacteria while still retaining many of the features that make the latter such a promising potential chassis.

     Minicells result from aberrant cell division leaving one of the daughter cells significantly smaller (typically ~400 nm) and without chromosomal DNA; consequently, minicells are unable to replicate or cause infection. As then maintain the parent cell’s physical characteristics, including proton gradients, surface proteins, and plasmid DNA, minicells serve as an ideal chassis for receptor-targeted drug delivery.

     We plan to create a standardized BioBrick for the creation of E. coli minicells through IPTG induction of FtsZ, a gene which causes aberrant cell division when overexpressed. Our modeling efforts focus on identifying the most efficient level of such IPTG induction.

     Although minicells fail to cause infection because of their inability to replicate, recognition of the LPS and surface proteins by the human immune system may lead to septic shock. To prevent such an occurrence, a weakened bacterial strain (IpxM) expressing Ail protein and polysialic acid will be used. Expressed on the cell surface, Ail helps bacteria avoid complement deposition in human serum, while polysialic acid also prevents the activation of the complement system. By coupling these precautions with their inherent safety, minicells provide a safe, targeted chassis which may be employed in future synthetic biology research.

Sources
Anisimov, A., Shalkhutdinova, R., Pan, L., Feodorova, V., Savostina, E., Bystrova, O., Lindner, B., & Mokrievich, A. (2007). Effect of deletion of the lpxm gene on virulence and vaccine potential of yersinia pestis in mice. Journal of Medical Microbiology, 56(4), 443-53. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17374882?dopt=AbstractPlus
Frazer, A. & Curtiss, 3rd R. (1975). Production, properties and utility of bacterial minicells. Current Topics in Microbiology and Immunology. 69, 1–84.
Kolodziejek, A., Schnider, D., Rohde, H., Wojtowicz, A., Bohach, G., Minnich, S., & Hovde, C. (2010). Outer membrane protein x (ail) contributes to yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length. Infectious Immunology, 78(12), 5233-43. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20837715
MacDiarmid, J. A., Mugridge, N. B., Weiss, J. C., et al. (2007). Bacterially derived 400 nm particles for encapsulation and cancer cells targeting of chemotherapeutics. Cancer Cell, 11(5), 431-45.
Ward, J.E., Lutkenhaus, J. (1985). Overproduction of FtsZ induces minicell formation in Escherichia-coli. Cell, 42(3), 941-9.


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