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Our major contribution to future iGEM teams in general is the characterization of the steroid biosynthesis pathway, and an in-depth literature collection that contains everything a future team should need to know to become an expert on yeast steroid biosynthesis pathways.
We originally discovered the possibilities inherent in this pathway and our biobricks when we saw it described on the UCSC 2018 PoPPY project short for “Portable Progesterone Production in Yeast” where the enzymes were expressed in the oleaginous yeast Yarrowia Lipidica. They designed their yeast to produce progesterone, a hormone for birth control. Focusing on personal biomanufacturing to provide access to family planning in the developing world, they combined their pathway with a riboswitch to control the percentage of progesterone that would be produced in fermentation.
This was a major inspiration for our project and shows the versatility of these enzymes and their applications in yeast. We chose to focus on the fundamental proof of concept for advanced steroid fermentation, testosterone, which requires the addition of several more enzymatic steps past this point. We also chose to include enzymes, in conjugation with knockout strains, that would target the production of cholesterol in order to compare the effects on downstream steroid production to the processes described in their project and in literature. When deciding on the end users of our process, we decided early in the project that we could not plan to distribute publicly, as they did, for a number of reasons. Chief among them, and something that all future users of these bricks should be aware of, is that Testosterone is a controlled substance in most of the world. Due to its uses by athletes in “doping” or by bodybuilders there is an active black market for anabolic steroids and researchers should be very careful how they develop and distribute their strains. (If you would like to know more about Testosterone and its applications please see the Testosterone section of the Project Description)
Further, our research and analysis shows that the products of our process will be far from “pure.” A varied combination of yeast biomolecules, sterols, and steroids will be the result of a fermentation with these bricks unless large amounts of engineering is done to correct this. Even then, interviews with experts stress that purification should be done by professionals, to reduce the risk of injury and even death. (If you would like to know more about our process please see the Biomanufacturing section of the Project Description)
Additionally, since personal production of testosterone is likely not legally possible, commercialization with either a for-profit or non-profit manufacturer will be a necessity. This means that you will have to deal with intellectual property rights. While our research shows that due to the long dormancy of this research, several of the key patents (which can be found in our results section) have lapsed or will lapse in several countries. HormOWN has reached out to several patent experts and IP Attorneys over the course of our process (details can be found in Human Practices and IP section of the Project Description) and has plans to pursue “Open-Sourcing'' of this pathway to allow free use or permissive licensing in the future. We see this as integral to our mission of improving access, decreasing the costs, and fighting shortages of essential generic steroidal medicines. However, the legal landscape will be tricky, and can be more so for transparent non-profits. “Patent thickets” can extend the lifespan of a monopoly almost indefinitely and “IP Trolls” can sue you with the thinnest of justifications. We recommend caution to future researchers attempting to commercialize this process.
With these disclaimers out of the way, we would like to highlight the tremendous potential of these biobricks. As we have stated before, steroid molecules are the basis for a $10 billion dollar global industry and are the second largest class of drugs after antibiotics. The potential for iGEMers and Biotechnologists to do good in the world does not end with this project. With over 300 approved steroidal drugs and a mountain of process optimization we look forward to seeing how these bricks can change the world.
Participating in iGEM is an overwhelming experience by itself, however, I believe that being team leader and project manager in the context of iGEM is a different beast. As a team leader and project manager of BOKU-Vienna in 2022, I can attest that this role was a thrilling rollercoaster, filled with its unique blend of challenges and rewards. While every year comes with its special set of circumstances, some universal lessons can be learned from each experience.
Our team was quite small. In a small team, every member's contribution is essential, and there's no room for slack. However, when team members are stretched thin with work commitments and exam preparation, maintaining a consistent workflow becomes a daily puzzle. Scheduling meetings, coordinating experiments, and ensuring everyone's on the same page requires meticulous planning and flexibility, and this responsibility falls squarely on the team leader.
For Future Team Leaders:
Taking on an ambitious iGEM project with constrained resources is like attempting a marathon with a pair of worn-out sneakers. Lacking funds and manpower was a big roadblock we had to tackle at every point during the competition. We've had to adapt and get creative, sometimes simplifying our project's scope to align with our available resources.
For Future Team Leaders:
The pressure of exams, work, and iGEM can lead to burnout and emotional stress. Maintaining team morale and ensuring everyone's well-being is an ongoing challenge, and as a team leader, the responsibility is on you. Finding the right balance between pushing ourselves to excel and taking breaks to recharge is crucial.
For Future Team Leaders:
The iGEM experience was draining in many ways, but it was also an effective teaching tool for me as a team leader – in such a high-pressure environment, one must learn to wear many hats as a leader, and to wear those hats with pride, competence, and determination. Whenever some of my team members asked me how I was doing, I always answered in the same way: “Diamonds are made under pressure.”, followed by a resigned sigh or a dry laugh. While many team leaders, reading this, may agree with this sentiment, I can only offer one more thing to think about: Diamonds, too, need some rest.