Team:UofC Calgary/Description
Project Description
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.
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).
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 Bacillus subtilis 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.
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.
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 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.
