Building Better Bacteria

 

The 2015 iGEM teams from the University of Texas
The 2015 iGEM teams from The University of Texas at Austin

For the past few months, a team of students from the Hijacking Microbial Factories for Synthetic Biology stream has worked to keep bacteria from doing what they do best: evolving.

One of the biggest problems that synthetic biologists face today is ensuring that the changes they make to bacteria continue working for as many generations as needed. A group of student researchers from the stream manipulated the bacterium E.coli  to look for the mutations that ‘break’ artificial modifications, and in turn keep cells from producing the proteins that they were programmed to make.

The researchers presented their work in Boston for the International Genetically Engineered Machine, or iGEM, competition this September. The event, called the Giant Jamboree, included the work of 280 teams from universities worldwide.

Minimizing the mutations that cause cells to change over time would be a huge benefit to synthetic biology research. Dennis Mishler, the Research Educator for the Synthetic Biology Stream, explained that “evolution is great for things that want to live and grow and survive,” but is “really bad for people who want to reprogram bacteria.” When mutations cause cells to stop doing what researchers program them to do, they tend to be able to save more energy, making them better at surviving than their modified counterparts. Even small changes to their genetic programming can change entire populations over short spans of time.

The basic procedure the team used was to create plasmids, loops of DNA that contain the sequence of DNA that scientists choose to modify, or the genetic device. These plasmids are then introduced to cells within a culture. Students programmed these cells to produce fluorescent proteins, which can be measured by the intensity of light they give off.

Once a significant amount of the florescence had decreased, researchers knew that the genetic device was no longer working correctly, and that most likely many of the cells had stopped producing these proteins. They then chose a representative colony of the bacteria to send out for DNA sequencing, which allowed them to check for mutations.

After testing, Computer Science Major Tyler Rocha says that the team found two groups of devices, those that were “either very unstable or very stable.”

This research has helped improve the Evolutionary Failure Mode Calculator, an online form developed by the Barrick lab in the Department of Chemistry that allows users to insert the genetic sequences of their cultures and detect mutational hotspots. “Our hope is to make this calculator available to a lot of synthetic researchers,” said Sanjana Reddy, a Biology Major on the team.

Continuing with research from previous years, the 2015 iGEM team also worked to build genetic devices with real world applications. In 2012 students from the stream’s iGEM team pioneered a plasmid that would allow bacteria to break down methylxanthine compounds, with the intention of determining how much caffeine different beverages contain. This plasmid works well for artificial drinks like sodas, which contain pure caffeine solutions, but organic beverages like tea and coffee contain other methylxanthine compounds that are highly similar to caffeine, making it hard to measure exact amounts of caffeine. This year’s team, led by senior Alex Gutierrez, created a set of plasmids which together can determine the concentrations of each compound, including caffeine.

Plate from SXSW outreach program.
Plate from SXSW outreach program. Courtesy of the Barrick lab.

To meet iGEM community outreach recommendations, researchers set up a booth at the South by Southwest festival, encouraging people to ‘paint’ with modified bacteria and sending back pictures of their glowing plates afterwards. “Synthetic biology is something that not everyone is on board with,” Neuroscience Major Natalie Schulte said, “a lot of that comes from people not understanding what it is.”

The team presented their findings this September alongside groups from other US and international institutions. They team completed a 20 minute presentation and a ten minute Q & A session. Schulte accredited the large audience to the fundamental nature of the project, explaining that “all of those projects are in a way dependent on evolutionary stability.” The aptly named ‘Breaking is Bad’ project received an individual gold standard, awarded to fewer than half of the competing teams.

Looking forward to next year, the students are excited about starting on ideas from the spring semester which warrant more attention, or continuing with current projects, such as evolutionary stability, which still have potential for improvement. Dr. Mishler described plans for projects turning bacteria into living sensors for pH and temperature, and making bees more resilient to external chemicals like pesticides.

Kate Thackrey

UT Journalism Student

Faces of FRI: Pato Lankenau

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Pato Lankenau, a third-year Computer Science Major, will be graduating this spring.

When he started out in the Autonomous Intelligent Robotics stream, Patricio (Pato) Lankenau had no idea that he’d soon become known as the ‘quadcopter guy’ for his research teaching paradrones to scan their environments. For his independent research, Lankenau used a Microsoft Kinect® to track the trajectory of a Ping-Pong ball and command a quadcopter to move in 3-d space to catch it.

Now whenever the lab needs to show off its aerial skills Lankenau is the one behind the controls. Robotics research is a new experience for the Computer Science major, who mentioned that “it’s fine when it’s a computer that will crash, but it’s not fine when it’s a quadcopter that’s coming at you.”

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Student Researchers work in the Autonomous Intelligent Robotics Stream lab.

The project is an extension of the Turing Scholars student’s fascination with localization. Lankneau is currently working on his honors thesis with the Principal Investigator of the robotics stream, Peter Stone, to track objects as they move through non-static environments. Today interactive robots create permanent maps of the objects around them, so there’s currently “no way to differentiate between a wall that’s unlikely to move and a table or chair or even a person,” according to Lankenau. A better system would incorporate multiple robots to form a more accurate representation of the environment, an idea which Lankenau hopes to explore using the Building-Wide Intelligence Project of five robots located in the Gates-Dell Science Complex.

Matteo Leonetti, the Research Educator for the Robotics stream, says that Lankenau stood out in lab from the beginning, adding that he is “passionate about computer science and research, ambitious and competent,” and that “working with him has been a pleasure.”

Lankenau’s successes aren’t confined to university programs: after showing a friend a project he was working on freshman year, Lankenau was brought in on the ground floor of a technology startup, NetworkLift. The web service used algorithms to trawl Instagram profiles and customize a user’s account actions in order to grow a following. The team found that the most effective way to gain new followers is through systematically liking photos, successfully managing the accounts of celebrities and public figures. Lankenau left the company when it moved from Texas, but noted that it has since expanded to include other social media platforms.

Along with artificial intelligence, Lankenau developed an affinity for distributed systems while completing an internship at Apple, where he worked on iCloud storage systems. Distributed systems are fault tolerant, meaning that if one part of a system fails, the information contained within isn’t compromised. Talking about his work with information, Lankenau said “you want the data to be set up in a way that hard drives can fail, machines can die, and you never lose the integrity of the user data.”

Accomplishing so much in a just a few years requires making some sacrifices. Lankenau stopped watching TV in favor of working on coding and taking time to network, saying that “if you manage your time well you have plenty of time to do other interesting things.”

One of the extracurriculars Lankenau promotes is going to meetups in your field of interest. By introducing himself to specialized communities within Austin, Lankenau has made valuable connections outside of UT. Company recruiters aren’t looking for the work students do in class, “because everybody does that,” he said. Instead, students should do work outside of class and use their free time wisely in order to be competitive.

Lankenau is looking forward to a career in distributed systems after he graduates with the class of 2016, and has full-time offers from Apple and Uber. Lankenau is compelled to return to Apple in order to continue working with Bernard Gallet, a Sr. Engineering Manager of a team that specializes on Apple infrastructure projects, after completing an internship together over the summer. According to Lankenau, Gallet is a visionary with innovative views for where his team should be in the next few years. “I want him to be my mentor, so I definitely want to stick to him,” Lankenau said.

Kate Thackrey

UT Journalism Student

This article was the first in a continuing series of  monthly features on FRI students, called Faces of FRI. Expect to learn about a distinguished FRI student on the first FRIday of every month.