Team:UofC Calgary/Description
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 to 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.
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.
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.
