Dr. Oliver Medvedik is the head instructor of Cooper Union’s 2014 iGEM team. He is also a co-founder of Genspace, a community lab in Brooklyn. This year, Cooper Union’s iGEM team worked on a project called μToolBox, dedicated to creating tools for synthetic biologists. The project as a whole aims to address issues faced by synthetic biologists, including faster DNA synthesis, biosafety, and education. The project consists of three components: the De novo Enzyme Mediated Oligonucleotide Synthesizer, the Programmable Lifespan Timer, and the Biohacker Kit. The inspiration behind these projects comes from Dr. Medvedik’s experience as a researcher and educator in the synthetic biology field, as well as his involvement in Genspace.
The first component, the Synthesizer, is intended to tackle one of the most pressing issues in synthetic biology today: DNA synthesis. According to Dr. Medvedik, the project aims at compressing the so-called design-build-test-learn cycle, in which scientists design an experiment, build it from DNA, and test the results. The most time-consuming part of this cycle is the building phase, where scientists are required to order the DNA and put it together. Currently, scientists who work with DNA have to buy it in small parts commercially, because it is not economically feasible to make in the lab. The team worked to compress the “build” part of the cycle by finding a way to synthetize DNA cheaply and quickly in the lab. They did this using an enzyme, terminal transferase. Its normal function in cells is to add random stretches of the building blocks of DNA (Adenine, Cytosine, Guanine, and Thymine) to the ends of cut DNA. The team instead used modified versions of these building blocks, containing “reversible protective groups”, in order to “tame” the enzyme into building DNA in a more controllable manner. “Ideally we want to create a microfluidic device that does all of the (building) work for you in a programmable way“, says Dr. Medvedik. Currently, the team is working by hand to make a small piece of DNA called a promoter, and will be testing the promoter once it is synthesized to see whether it functions biologically. If it does, the team will move on to automating the system on a micro-scale. As a first step, Karlin Yeh, a gifted Cooper Union student, designed and built a robotic macro-fluidic device for expediting the repetitious steps required to assemble a strand of DNA. According to Dr. Medvedik, this system can be considered a gateway technology, one that would allow other technologies to accelerate and grow:
“if the technology works the way it is supposed to work, it will make all other forms of genetic engineering in a test tube obsolete”.
The second subproject, the Programmable Lifespan Timer, addresses the issue of biosafety in synthetic biology. The team created a strain of yeast that will not be able to thrive outside of the lab in case it accidentally got out. Yeast is commonly used in industry, especially in pharmaceuticals, because it can be engineered to secrete many useful compounds. Accidental leakage can be problematic because the cells may secrete these compounds outside of the lab where the compounds endanger natural ecosystems. This problem may be exacerbated because communities of yeast cells are immortal and can grow rapidly, as cells replicate and regenerate. To address this issue, the team engineered a strain of yeast that has a programmed lifespan and is unable to replicate, so that if the yeast got out of the laboratory it will not grow but rather age and die. In order to do this, the team created yeast cells that lack an enzyme used in the regeneration process. As explained by Dr. Medvedik, every time the DNA in a yeast cell replicates, the chromosomes shrink a little. Usually, an enzyme called telomerase fixes the ends of the chromosomes to prevent aging. Without this enzyme, and by removing other key components, the chromosomes will continue to shrink, causing the cell to age and die. The team created yeast cells that do not have this enzyme. These cells are capable of growing long enough to produce the compounds they were engineered to produce, but if the population is not replenished, the cells will simply die and the population will crash. “This way there is a safety system built into the organism itself, so that in case the lab’s hard safety protocols fail, the system itself would be intrinsically incapable of getting out of control”.
The third component of Cooper Union’s iGEM project, the Biohacker Kit, originated from the need to have an easy and fun way to teach synthetic biology. This part of the project aims to accelerate the “learn” part of the design-build-test-learn cycle. According to Dr. Medvedik, although building a biological system is an important part of synthetic biology, is it not the fun part, and some people would prefer to simply design a system and test it, skipping over the building phase. “The analogy here is that some people just want to drive a car, not everybody wants to build the engine before they drive. If you required everyone to assemble their own car, there would be a lot less people on the road today”. The kit allows students to come up with experiments, design them, and test them without having to put together the DNA. It is comprised of two circular pieces of DNA called plasmids. One piece determines what stimulus activates the system, and the other determines what reaction the system will have to the stimulus. For example, if you want to create a cell that can detect toxins by turning blue, you could take a plasmid that codes for sensitivity to the toxin, and put it in the cell along with the plasmid that codes for turning blue. This would result in a cell that turns blue in the presence of toxins. The Cooper Union team is now in the process of creating different plasmids that code for different properties, so that users have more options of how to engineer their systems.
“I think we need more experiences like iGEM and more organizations like Genspace. Genspace as an organization can’t accommodate every person who wants to do a biotechnology project, and the iGEM competition can’t accommodate every student who wants to compete in a synthetic biology competition. I think the spectacular success of both organizations shows the need for more such opportunities around the world.”
The ideas behind many of these projects, especially the Biohacker Kit, originate from Dr. Medvedik’s work in Genspace, a community laboratory in Brooklyn. Genspace is open to the public and is dedicated to promoting citizen science and access to biotechnology. Dr. Medvedik is one of the co-founders of the lab: “I wanted to set up a biotechnology laboratory that would enable me to work with people in groups that are not normally associated with the field of biotechnology, such as designers and architects”. Along with the other co-founders, he created a space where anyone, regardless of background and education, could learn about biotechnology and design a project. “I think we’re going to see a lot of cool projects pop up from these non-traditional spaces, and as synthetic biology expands and develops outwards we’ll see more applications of it in fields that we don’t normally associate with biotechnology.” Genspace creates opportunities for less experienced researchers to develop more laboratory skills. They offer workshops and courses to get members familiar with the field and with working in a lab environment. New members can also get apprenticed by helping more experienced members with their projects, or by reaching out and asking for assistance from the Genspace team. Genspace also dedicates time to mentor undergraduate students, and participated in iGEM this year in the Community Labs track, under the guidance of co-founder Dr. Ellen Jorgensen.
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