Cornell undergrads harness bacteria to clean up toxic site

Students developed a water filtration system using genetically engineered bacteria to sequester heavy metals; now they’re taking it to the iGEM competition

View of the gorges, Cornell University, Ithaca, New York (Photo by Eric Holmes)

Every fall, hundreds of people choose to seize the day and hurtle themselves off a 50-foot cliff. Crashing down into the waves, they plunge into cool water only to reemerge to blinding sunlight in their eyes and the wild hollers and cheers of their friends from up above.

View of Beebe Lake, Cornell University, Ithaca, New York (Photo by Eric Holmes)Exploring the gorges and, more often than not, taking a dip on the way down are common pastimes, even regarded as a tradition in the small town of Ithaca, New York, population 30,000. Ithaca is home to Cornell University. Students and locals alike are constantly awed by the wondrous natural scenery that has earned Ithaca the title of "10 square miles surrounded by reality." Nowhere else in the country would you be able to pass a gaping gorge dropping off a hundred feet into a jagged ravine and get splashed by a thundering waterfall on the way to class.

In the fall, the foliage lights up the small town of Ithaca with warm burnt sienna, bright yellow and bold scarlet hues amidst the rolling hills. Ithaca is gorges. A strong sense of environmentalism runs deep in the community and university.

But just outside of campus in the Fall Creek neighborhood, the site of the former Ithaca Gun Factory tells a different story.

Established in 1880, the Ithaca Gun Factory manufactured an assortment of guns and rifles for World War II and the Korean War until it shut down in the 1980s. In later years, the factory was accused of contaminating the land with lead, and after an unsuccessful Superfund remediation effort, the surrounding land and water supplies remain highly suspect.

The environmental dilemma remains unbeknownst to many students, especially those currently living in the Gun Hill apartment complex that has since been constructed nearby. Grace Livermore, a second-year at Cornell, visited the site over the summer to see for herself:

I wanted to see what kind of aftermath the Ithaca Gun Factory left after it deserted Ithaca. ... I found some discarded shells on the ground, lots of standing water, the remnants of the factory building and the gun factory's tower. The land seemed blocked off, as if they were just trying to forget about it.

The sign found outside Ithaca Gun Factory indicates lead contamination (Photo by Grace Livermore)The smokestack is the only remnant of the Ithaca Gun Factory after the factory was demolished (Photo by Grace Livermore)

But this time, forgetting about it was out of the question. Livermore was a member of Cornell's International Genetically Engineered Machines (iGEM) research team, and word quickly spread faster than lead leaching through soil. Fortunately, while the latter is diffusion-limited, the rate of gossip among college students knows no bounds. In no time, the subject came up at the weekly team meeting.

There was no doubt that this was a pressing issue, but what could a group of 30-odd undergraduate researchers in synthetic biology do to help? The answer was so obvious yet so impossibly and fantastically whimsical, as if proposed by a 5-year-old who had only recently been lit up by the spark of science. There are 5 million trillion trillion bacteria (5 with 30 zeros) on Earth, and they are everywhere. Why not reengineer a bacterium to sequester the lead to clean the water? Consider it a testament to the remarkable feat of scientific pursuit that such a task is now possible.

Entering their technology in the a global competition

As it turns out, that is exactly what the Cornell iGEM team set out to do. If successful, we have a good chance of winning a gold medal at the competition.

The iGEM (International Genetically Engineered Machines) competition is a global synthetic biology contest that encourages undergraduate students, graduate researchers and entrepreneurs to develop novel uses for synthetic biology targeting current problems in the environment, industry and medicine. At its core, the iGEM competition is a venture to spur scientific innovation, spread awareness and encourage acceptance for the revolutionary albeit controversial new field of synthetic biology. From October 30 to November 3, Cornell iGEM will join 200 teams from around the world at the iGEM 2014 Giant Jamboree in Boston present their project: a variant of Escherichia coli (E. coli) bacteria that can be used to filter heavy metals such as lead, mercury and nickel from contaminated waters.

The Cornell iGEM research project is just one of the many possibilities made feasible by advancements in synthetic biology. Synthetic biology is an inherently interdisciplinary field that seeks to expand the limits of biotechnology and build optimized biological systems to do everything from processing information to producing energy to improving human health.

The genetic revolution was set into motion in 1953 with James Watson and Francis Crick's monumental discovery of the molecular structure of DNA. Since then, the public and indeed the world has been gripped with the overwhelming possibilities and implications involved with deconstructing nature's genetic code. The renowned evolutionary biologist and popular author Richard Dawkins once stated, "DNA neither cares nor knows. DNA just is. And we dance to its music."

Sharlene Dong designed this infographic with imagery from iGEMBut times have changed. It takes two to tango, and scientists are quickly finding out that they can alter the beat to make DNA dance just as they please. It is precisely this fact that makes synthetic biology unique. By pasting together snippets of genetic code from a wide range of species or synthetic constructs, scientists can potentially direct cells into exploiting existing pathways and producing wholly unprecedented configurations.

How the science works

This engineering mindset of bottom-up construction was the foundation of Cornell iGEM's plan to genetically engineer E. coli to sequester lead, nickel and mercury and integrate it within a high-throughput filtration system, essentially utilizing bacteria to remove contaminants from water in local lakes and rivers. Normally, bacteria possess multiple barriers from the environment, including an outer cell wall made up of a tight cross-linked layer of polymers called peptidoglycan and an inner plasma membrane composed of two phospholipid bilayers. This combination makes exchange with the environment extremely selective; normally such toxic inorganic metals would have no chance of entering the cell. To maneuver around this problem, researchers transformed bacteria to produce heavy metal transporter proteins that will lodge themselves into the membrane, catching the metals passing outside and bringing them into the cell interior. From there, a second type of protein called a metallothionein will bind tightly to the metals. So far the team has collected encouraging data to support their proposed biological system and hope to transition from the lab to the field after the competition.

Building on past projects

This is not the first time Cornell has targeted an environmental problem for their research project. In fact, this year's project was developed as an offshoot of work the team had done two years ago. The project was called SAFE BET, short for "Shewanella Assay for Extended Biomonitoring of Environmental Toxins," and aimed to genetically engineer the Shewanella oneidensis bacteria to upregulate metal reduction pathways to generate a current in response to presence of arsenic and naphthalene in water. Engineers on the team also took advantage of the opportunity to build a field deployable bioreactor system to allow for remote monitoring, solar-powered panels and wireless transmittance of data to a mobile application. In 2013 the group developed a fungal toolkit to optimize the construction of a biodegradable fungi-based Styrofoam substitute.

Their efforts have not gone unnoticed. The Cornell team won the International Human Practices award in 2013 and the North American Regional Human Practices award in 2012 and 2013 for their efforts in spreading synthetic biology awareness and encouraging critical thought and ethical discussion. The 2012 SAFE BET project also won the "Best Solution to an Oil Sands Problem" from the Oil Sands Leadership Initiative.

Elsevier Connect Contributor

Sharlene DongSharlene Dong is a fourth-year undergraduate at Cornell University in Ithaca, New York, studying chemical engineering and biochemistry. She is deeply interested in biotechnology, medicine and current trends in higher education but also dabbles in cooking (and sharing) fun foods, distance running and photography.

Dong has also been an active part of the Cornell Genetically Engineered Machines research team, which focuses on synthetic biology and genetic engineering. She loves "talking about interesting things and big ideas," and you can find her on Quora.

Here, she writes about a project the team is entering into the iGEM (International Genetically Engineered Machines) competition in Boston.

Deciding on a single project proposal was no easy feat. Training a group of 20 new researchers proved to be even more challenging. Even before the team returned to university from winter break, team members were exchanging project ideas and reviewing 70 new applications searching for their newest comrades. Together they would solemnly swear that they were up to no good and embrace Cornell Engineering's new motto to "break the rules" in their never-ending scientific pursuit. Second year student Michelle Zhang expresses the sentiment perfectly. "I enjoyed my experience in lab mostly because of the people I'm with. We joke around all the time. ... We're all so different but we all connect and are pushing each other towards the same goal. It's really motivating."

The iGEM members all have different reasons for joining the team. Alex Han is a recent Cornell iGEM alumnus and now a graduate student at Stanford University. He attributes his initial interest to his study abroad experience in Copenhagen, where he learned about metabolic engineering and says that "it really opened up my eyes to synthetic biology as a whole." For Zhang, joining iGEM was a way to "find a place where I can do what I like and also branch out to people beyond my core group at Cornell. ... I wasn't sure exactly what I was getting myself into."

As with any scientific endeavor, uncertainty lies in every corner. One of the most remarkable things about Cornell iGEM is that it is completely student-run. Although there is an official advisor who handles some administrative tasks (Dr. Xiling Shen, Assistant Professor in the Department of Electrical and Computer Engineering), the entire brainstorming process and lab work are done by the students. It is essentially a research lab directed by undergraduates, with the senior half of the team teaching the novices; when you stop and think about it, that is a terrifying thought. Yet chaos and cooperation meld together in perfect synergy and makes the final accomplishment even more unbelievable. This brings a smile to team lead Eric Holmes, a third-year biological engineer with a shock of shaggy blonde hair and an easy-going smile. He remarks, "One of the most difficult things for me this season has just been to take a step back and let the team do their work. We have so many people and so much collective talent. There is just a lot of potential here and I want to let that shine."

The summer is when the Cornell iGEM team does a majority of the work, including arranging subteams, ordering lab materials and doing preliminary wet lab trials with genetic constructs. They also contact corporations in the region, some of which have donated equipment and materials.

But summer is ephemeral, coming and going with the breeze and fading with the rays of sunlight shining on Libe Slope. With the advent of fall comes an impending competition, increasing amounts of coursework and other extracurricular commitments. If September is bad, October is worse.

It's almost midnight — back to the lab

On one particularly dreary night, some team members stop by the local bubble tea shop. They are frequent visitors, but this time they are at the corner table, slumped against the wall and pensively staring at the shiny black boba pearls at the bottom of the cup. You can see the strain in their eyes after a long week of challenges in the lab. Machines malfunctioning. Cells returning negative yields from experiments. Running out of stocks of buffer and primer solutions. Everyone seemed to agree though that the final flourish was the realization that the genes on the plasmids of the bacterial stocks had inadvertently been frozen for the past 10 years. Obstacles like that were far too common, and time was running out.

Mendeley and iGem

Alice Atkinson-BonasioMendeley, the research collaboration platform and company that joined Elsevier in 2013, has been supporting innovative iGem research. The first team to approach us was made up of eight Yale undergraduates, who aimed to engineer a common bacteria to produce polylactic acid (PLA), a biopolymer that is cheaper, cleaner to make, and biodegradable. They won a silver medal at the iGEM North American Regional Jamboree and advanced to the World Competition in Boston.

Mendeley has provided the Yale and Cornell teams with a free upgraded team package, which gives more scope and flexibility for collaboration within a group. This collaborative workspace helped iGem teammates to connect and move the project forward even as some of them were dispersed around the world pursuing summer opportunities, explained Edward Kong of the Yale team:

Our university software library offers a few options for reference managers, but Mendeley is more useful to us because it enables a collaborative workspace that doesn't require us all to be in the same room. In our team, we might have three full-time student researchers in our summer lab while the rest of our researchers may be pursuing other opportunities around the world, so we can't always meet face-to-face.

Read his full post on the Mendeley Blog.

— Alice Atkinson-Bonasio, Communications Manager for Mendeley

The Yale iGem Team

The fluorescent lights in the tea shop glowed and illuminated the raucous hordes of college students mingling outside on the street, searching for one more party. "Okay, I got to go," third-year student Olya Spassibojko says and stands up. "Gotta go run one last gel. Fingers crossed that it works." It's almost midnight on a Saturday night, but the competition waits for no one.

It's raining again in Ithaca, and the rains sloshes over the streets. It's a long way from Collegetown to the biotechnology building, Weill Hall, but soon the fluorescent lights from the local convenience store and the loud crowds and blasting music from the local bar fade away, enveloped behind by a thicket of forests. The towering white biotechnology building, Weill Hall, with its stark avant-garde architecture, stands at the top of the hill and surveys the campus.

It's eerily quiet in Weill. The basement is a dark winding labyrinth, and you can hear the footsteps echoing and the doors clicking shut automatically behind you. A familiar whirring sound of the PCR machine and incubator fills the room upon entering the lab space. There is a stack of bright orange pipette tip boxes in the corner and at least a hundred Petri dishes filed neatly in columns, empty and filled with a viscous agar layer, labeled and circled and with doodles scrawled on them. A "Cornell iGEM" logo drawn and decorated in dry erase marker is still on the board from the previous year, right beside the shelf of trophies. Somehow, the lab space does feel a bit like home.

For now, the clock is ticking and the countdown to November continues. The final competition is considered the culmination of a year's worth of work, and teams will be judged on the novelty and success of their project as well as collaboration with other teams, human practices advances and number of successful genetic constructs synthesized and submitted. For many, the experience has exposed them to new scientific ideas and cultures and allowed them to expand their network on a global scale. Competition is second-year Jonlin Chen's favorite part of the entire experience. "Oftentimes when you are working hard in the wet lab over the summer, you forget that you are, in reality, a part of a huge network of iGEM teams, all of whom share the same passion for synthetic biology. ... It makes you realize that iGEM is truly an international phenomenon that stretches far beyond campus."

Where do we go from here?

The big question at the end of the road, once November comes and goes, is "where do we go from here?" What does iGEM want students to take away from their experience? Where is synthetic biology going, as a whole?

For some students, iGEM truly has been a life-altering experience. Ryan Muller is only a fourth-year undergraduate at Arizona State University, but after leading the ASU iGEM team, he capitalized on the research experience gained in order to cofound a biotechnology startup company, HydroGene Biotechnologies, which develops a portable pathogen biosensor capable of detecting waterborne and foodborne pathogens. Numerous other startups, such as Ginkgo Bioworks, Darwin Toolbox and Genomikon, have also blossomed from iGEM ventures.

In the academic setting, synthetic biology continues to make strides and push its way into mainstream research as an upcoming revolutionary new field. One particularly promising example is artemisinin, an antimalarial drug developed from research by Dr. Jay Keasling from the University of California, Berkeley.

Scientific progress is unrelenting and the future teeming with possibilities. What lies in store after iGEM could be anyone's guess.

Ultimately, the iGEM competition is an educational tool, designed to inspire the next generation of scientists to experiment, wonder, create and chase after something with passion and unyielding drive. After witnessing iGEM's exponential growth across all demographics, from high school students to entrepreneurs, it seems like iGEM does exactly what it set out to do: hijacking students' love of science and driving them to innovate and produce something unlike anything seen before.

Whether Cornell iGEM's vision of using synthetic biology to improve water quality is successful or not, the world will have to wait to find out, but ultimately the scope of iGEM extends far beyond any individual project. For Cornell, these possibilities may be the key to sustaining the beautiful landscapes that are so integral to its identity, allowing future generations the same opportunity to marvel at the same pristine gorges and far more importantly, continue being reckless college kids and jumping off gorges for sport.

iGEM expands to high school level

Susan Liu is the founder of the iGEM team at Montgomery High School in Skillman, New Jersey.The International Genetically Engineered Machines (iGEM) Foundation started in 2003 originally as a month-long course at MIT. Since then, the competition has expanded its reach and grown exponentially. In 2014, there were 245 teams registered in the collegiate division (82 from Asia, 67 from Europe, 14 from Latin America and 84 from North America). One of the goals of iGEM is to expand accessibility to synthetic biology so it is apt that the iGEM high-school division is also growing (54 teams in 2014) and drawing attention.

Montgomery High School senior Susan Liu, the founder and current project team lead for Montgomery iGEM (Skillman, New Jersey), said she was first introduced to iGEM by an alumnus from her school. "Since our school didn't have many outlets for lab-based or medicine-focused clubs, a few of my friends and I immediately latched onto this idea," she said. "We were hesitant to believe that high school students could engage in synthetic biology and biological engineering."

She has had help from fellow Montgomery High School senior Robert Dembinski, and together they work to bring opportunities for research, presentation and management. Since its initial inception, Montgomery iGEM has grown to a team of 55, divided into 2 subteams: Research and Development and Operations Management. Liu encourages this growth since "in high school, we need all the help we can get and one of our main goals is to inspire the next generation."

As with many teams, fundraising is a tough sell, but Montgomery iGEM managed to pull through with private contributions from team members, bagging fundraisers and borrowing lab equipment from the school. For Liu, her favorite memory was discovering a key mechanism that validated their entire project.

Liu said the overall iGEM experience has been a tough albeit rewarding route for her and her team: "This process of research, development and symposium presentation gave us our first view of the professional scientific world. Personally I'm planning on majoring in biomedical engineering or biotechnology, and I'm sure there are many other members of the team who are guided the same way."

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