Selecting the Gene

Initially, we planned to create a cocktail of enzymes that would break down components of sebum (triglyceride oils, wax, squalene, and metabolites of fat-producing cells). However, as a first year team, we decided that choosing one enzyme would be the most practical.

In the beginning, we chose to use lipase as the enzyme to eliminate the bacterial food source. Because sebum is composed of 57.5% triglycerides and fatty acids, we decided that lipase which breaks down triglycerides into free fatty acids would be the optimal protein. However, through further research, we learned that when lipase converts triglycerides to free fatty acids, it only exacerbates the inflammatory response. Free fatty acids increase clumping of bacteria, which in turn facilitates the colonization in the duct. When inflammatory mediators penetrate the skin, an inflammatory reaction is initiated. P. acnes lipase (GehA, glycerol-ester hydrolase A) is in fact a virulence factor involved in the pathogenesis of acne. In Shuichi Higaki’s research paper, Higaki asserts that a lipase inhibitor can help treat acne. We contemplated the idea of trying to find a lipase inhibitor; however, few of the inhibitors are proteins. We contemplated using vitamin A, but it proved too complicated with too little standardization of use in accordance to the iGEM registry. In another approach, we thought we could break down the fatty acids before they were absorbed into a cell. The challenge was that acne vulgaris is a multi-factorial disease.

While we had all of these possibilities, many were completely unfeasible and unrealistic to try to accomplish. In the end, we decided on Medium Chain Alcohol and Aldehyde dehydrogenase. See our final decision.