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Our solution strategy
With the recent advances that established a strong relationship between the human microbiome and human health and disease, new frontiers in synthetic biology have begun to emerge concomitantly. Namely, rather than engineering a single bacterium chassis as is normally done in conventional synthetic biology applications, we have opted to devise an engineering strategy for a microbiome in order to address health-related problems.
A national research program of the human microbiome has been established in the United States - The Human Microbiome Project (HMP). The goal of the HMP is to demonstrate that there are opportunities to improve human health through monitoring and/or manipulation of the human microbiome 10. New and promising startups have been established based on the idea of the utilization and adaptation of the human microbiome to our needs. For example, AOBiome, LLC. created a dedicated line of products (named ‘Motherdirt’) - the first line of products for the skin made, which includes live bacteria incorporated into the product itself (Ammonia Oxidizing Bacteria) 11. This product was publicized extensively in the media - In “The New York Times” and “Good Morning America”. In the past several years, several other big cosmetic companies have released products incorporating natural bacteria - “Clinique Redness Solutions Makeup SPF 15” by Clinique and “Cosmeceuticals Unstress Total Serenity Serums” by Christina are few examples of this promising market 12.
Using this trend in research and cosmetics, we decided to develop a new synthetic biology approach for engineering a microbiome. In our approach, we opt to genetically alter one or more of the bacterial populations that are naturally present to secrete a particular enzyme. Thus, on the one hand we minimally perturb the natural microbiome, while on the other we co-opt it to produce a sustainable treatment of some sort.
We decided to apply this approach on the problem of male pattern baldness. We planned to alter the most abundant bacterium which is naturally found on our scalp (Bacillus subtilis) 15 and genetically engineer it for our needs: taking advantage of its natural protein secretion pathways in order to secrete a DHT-reducing enzyme (as will be explained in the following paragraph). This new application of the human microbiome usage is a path, in our opinion, to solve a variety of conditions and enhance overall wellness in the future.
Solution
The proposed solution is to incorporate the gene of a DHT-inactivating enzyme into a bacterium that is naturally found on our scalp (B.subtillis). These transgenic microorganisms will be applied on the patient's scalp, and will secrete the enzyme to their environment, providing a constantly renewed supply of the treatment. The proposed DHT-inactivating enzyme is the 3α-hydroxysteroid dehydrogenase (3α-HSD) enzyme. DHT is inactivated by the 3α-HSD to form 3α-androstanediol 13, as shown in figure 1 below.
Figure 1:Androgen metabolism in the human prostate13
3α-HSD exists naturally in human prostate, performing the mentioned reaction14. However, according to previous research, the isoform originated from rat liver has greater specificity to DHT than the human isoform 16. Therefore, we chose to use the sequence of AKR1C9 for our project. We altered the sequence in order to delete forbidden restriction sites according to the iGEM regulations for BioBricks.
The components of the project
An illustration of our proposed solution and project components can be seen in Figure 2.
Figure 2: Schematic illustration of the project design, incorporating its main components: Bacillus subtilis (illustrated by the blue bacteria) which secretes 3α-HSD (illustrated by the yellow circles), engineered E.coli (illustrated by the red bacteria) for NADPH molecule (illustrated by the green circles) overproduction, and a comb as a tool to create a user-friendly experience.
In order to better focus on the many different components of our project, we split up into groups to tackle each component: Expression of the 3α-HSD enzyme, secretion of the enzyme, and cofactor production. Additionally, a group worked on developing a comb- a tool which could provide a user-friendly solution for the consumer in applying our product to the scalp. For more information about each sub-group, enter the page from the menu above, or visit the links below:
Secretion
Expression
Cofactor
Comb and Design
Results
Modeling
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