Human Practices

Overview

Our team used Human Practices as inspiration to think about the general field of synthetic biology and our project specifically outside of our lab environment. We thought about how our project could be useful to researchers and other iGEM teams, specifically those interested in evolutionary stability and biosynthesis. We also considered how our project could impact members of the general public. Monitoring cellular capacity and evolutionary stability is crucial data that can lead to more successful iGEM projects. Overall, our project can have a positive impact to allow synthetic biologists to do more cost and time effective research . Knowing whether or not a part is “burdensome” to its host helps researchers have a more educated hypothesis about the stability of their construct, instead of losing days, weeks, and perhaps even months of their time troubleshooting a part only to discover that it was never reliable in the first place. Companies that spend less time and money on their R&D could lower the price of their product. This could be especially useful for therapeutic and biosynthesis companies. A more affordable product can then be favorable to the consumer. This could help more effectively scale highly priced products and help them be more accessible.

While our project has a broad impact outside of iGEM, our project can also be useful to other iGEM teams and iGEM HQ. Our team transformed and monitored the burden of about 500 parts from the 2018 iGEM kit. We believe we that our data is representative of the entire kit because we used frequently used parts as well as parts of different types. The data for these parts can be useful to other iGEM teams to know which parts are burdensome or toxic to its host. Our project also serves as a quality control for iGEM. Knowing whither or not a part will decrease growth rate or have an impact on cellular capacity helps teams narrow down which parts they will use. This allows teams to spend less time troubleshooting parts that will not work. This will also be beneficial for teams who are creating new constructs and characterize their part as burdensome or not to the cell.

We also sought opportunities to engage with our campus's synthetic biology center and the public in Austin. These experiences and opinions allowed us to develop our project and its relations to the world in a more comprehensive manner. Some of our team members also had the opportunity to volunteer at a Building with Biology event at the Thinkery in Austin. Engaging with these communities whether it be learning from someone in the field or educating someone who knows nothing about synthetic biology helped us think about how our project and synthetic biology in general impacts a wide variety of people.

Dr. Brian Renda from Gingko Bioworks

Our team thinks that it is important to think about evolutionary stability of genetic constructs for a variety of reasons. First, detecting which parts are unstable will allow us to find ways to increase evolutionary stability and cellular capacity. This would be very useful for labs wanting to maintain high gene expression or function for a long period of time. Furthermore, this allows us to help scientists avoid wasting their time and resources with potentially unstable genetic constructs, allowing them to do more cost-effective research.

In order to help our understanding of the benefits of our assay, as well as learn how to best represent and explain our data, we spoke to experts within the synthetic biology field. We talked to Brian Renda from Ginkgo Bioworks, and our discussion focused on how to best explore measuring metabolic burden, why it might be useful and problems that he faces with evolutionary stability.
n summary, our feedback from Brian helped us think of the importance of evolution stability. It was insightful to receive feedback from someone to learn about the importance of metabolic burden and how to talk about and represent our data. “Often times in industry you seek to maximize production of a specific biosynthetic pathway to make your product of interest … Sometimes this can lead to needing to use a majority of the cell's protein synthesis capacity to maximize production. I've seen instances where a single protein in a pathway makes up >50% of a cell's total protein… Also just understanding how much burden a given construct has in a specific backbone is going to only give partially useful data - often times we actually care about how these constructs function in highly engineered strain backgrounds ... Usually the biggest issues we see for genetic stability in industry are around the production of toxic compounds or intermediates and not as much effect of just over-expressing constructs.” -Brian Renda

Feedback and insight from Brian about our project and metabolic burden has been very useful. Knowing who would think our assay is applicable to their research and would use it helps our team with integrating Human Practices into our project. Talking about our ideas and progress gave us the opportunity to receive very crucial feedback on how to communicate the idea of metabolic burden, our project and display our data.

2019 Synthetic Biology Day and Undergraduate Research Symposium at the University of Texas at Austin

Diya and Noor at SynBio day.

Alex and Jordan at SynBio day.

Angela and Ginny at SynBio day.

Our team had the opportunity to attend the annual SynBio Day at our University. We also presented at the Undergraduate Research Symposium on our campus. We learned from many experts in the field from our university as well as an opportunity to give a poster presentation. We received some feedback from Dr. Andrew Ellington, a professor of molecular biosciences. This feedback was an opportunity to hear others opinions and make adjustments to our project. Being able to present a poster and give a talk allowed us to see the diversity of the field of Synthetic Biology as well as receive feedback and critique about our poster, presentation skills and our project ideas. We were also able to share with students and faculty about what iGEM is and how it is important for undergraduates to have more independent undergraduate research opportunities.

The Thinkery: Building with Biology

One of the ways in which some of our iGEM team members engaged with the public was through participating in Thinkery’s Building with Biology event. The Thinkery is a Austin located, STEAM-centered organization striving to enrich various educational opportunities to both children and their families via the implementation of hands-on learning experiences. Furthermore, Thinkery’s mission is to “create innovative learning experiences that equip and inspire the next generation of creative problem solvers,” which aligns well with iGEM’s core facets of education (through hands-on experiences as well as collaboration) and community (wherein the foundations for working together and mentoring are stressed between both organizations). Our team’s involvement with Thinkery’s Building with Biology event allowed us to pursue a deeper interaction with the general public outside of an academic atmosphere.

By being involved with the community in Austin, our team was able to interact with people from all sorts of skill and knowledge levels. From adults whom had already heard of synthetic biology to some degree to children whom had very little idea about synthetic biology, our team was able to get engaged and teach others about not only iGEM , but synthetic biology as a whole and how it could affect them in a way that reaches outside of the laboratory level. The extent at how this topic was discussed varied from individual to individual. With children, our team mostly worked on teaching them about synthetic biology in a simple and fun way for them to understand and potentially gain an interest in. For adults, our team mostly answered their questions about synthetic biology and talked to them about iGEM, and how it provided educational opportunities in STEM studies and fields of research. Our team emphasized the way in which working on iGEM helps provide an experience in working within a laboratory setting as well as expanding one’s own knowledge.

UT Natural Science Week: Painting With Bacteria

We interacted with students and staff about our project at the Painting With Bacteria event during UT Natural Science week. In this event, people had the opportunity to”paint” on petri dishes with E.Coli transformed with different colored chromoproteins. We introduced the idea of metabolic burden by showing people some colorless colonies that had appeared on chromoprotein plates that had been streaked out previously. We explained how some of the cells had stopped producing the chromoprotein because it was too much of a burden on the cell and a mutation in the chromprotein construct resulted in a survival advantage. We also talked about why it is important in the synthetic biology industry that we understand and quantify the metabolic burden of particular constructs, and exemplified this by talking about biosensors and indicators. We were able to talk to David Vanden Bout, the Senior Associate Dean and professor in the College of Natural Sciences at UT about the applications of cellular capacity outside of the lab. We asked him about what he knew about metabolic burden, and he responded by talking about how in processes where cells are producing a useful substance, it is important that the cells can continuously manufacture the substance over time. Furthermore, we also met a UT graduate student who’s research on plant cells utilized the concept of metabolic burden. We talked about how it is important to understand the burden on a microbiological level, and emphasized the value of communicating research to the public. Overall, the event was interesting and informative, and we were able to meet people with different backgrounds and explain the concepts behind our project while seeing their perspectives of the ideas.

Impact on Future iGEM Teams

In order to more effectively standardize our measurements and help the iGEM community, an application of our project would be to standardize a burden measurement for every part the iGEM registry. This would be done by transforming all functioning parts of the iGEM registry into our host strain and running them through our assay. This could even be something carried out by iGEM HQ labs. In order to test reproducibility it could be helpful for multiple iGEM teams to do this while also working on their own projects or even having a whole collaborative iGEM project.

The data collected by this “iGEM wide” burden monitor project would be very useful to iGEM teams and Synthetic Biologists. Specifically those who are interested in expressing a construct that carries out a function for biosynthesis or a biosensor. Because researchers often want higher expression or function it is very useful to know how much of a burden a construct imposes on the cellular capacity of the cell.

With teams being able to compare burden values this will benefit further research in multiple ways. Teams will be able to more thoroughly study evolutionary stability by knowing how long it takes their part to break. Also, by being able to standardly characterize parts as imposing a high burden or not teams will be more selective when choosing parts to work with. This standardized burden measurement will also possibly encourage teams to think about and test burden in organisms outside of e. Coli and further research how to alleviate burden from the host cell of a genetic construct.