Difference between revisions of "Team:UofC Calgary"

 
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<a href="https://2016.igem.org/Team:UofC_Calgary/project/solution">Our Solution</a>
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<a href="https://2016.igem.org/Team:UofC_Calgary/HP/Gold">Gold</a>
 
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                                    <a href="https://2016.igem.org/Team:UofC_Calgary/Policy"> Policy Brief </a>
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                                            <p style="color: #FFFFFF">We are honoured to announce that the UofC_Calgary 2016 iGEM was incredibly successful at this year's iGEM Giant Jamboree. We received a <u>gold medal</u>, a nomination for <u>Best Applied Design</u>, and the award for <u>Best Integrated Human Practices</u>! We are beyond thrilled to continue the University of Calgary's tradition of excellence at iGEM, and extend our deepest gratitude to those who aided us in any form during this journey.
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</p><div class="col-md-4"><center><img src="https://static.igem.org/mediawiki/2016/a/a3/T--UofC_Calgary--Gold%28%2B%29.png" style="width:20vw;" alt="Gold Medal didn't load. Please Refresh Page."></center></div><div class="col-md-8" style="padding-top: 50px;"><center> <img width="500px" height="375px" src="https://static.igem.org/mediawiki/2016/5/5a/T--UofC_Calgary--boston_photo.jpg"></center>
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                                             <p style="color: #FFFFFF">Mars and the cosmos are a tantalizingly close goal for Mankind to reach in the next century; however, there are several glaring problems that we must overcome to reach such an objective. Radiation is chief among them. On Earth, individuals annually receive 2.4 mSv of ionizing radiation (IR), which is easily tolerated by the human body. Unfortunately, without the protection of the magnetosphere, astronauts in space are exposed to high levels of IR in the range of 50 to 2000 mSv. This level of radiation causes the accumulation of deleterious double strand breaks in DNA. Despite current research into methods of IR protection, many solutions such as radiation shield coating are quite expensive, especially to transport to space. Even existing biological solutions are insufficient, such as the use of ingestible or injectable radioprotectors, which are subject to sinusuoidal pharmacokinetics. Our project is based on the administration of the naturally occuring peptide Bowman-Birk Protease Inhibitor (BBI), which has been shown to confer protection against DNA damage following radiation exposure. (Dittmann <i>et al.</i>, 2003). </p>
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<p style="color: #FFFFFF">References</p>
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<p style="color: #FFFFFF"><font size="2">Dittmann, K.H., Mayer, C., and Rodemann, H.P. (2003). Radioprotection of normal tissue to improve radiotherapy: the effect of the Bowman Birk protease inhibitor. <i>Current Medicinal Chemistry - Anticancer Agents, 3</i>(5), 360-363.</font </p>
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                                             <p style="color: #FFFFFF">Mars and the cosmos are tantalizingly close for Mankind to reach in the next century; however, there are several glaring problems that we must hurdle to reach this objective. Stellar radiation is chief among them. Each year on Earth, individuals receive 2.4 mSv of ionizing radiation (IR), which is easily tolerated by our cells. In space without the protection of the magnetosphere, astronauts are exposed to high levels of IR in the range of 50 to 2000 mSv which causes the accumulation of deleterious double strand breaks in DNA. Despite current research into methods of IR protection, many solutions such as radiation shield coating are expensive especially to transport to space. </p> <p style="color: #FFFFFF">
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Biological solutions such as the use of radioprotectors are also subjected to the sinusoidal pharmacokinetic problem resulting in the need for constant administration and the accumulation of waste. Certain naturally-occurring proteins and peptides, such as the modified Bowman-Birk Inhibitor (mBBI), have been found to confer protection against DNA damage in cells exposed to ionizing radiation. Previous studies have shown that BBI increases the survival rate of cells significantly when irradiated, by augmenting endogenous DNA repair mechanisms.
 
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To solve the problem of creating a cost effective and continuous delivery system for IR protection, we have designed a transdermal patch for the delivery of mBBI through the skin. The patch hosts recombinant <i>Bacillus subtilis</i> that expresses a mBBI gene tagged with a transdermal tag that allows the peptide to travel through the skin layers, and into the bloodstream for dispersal throughout the body. The recombinant protein is also tagged with a secretory tag, which is cleaved off using endogenous proteases before delivery out to the skin. Using B. subtilis for the production of mBBI allows for constant delivery bypassing the sinusoidal pharmacokinetic problem. Its long term, continuous delivery will also create a cost effective solution. Ultimately our transdermal delivery system allows for the administration biotherapeutics within an efficient and practical system, while still maintaining the flexibility of modularity.
 
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                                            <p style="color: #273236">To express mBBI, we had to choose a biological system that was not only capable of high expression but was robust, adaptable, and easily genetically manipulated for ease of transport and use in remote and extreme environments. After creating a list of different types of cells which could be used for the expression of our peptide, we found that <i>Bacillus subtilis</i> was especially suited for our patch design. This is due to many reasons. <i>B. subtilis</i> is able to express high amounts of recombinant protein which can be secreted into surrounding media by its own well-characterized secretion system, making it ideal for producing and delivering the correct dosage of mBBI into the user. <i>B. subtilis</i> is capable of forming spores—which have been found in arctic permafrost dating tens of thousands of years and yet are still viable—making it easy to store in a desiccated or frozen manner. Additionally, <i>B. subtilis</i> expresses high amounts of recombinase A, a protein which allows genes to be stably integrated into the chromosome.</p>
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<p style="color: #273236">Our strain of <i>B. subtilis</i> (WB800) is particularly suited for high production because it is deficient in eight extracellular proteases which could lead to the premature degradation our radioprotective peptide. Our strain will allow the peptide to be stable in the media within the patch. We conducted tests on the growth patterns of <i>B. subtilis</i> in the novel environment of a patch and optimized patch media to simulate an ideal growth conditions. We have also designed a genetic construct which provides inducible competency to the <i>B. subtilis</i> strain upon the addition of xylose, making this bacterium much easier to work with for future teams. </p>  
 
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The 2016 U of C Calgary iGEM team is a multidisciplinary team based out of the University of Calgary. Our team is made up of undergraduate students from all years of study, hailing from the broad backgrounds of biology, microbiology, biomedical sciences, bioinformatics, and engineering. We are based out of the O'Brien Centre Labs within the U of C's Health Science Centre.  
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Our entire team received a full BioSafety education from the University of Calgary! This entailed going to classes to prepare for a final quiz that tested our ability to be safe in the lab. Several of our members also had radiation training and clearance to ensure that work done with radiation was safe!
 
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Latest revision as of 20:38, 2 December 2016

iGEM Calgary 2016

Giant Jamboree Results

We are honoured to announce that the UofC_Calgary 2016 iGEM was incredibly successful at this year's iGEM Giant Jamboree. We received a gold medal, a nomination for Best Applied Design, and the award for Best Integrated Human Practices! We are beyond thrilled to continue the University of Calgary's tradition of excellence at iGEM, and extend our deepest gratitude to those who aided us in any form during this journey.

Gold Medal didn't load. Please Refresh Page.

Our Project

Mars and the cosmos are a tantalizingly close goal for Mankind to reach in the next century; however, there are several glaring problems that we must overcome to reach such an objective. Radiation is chief among them. On Earth, individuals annually receive 2.4 mSv of ionizing radiation (IR), which is easily tolerated by the human body. Unfortunately, without the protection of the magnetosphere, astronauts in space are exposed to high levels of IR in the range of 50 to 2000 mSv. This level of radiation causes the accumulation of deleterious double strand breaks in DNA. Despite current research into methods of IR protection, many solutions such as radiation shield coating are quite expensive, especially to transport to space. Even existing biological solutions are insufficient, such as the use of ingestible or injectable radioprotectors, which are subject to sinusuoidal pharmacokinetics. Our project is based on the administration of the naturally occuring peptide Bowman-Birk Protease Inhibitor (BBI), which has been shown to confer protection against DNA damage following radiation exposure. (Dittmann et al., 2003).

References

Dittmann, K.H., Mayer, C., and Rodemann, H.P. (2003). Radioprotection of normal tissue to improve radiotherapy: the effect of the Bowman Birk protease inhibitor. Current Medicinal Chemistry - Anticancer Agents, 3(5), 360-363.

OUR CHASSIS

To express mBBI, we had to choose a biological system that was not only capable of high expression but was robust, adaptable, and easily genetically manipulated for ease of transport and use in remote and extreme environments. After creating a list of different types of cells which could be used for the expression of our peptide, we found that Bacillus subtilis was especially suited for our patch design. This is due to many reasons. B. subtilis is able to express high amounts of recombinant protein which can be secreted into surrounding media by its own well-characterized secretion system, making it ideal for producing and delivering the correct dosage of mBBI into the user. B. subtilis is capable of forming spores—which have been found in arctic permafrost dating tens of thousands of years and yet are still viable—making it easy to store in a desiccated or frozen manner. Additionally, B. subtilis expresses high amounts of recombinase A, a protein which allows genes to be stably integrated into the chromosome.

Our strain of B. subtilis (WB800) is particularly suited for high production because it is deficient in eight extracellular proteases which could lead to the premature degradation our radioprotective peptide. Our strain will allow the peptide to be stable in the media within the patch. We conducted tests on the growth patterns of B. subtilis in the novel environment of a patch and optimized patch media to simulate an ideal growth conditions. We have also designed a genetic construct which provides inducible competency to the B. subtilis strain upon the addition of xylose, making this bacterium much easier to work with for future teams.

Design Overview






We designed our project to overcome common issues in existing technologies such as cost, portability, and durability. Our patch is portable, lightweight, safe to use, can be stored long-term, and produces and delivers peptides at a steady rate to maintain a constant concentration in the body. We worked with professionals within NASA and the CSA to integrate our solution with current space travel infrastructure, and with companies specializing in transdermal delivery to optimize the patch system. We also consulted with professionals and researchers in biomedical fields to better understand the unknown effects our delivery system would have when in use. Using this system, our project has future applications here on Earth for other occupations and individuals exposed to high levels of ionizing radiation, such as pilots, flight attendants, and miners. Our project can also be used to deliver hormones and other small molecules for use in space, serving as a "biological pharmacy."










Our Project

Project Description

Our Experiments

Modelling

Human Practices

Click to learn more about each part of our project

About us

The 2016 U of C Calgary iGEM team is a multidisciplinary team based out of the University of Calgary. Our team is made up of undergraduate students from all years of study, hailing from the broad backgrounds of biology, microbiology, biomedical sciences, bioinformatics, and engineering. We are based out of the O'Brien Centre Labs within the U of C's Health Science Centre.

Our Sponsors

iGEM

iGEM is an international competition promoting synthetic biology as a means to solve social, economic and humanitarian problems around the globe. The iGEM Jamboree is held in Boston annually. In 2016, over 300 teams are competing against each other.

Latest Entries

Fully Trained!

Our entire team received a full BioSafety education from the University of Calgary! This entailed going to classes to prepare for a final quiz that tested our ability to be safe in the lab. Several of our members also had radiation training and clearance to ensure that work done with radiation was safe!

Read More

Latest Pictures

View More

Find us

Located in Calgary, Alberta, Canada.

  • University of Calgary
  • igem.calgary@gmail.com

Copyright © University of Calgary 2016.