Difference between revisions of "Team:UofC Calgary/Description"

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<p>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. </p> <p>
Mars and the cosmos are tantalizingly close for Mankind to reach in the next century; however, there are several glaring problems that we must overcome to reach this objective. Stellar radiation is chief among them. On Earth, individuals annually 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>
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Biological solutions, such as the use of ingestible or injectable radioprotectors, are subject sinusoidal pharmacokinetics. The therapeutic is delivered once, and although it may be effective initially, it will be degraded over time by the body, dropping its efficiency rate. This results in the need of re-administration of a drug to increase its activity in the body, resembling a sinusoidal curve. Certain naturally-occurring proteins and peptides, such as the Bowman-Birk Protease Inhibitor (BBI), 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 after they are irradiated by augmenting endogenous DNA repair mechanisms (Dittmann <i>et al.</i>, 2003).
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<p>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 (Dittman et al., 2003). </p>
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To create a cost effective and continuous delivery system for IR protection during space travel, we have designed a transdermal patch for the delivery of a modified version of BBI (mBBI) through the skin. The patch hosts recombinant <i>Bacillus subtilis</i> cells that express mBBI with a transdermal tag that allows the peptide to travel through the layers of the skin and into the bloodstream for dispersal throughout the body. This recombinant protein is fused to a <i>B. subtilis</i>-specific secretory tag, which permits the peptide to be secreted into the growth medium. Using <i>B. subtilis</i> for the production of mBBI allows for constant delivery and resolves the issue of sinusoidal pharmacokinetics. This long term, continuous delivery is also cost effective and minimizes waste. Ultimately, our transdermal delivery patch allows for the administration biotherapeutics within an efficient and practical system, while maintaining the flexibility of modularity, as <i>B. subtilis</i> could be used to produce a multitude of various peptides or small molecules.
<p>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 <i>B. subtilis</i> 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.</p>
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Our team was excited about this project from when we were first introduced to the topic of radio-protection by Dr. Aaron Goodarzi. A senior team mentor, Alina Kunitskaya, is also intensely interested in the quest to put mankind on Mars. Based on these twin influences on our team, synthetic biology technologies in space seemed to be a great niche our team to explore. Research on current space travel technology ensued, and the seeds of our project became planted. In terms of radio-protection, our team realized that synthetic biology is a perfect fit for this problem required to travel the cosmos. </p>
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Our team was excited about this project right from when we were first introduced to the topic of radio-protection by Dr. Aaron Goodarzi. A senior team mentor, Alina Kunitskaya, wass also intensely interested in the quest to put mankind on Mars. Based on these twin influences, synthetic biology technologies in space seemed to be a great niche for our team to explore. The seeds of our project were planted, and research on current space travel technology ensued. In terms of radio-protection, our team realized that synthetic biology is a perfect solution for this problem of long-term travel through the cosmos. </p>
  
                                         <p> We began with the project by toying around with ideas on how to deliver peptides into the body in an efficient way that astronauts could use easily everyday. This idea gradually evolved into the patch, mBBI tagged with the transdermal tag and developing <i> B. subtilis </i> as a platform to secrete our chosen peptide. We divided up the work to be done by subgroup types, and our team began the work of realizing our goals.   
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                                         <p> We began with the project by toying around with ideas on how to deliver peptides into the body in an efficient way that astronauts could use easily everyday. This idea gradually evolved into a patch containing mBBI fused to a transdermal tag alongside the development of <i> B. subtilis </i> as a platform to secrete our chosen peptide. We divided up the work to be done by subgroup types, and our team began the work of realizing our goals.   
 
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Revision as of 16:04, 14 October 2016

iGEM Calgary 2016

Project Description

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.

Biological solutions, such as the use of ingestible or injectable radioprotectors, are subject sinusoidal pharmacokinetics. The therapeutic is delivered once, and although it may be effective initially, it will be degraded over time by the body, dropping its efficiency rate. This results in the need of re-administration of a drug to increase its activity in the body, resembling a sinusoidal curve. Certain naturally-occurring proteins and peptides, such as the Bowman-Birk Protease Inhibitor (BBI), 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 after they are irradiated by augmenting endogenous DNA repair mechanisms (Dittmann et al., 2003).

To create a cost effective and continuous delivery system for IR protection during space travel, we have designed a transdermal patch for the delivery of a modified version of BBI (mBBI) through the skin. The patch hosts recombinant Bacillus subtilis cells that express mBBI with a transdermal tag that allows the peptide to travel through the layers of the skin and into the bloodstream for dispersal throughout the body. This recombinant protein is fused to a B. subtilis-specific secretory tag, which permits the peptide to be secreted into the growth medium. Using B. subtilis for the production of mBBI allows for constant delivery and resolves the issue of sinusoidal pharmacokinetics. This long term, continuous delivery is also cost effective and minimizes waste. Ultimately, our transdermal delivery patch allows for the administration biotherapeutics within an efficient and practical system, while maintaining the flexibility of modularity, as B. subtilis could be used to produce a multitude of various peptides or small molecules.

Our team was excited about this project right from when we were first introduced to the topic of radio-protection by Dr. Aaron Goodarzi. A senior team mentor, Alina Kunitskaya, wass also intensely interested in the quest to put mankind on Mars. Based on these twin influences, synthetic biology technologies in space seemed to be a great niche for our team to explore. The seeds of our project were planted, and research on current space travel technology ensued. In terms of radio-protection, our team realized that synthetic biology is a perfect solution for this problem of long-term travel through the cosmos.

We began with the project by toying around with ideas on how to deliver peptides into the body in an efficient way that astronauts could use easily everyday. This idea gradually evolved into a patch containing mBBI fused to a transdermal tag alongside the development of B. subtilis as a platform to secrete our chosen peptide. We divided up the work to be done by subgroup types, and our team began the work of realizing our goals.

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.

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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!

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Located in Calgary, Alberta, Canada.

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