Self-assembling DNA programmed by applying theoretical computer science to molecular engineering

Through the incorporation of computer science into molecular engineering, computer scientists from UC Davis and the California Institute of Technology developed DNA that can algorithmically self-assemble. Using a DNA set tile containing 355 single-stranded tiles, the scientists were able to construct 21 circuits that can execute algorithms ranging from obtaining an unbiased choice from a random biased source to stimulating cellular automata, according to a Nature article titled “Diverse and robust molecular algorithms using reprogrammable DNA self-assembly.”

“I hope that molecular engineers will understand that the best way to understand how to get their molecules to automatically do what they want is to program them, which is where computer science comes in,” said David Doty, an assistant professor of computer science at UC Davis. “At its core computer science is not about electronic computers. It’s about automation […] how to design automatic processes that just work — we call them algorithms — without any need for people to come in and direct things by hand.”

The initial idea for this research came from Erik Winfree, a professor of computer science, computation and neural systems and bioengineering at the California Institute of Technology, who published a paper titled “The program-size complexity of self-assembled squares” that incorporated ideas on how to make these molecules perform computation from his Ph.D. thesis.

“I have long been fascinated by the conceptual connections between the mathematics of geometrical tilings, the fundamental principles of theoretical computer science, the exquisite forms of crystals and minerals, the complexity of biological self-assembly processes and the elegant formalisms of statistical mechanics,” Winfree said. “All those threads come together here.”

Doty, who had originally been studying Algorithmic Information Theory at Iowa State University as a graduate student, was captivated by the notion that this theory could be implemented to create actual self-assembling DNA molecules which can form nanoscale structures. Doty began working on theoretical problems in the field before joining Winfree’s lab. Damien Woods, a professor at Hamilton Institute of Maynooth University, joined Winfree’s lab after Winfree’s arguments intrigued him. Although both researchers were unfamiliar with laboratory work, instead coming from a theoretical computer science background, the two worked together to implement the theory into actual experiments.

Woods identified a major step in their research to be functionalizing an error reduction technique called “2×2 proofreading,” which allows the creation of more complex systems. Once this technique could be implemented, they were able to design the DNA system to fully exploit proofreading.

“When we purchased our molecules and started our experiments, we knew of only three or four circuits (programs) that we could implement in the lab,” Woods said. “But because our DNA system was reprogrammable, we spent subsequent days, weeks and months figuring out a total of 21 circuits to implement experimentally. Programming at the lab bench. A wonderful experience.”

Doty explained that a large portion of the project was devoted to determining how to unzip the DNA in order to demonstrate that their experiment had worked. After working roughly six months to develop a method to unzip the DNA, the problem resurrected and forced the researchers to come up with new ideas.  

“You take years to do an experiment, and you think the first few months will be spent knocking out the boring mundane stuff just to get the system up and running, and the next several years doing cool things with it,” Doty said. “In reality it’s the reverse: the majority of the time on the project is boring mundane stuff, mostly focused on figuring out what doesn’t work by trying things over and over again and recording that they don’t work.”

Woods stated he was pleased with the range of algorithms implemented through the experiments and the mathematically proven theoretical results from their self-assembling DNA. According to Doty, although they concentrated on DNA because there are already synthesizing methods in place and the molecule is fairly predictable, the double helix structure and the negatively charged characteristic of the molecule made some of the procedures difficult. Doty stated that their research could serve as a stepping stone to learning the general principles of automated molecule engineering. The researchers have the opportunity to move from title growth causing the execution of an algorithm, as in their recently published paper, to exploring how algorithms can direct this growth, essentially turning around the arrow of causation. This could lead to 3D printing without a printer and growing an object controlled by algorithms.

“We are still in the early stages of exploring this jungle of ideas,” Winfree said. “Now that we’ve cut a trail to one lovely waterfall, so everyone can go there, I imagine that we’ll rest for a few days at our base camp to renew our energies and then pick up our machetes again and start hacking away at the underbrush to explore in a new direction, and see what we’ll find.”

Written by: Michelle Wong –– science@theaggie.org

Engineers without Borders at UC Davis provides sustainable solutions to empower underserved communities globally

Engineers without Borders applies engineering skills to provide solutions that elevate the quality of life in underprivileged communities in developing countries. The Davis chapter of the organization currently has three projects in Peru, Bolivia and Kenya and has had successful projects in both Peru and Nicaragua.

“EWB is a unique organization in that it has an impact on both the communities we partner with and on our UC Davis students,” said Professor Colleen Bronner, the faculty advisor for EWB at UC Davis.  “We help communities raise the funding […] for water and sanitation projects and provide some of the technical expertise needed for the designs.”

As members of EWB, UC Davis students learn resourceful construction techniques and create relationships with different cultures where both parties learn from each other. The hope is that, through the experience, students learn that underprivileged communities aren’t victims and instead have much to offer. They just don’t have the resources to do so.

“Many developing communities around the world have been positively impacted by the projects that EWB has completed,” said Tanisha Potnis, a fourth-year mechanical engineering major and president of EWB at UC Davis. “Projects are targeted at helping communities achieve basic human needs such as sanitation, water distribution and construction.”

The Peru project focuses on improving the water distribution system of La Huaylla in northern Peru. The current water distribution system doesn’t provide sufficient clean drinking water for the community it’s serving. Last year, the team traveled to Peru to build a reservoir to increase the amount of water that could be stored. This year, the team is returning to install new pipes in the current distribution system to minimize leaks and ensure they’re properly sized to maximize the amount of water stored. They’re hoping that providing a sustainable solution to La Huaylla will help spread awareness to neighboring communities.

“The community is made up of 250 households,” said Valerie Yanez, a fourth-year civil engineering major at UC Davis and the co-lead for this project. “The goal is that the community of La Huaylla will have access to sufficient quantity and quality of water […] especially during peak hours to meet demands.”

The Bolivia Project hopes to improve sanitation in the community of Parque-Colani by building sustainable latrines in every household. They will travel to Bolivia in the summer to present their designs, teach the community how to build the latrines and start the building process within the community.

“On a greater scale, we hope to educate the entire community of Parque Colani on some basic sanitation techniques that could help eliminate illness and [the] spread of disease in the community,” said Lauren Chew, a third-year civil engineering major and co-lead for this project. “In addition, we hope to be able to provide resources, such as reusable pads, and information on women’s health.”

The Kenya project is working with Mabinju, a village in southwest Kenya, where limited access to clean drinking water leads to the prevalence of waterborne illnesses. While this project is still in the early stages, the team hopes to travel to Kenya this summer to identify the community’s needs.

“With access to clean water, children will not be forced to miss school to fetch water, families will experience greater yield and income from agriculture and livestock and community members will not be exposed to harmful bacteria in water,” said Mark Susanto, a fourth-year mechanical engineering major and co-lead for this project. “In addition, our project will visit local schools to promote both STEM education and gender equality in all industries.”

EWB hopes to continue serving underprivileged communities and increase its presence on campus, diversifying the team to include members of all majors.

Written by: Kriti Varghese — science@theaggie.org

New research from UC Davis and other universities explores the curious characteristics of networks.

Networks like the internet, powergrid and brain control our lives, yet the underlying dynamics that define them are somewhat mysterious. One of the most fascinating dynamics is the natural tendency for behavior in networks to synchronize.

A famous example of network synchronization occurs in groups of fireflies. Certain species will start blinking randomly and then adjust until thousands of them turn on and off at the same time. Besides synchronous behavior, scientists have also observed more complex repetitive patterns that can emerge between network nodes. They call these exotic states.

A more detailed study of these states might allow scientists to better create and decipher complex networks. Recently, researchers from UC Davis, Caltech and other universities made a significant contribution to this field. On Mar. 8th, they published a paper in Science describing what they learned from a new ideal system they created to study network dynamics.

The experimental system the researchers built is a ring of eight electrically connected nano-mechanical oscillators. Each oscillator can be thought of as a clock with only the minute hand. The figurative clocks can spin independently, but through some novel experimental design, electrical connections between them allow the oscillators to influence their neighbors in the ring. The system is essentially an ideal recreation of the firefly network. Each node, the firefly or oscillator, acts independently but can interact with the other nodes. When the connections in the system are switched on, the figurative clocks spin in an uncoordinated manner. Then, like the fireflies, they slowly lock into a stable state.

One of the states the research team found was perfect synchrony; all the figurative clocks turned identically. However, they saw other exotic states with more curious behavior. For example, they observed splay states where the figurative clocks moved at the same rate and direction, but each each clock was slightly offset from its nearest neighbors.

Each emergent state was based on the starting conditions of the oscillators. The experimenters turned on the system with hundreds of different initial conditions and observed as the exotic states emerged. Many of these states had been predicted theoretically but never recreated in an ideal experimental setting, others were observed for the first time.

According to Matt Matheny, a research scientist at Caltech who was the principal author on the study, the team combined the experimental data and mathematical theory to better characterize exotic states and begin to explain how and why they emerge.

“What we did is that we went through, and we explained why you get this sort of different behavior and showed mathematically that if you write out the equations you can pinpoint how these strange behaviors are stabilized.”

According to Michael Roukes, one of the leaders of the research and the Frank J. Roshek professor of physics, applied physics and bioengineering at Caltech, such precise analysis was possible in this experimental system because the researchers had full control over almost every aspect.

“This is a really well behaved system where we can both measure everything that’s going on and control everything in the system,” Roukes said. “Those are the ingredients that now give us this very robust and detailed experimental platform to sort through the various theories that have been proposed, put them to the test and expand them where they don’t explain what is manifested in the real world.”

Although the systems we deal with on a daily basis have more than 8 nodes and are connected in dramatically more complicated ways, the simplicity of the experimental system allowed the scientists to get a better understanding of the fundamentals of networks in a way that an observational study of complicated networks would never allow.

According to Raissa D’Souza, a professor of computer science and mechanical and aerospace engineering at UC Davis and another author on the paper, the team was pleasantly surprised by the sheer variety of exotic states that could emerge from a simple 8 node system. They were also daunted by what that could mean for more complicated real world networks.

“It’s the simplest kind of structure that we could think of, and already in that simple structure we see beautiful unanticipated patterns of coordinated behavior,” D’Souza said. “It’s a little staggering and exciting to think about what would happen if we start scaling up the complexity of the network beyond that ring.”

Yet scaling up the complexity of the network is exactly what the team plans to do next. They want to answer more questions about the fundamentals of synchrony and exotic states in more complicated systems.They’d like to see if it is possible to push the system between exotic states.

“One of the things that we really want to do is understand how we can nudge the system to go from one type of exotic state to a different type of exotic state,” D’Souza said. “We’d like to give it a small little push and take advantage of the natural dynamics of the system to push it from one behavior very simply to a different kind of behavior.”

This ability to nudge systems between states could potentially allow scientists to better control large scale networks and help manage issues in the human brain.

The researchers believe that one day, an understanding of exotic states may help make all sort of systems better.

Written by: Peter Smith – science@theaggie.org