Team:Virginia/Human Practices
Index:
Integrated Human Practices
How We Began
Beginning our project in the midst of a pandemic, we knew we needed to refocus our time outside the lab to learn as much as we could about the market space our planned device would occupy, as well our greater role in the Synthetic Biology community. Below we have detailed the experts we spoke to for the many facets of our project, and how they led us to refine our goals and reach our final products. There isn't a linear path that details the work we did, but in every field we found interest, we focused on talking to the right people in the pursuit of a better product.
Building a Basis
Our first goal for outreach was to understand our responsibilities as a team in the synbio community, and what part we can play in pursuit of good practice. Early on, we reached out to
Dr. Lois ShepherdLois Shepherd, Bioethics Professor, UVA School of Law
, a UVA bioethicist, to gain insights into the pharmaceutical manufacturing industry. We were looking for basic information on good practice in biology and how to fulfill our duties as scientists beyond just safety forms and university guidelines. Dr. Shepherd advised us to assess how we can actually benefit society despite the restrictions of patent monopolies, and suggested we write a Code of Ethical Conduct (COEC) to organize our findings. She stressed important questions regarding what we wanted to accomplish with our project, who it would affect, and how we could balance benefits, risks, and harms. Dr. Shepherd then pointed us to Professor Riley, a fellow UVA Bioethicist, for advice more specific to synthetic biology.
Armed with new relevant questions and our own tentative answers, we reached out to
Mimi RileyMimi Riley, Professor of Law and Public Health Sciences, UVA School of Medicine
, a professor of law at UVA, as well as a legal advisor to the Health Sciences Institutional Review Board. In our first meeting, we asked general questions regarding synthetic biology in society, and our conversations gradually shifted to discussing the current social movements occurring in the country and whether we have a role as a research team to take a stance on such issues. We spoke at length about our capability to positively impact our community, as well as the difficulty of going beyond merely making a statement. Professor Riley endorsed the idea of our COEC as a means to debate and cement our values as a team and how they affect the work we put out into society. Our COEC also gives us guidelines for how we as a team utilize Manifold, and the values we would hold companies to if our technology was licensed out. In Figure 1, you can see the introduction to our COEC, which states our intention to maximize good and mitigate risks, with guidelins detailed later in the Code. Professor Riley met with us again to review our COEC draft and gave us advice on individual statements and sections, and how to finalize this document for others to adopt and improve. Our COEC is a framework that we hope other teams can adopt, adapt, and utilize in the future. Its genesis took a lot of internal discussion, but without the guidance of Dr. Shepherd and Professor Riley, we would not have understood the true importance of the work we were doing. If you would like to view our Code of Ethical Conduct, please view our Public Engagement tab.
Fig 1. The introduction to our Code of Ethical Conduct, stating our goals for the document and our hope that other teams can use this framework to document their own efforts and considerations.
A Page For iGEM, by iGEM
Moving forward after our COEC, we sought to reflect on team adaptations to the global pandemic in a meaningful manner. With all of the new virtual tools and workflows we had developed in order to optimize teamwork during unprecedented conditions, we sought a way to share not only our resources and learnings with other teams, but a way for teams around the world to share these amongst one another. This was especially meaningful in the context of iGEM, where cultural and geographical differences pose varying challenges to teams with respect to resource needs and access. With insightful feedback from the new iGEM Video and Remote Technology (VRT) committee, we were able to collect resources from other teams using Surveymonkey and share this collection of resources via our social media platforms. Figure 2 provides the introduction to the Resource Hub, and our intentions for the document. If you would like to see our Resource Hub, please see the Contributions page.
Fig 2. The introduction to our iGEM resource document, showing the seperation of resoruces as well as contact information to suggest new tools.
Registering our Patent
Our entrepreneurial efforts began with the intention to patent our device. The first step we took was reaching out to patent lawyers to get a better understanding of what steps we needed to take in order to registering our intellectual property (IP). We contacted
Nathan EvansNathan Evans, Intellectual Property and Patent Attorney, Woods Rogers
, a patent lawyer in the Charlottesville area who offered us a no-cost meeting to discuss the process of filing and how to protect ourselves from losing claim to our device. Mr. Evans detailed our path forward and the strict time frame that a patent application requires. We also consulted David VanceDavid Vance, Patent Attorney, Vance Intellectual Property
, another local patent attorney who was more focused on scientific and medical IP. Mr. Vance gave us more specific guidance and also described how groups of our nature make the decision to either work through the University or independently. He agreed to continually advise us up through our patent application submission, and he was instrumental in helping us navigate our provisional patent.
This patent work also required interaction with the UVA Licensing and Ventures Group (LVG). In our meeting with UVA LVG, we discussed how UVA’s investment in our project might be exchanged for partial ownership, and, more generally, how our university supports the entrepreneurial efforts of its students. We had many team discussions about the pros and cons of the resources the university could offer us and how we could foster the growth of our idea within our own university.
These early meetings cemented our interest in growing this project beyond the end of the iGEM competition. A team decision was made to create the Entrepreneurship committee, which explores our own finances and structure in order to potentially grow our device beyond the scope of a project. In the end, we submitted our provisional patent application and assembled market research in the biologics field to understand the market for resveratrol. For a more detailed explanation of our efforts here, check out our Entrepreneurship page.
Fig 3. Two of the figures that were submitted as part of the provisional patent application.
Growing a Business
Throughout discussions with the patent lawyers, we realized we had little information on how our product would be developed following the establishment of a patent. So, we scheduled a meeting with
Rahul KeshapRahul Keshap, Lecturer, UVA School of Law
, a lecturer in the UVA law school. He broke down each of our team's individual claims to the idea, and how we could best move forward in forming a company. With our Entrepreneurship committee in place, we began reaching out to those who work in biotech in our community. In this pursuit, we talked to Nicki HastingsNikki Hastings, Executive Director, Cville Biohub
, Executive Director of Cville Biohub, a Charlottesville collective of biological startups working to build their companies in the local incubator. From the start, we were interested in their business model and the other companies under the banner of Cville BioHub, and she was able to break down how companies utilize Cville Biohub to build their ideas, and what steps we could take to potentially work within the Biohub after the iGEM competition. We also received encouragement from Dr. Mark KesterMark Kester, Biomedical Engineering Professor, UVA School of Engineering, Director of the nanoSTAR Nanotechnology Institute at UVA.
. Dr. Kester is currently the Director of the nanoSTAR Nanotechnology Institute at UVA, and is assisting multiple past UVA iGEM teams as they work to bring their devices to market. His experience from helping our predecessors is invaluable, and he has provided us with lessons from past teams to aid in the development of Manfold.
Understanding the Components
Pivoting to wetlab, our first goal was to specify the bioengineering problem we wished to tackle. We also refined the design of our device as much as possible, and decided to consult some experts on the possible limitations of our device and how we would go about actually assembling the device as efficiently as possible. This largely involved us reaching out to researchers whose papers had been instrumental in conceiving the device.
We began by emailing
Dr. Cheryl KerfeldCheryl Kerfeld, Biochemistry Professor, Michigan State University
, a renowned researcher out of UCLA and Michigan State with a long history of experimenting with BMCs. Dr. Kerfeld agreed to talk about her cutting-edge BMC research, even explaining her current work on customizable, synthetic BMC shells, and also gave feedback on our initial project ideas. She immediately took to our concept, and afforded us the endorsement of a researcher who's worked with BMCs for decades. She also referred us to other BMC experts, including Dr. Martin Warren, and encouraged us to narrow down our design to fix smaller, more specific problems, rather than combating “metabolic flux leakage” as a whole.
Build Smarter, Not Harder
We also reached out to
Dr. Martin WarrenMartin Warren, Professor of Biochemistry, Kent University
from Canterbury, UK, after reading a paper of his. What began as a chance email with a couple clarifying questions about his work became a continued dialogue about his advancements with BMCs. He also agreed to share multiple plasmids and sequences described in his paper, giving us the ability to partially replicate his findings, and a much faster route to creating our final device. This was a tremendous success since our in-lab time had been reduced to just one month, so having tried and true plasmids being supplied to us was appreciated greatly.
Despite these resources, we still understood that there was an immense amount of wetlab work that needed to be done in a short period of time. Looking for other ways to streamline our lab approach, we spoke to
Dr. George McArthurFounder of Virginia iGEM, Head of Product at Ansa Biotechnologies, Inc
, the founder of the Virginia iGEM Team, former Director of Genetic Design-Build at Arzeda, and new Head of Product at Ansa Biotechnologies, Inc. We did a short presentation for him on the wetlab component of our project, and he gave us advice on next steps for the project: get funding, expand possible applications and marketing points for the device, and look into ways to get data without having access to our lab space. These points, particularly the advice on how to outsource lab work and simplify our process, were invaluable, and when we entered the lab just weeks after this meeting, we were prepped in full to carry out our wet lab work and get data.
Modeling Manifold
The first step in modeling was to decide what models were needed, and for that we consulted
Dr. Jason PapinJason Papin, Biomedical Engineering Professor, UVA
, one of our iGEM advisors and the backbone of our modeling efforts. After the formulation of our device, our talks with Dr. Papin helped us to understand the questions we needed to answer and what models would answer such questions. He encouraged us to simplify the problem at hand and consider developing a multi-scale model to better understand metabolic flux leakage of metabolic reactions in BMCs. Dr. Papin also shared with us his own research lab’s resources to help us understand our models and create better outputs for presentation. We continually utilized his expertise in order to gain insight into the relevance of our models, to form a clear picture of what we were trying to gain, and in turn, what we would have to create. Click here to see the modeling workflow and “model network.”
In our creation, we found that our team had limited coding experience, and as a result, we reached out to
Ryan TaylorRyan Taylor, 2018 iGEM Team Captain, University of Virginia
. Ryan was the captain of the 2018 Virginia iGEM team, and is now an ongoing resource in developing our Pore Calculator Model. His knowledge of MatLab provided us with the ability to refine our models to be as applicable as possible, and his weekly interactions with the modeling committee ensured we were always on track and tackling problems and bugs as efficiently as possible. Ryan largely helped to smooth the modeling pipeline as a whole and to build out the theoretical foundation behind pore diffusion calculator, and his continued support on iGEM teams at UVA is greatly appreciated.
Contributors
Fig 4. Thank you so much to everyone who gave their time and knowledge to help us craft Manifold.
