Programmed to Fold: RNA Origami

Researchers from Aarhus University in Denmark and Caltech have developed a new method for organizing molecules on the nanoscale. Inspired by techniques used for folding DNA origami—first invented by Paul Rothemund, a senior research associate in computation and neural systems in the Division of Engineering and Applied Science at Caltech—the team, which includes Rothemund, has fabricated complicated shapes from DNA's close chemical cousin, RNA.

Unlike DNA origami, whose components are chemically synthesized and then folded in an artificial heating and cooling process, RNA origami are synthesized enzymatically and fold up as they are being synthesized, which takes place under more natural conditions compatible with living cells. These features of RNA origami may allow designer RNA structures to be grown within living cells, where they might be used to organize cellular enzymes into biochemical factories.

"The parts for a DNA origami cannot easily be written into the genome of an organism. An RNA origami, on the other hand, can be represented as a DNA gene, which in cells is transcribed into RNA by a protein machine called RNA polymerase," explains Rothemund.

So far, the researchers have demonstrated their method by designing RNA molecules that fold into rectangles and then further assemble themselves into larger honeycomb patterns. This approach was taken to make the shapes recognizable using an atomic force microscope, but many other shapes should be realizable.

A paper describing the research appears in the August 15 issue of the journal Science.

"What is unique about the method is that the folding recipe is encoded into the molecule itself, through its sequence." explains first author Cody Geary, a postdoctoral scholar at Aarhus University.

In other words, the sequence of the RNAs defines both the final shape, and the order in which different parts of the shape fold. The particular RNA sequences that were folded in the experiment were designed using software called NUPACK, created in the laboratory of Caltech professor Niles Pierce. Both the Rothemund and Pierce labs are funded by a National Science Foundation Molecular Programming Project (MPP) Expeditions in Computing grant.

"Our latest research is an excellent example of how tools developed by one part of the MPP are being used by another," says Rothemund.

"RNA has a richer structural and functional repertoire than DNA, and so I am especially interested in how complex biological motifs with special 3-D geometries or protein-binding regions can be added to the basic architecture of RNA origami," says Geary, who completed his BS in chemistry at Caltech in 2003.

The project began with an extended visit by Geary and corresponding author Ebbe Andersen, also from Aarhus University, to Rothemund's Caltech lab.

"RNA origami is still in its infancy," says Rothemund. "Nevertheless, I believe that RNA origami, because of their potential to be manufactured by cells, and because of the extra functionality possible with RNA, will have at least as big an impact as DNA origami."

Rothemund (BS '94) reported the original method for DNA origami in 2006 in the journal Nature. Since then, the work has been cited over 2,000 times and DNA origami have been made in over 50 labs worldwide for potential applications such as drug delivery vehicles and molecular computing.

"The payoff is that unlike DNA origami, which are expensive and have to be made outside of cells, RNA origami should be able to be grown cheaply in large quantities, simply by growing bacteria with genes for them," he adds. "Genes and bacteria cost essentially nothing to share, and so RNA origami will be easily exchanged between scientists."

 

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Katie Neith
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Frank E. Marble

1918–2014
Frank E. Marble, the Richard L. and Dorothy M. Hayman Professor of Mechanical Engineering and Professor of Jet Propulsion, Emeritus, at Caltech, passed away on August 11. He was 96.
 
Marble received his bachelor of science degree in 1940 and his master's degree in 1942, both from the Case Institute of Technology. He then came to Caltech and earned an engineer's degree in 1947 and a PhD in 1948, with Professor Theodore von Kármán as his advisor. He was hired at Caltech in 1948 as an instructor in aeronautics, became assistant professor of jet propulsion and mechanical engineering in 1949, associate professor in 1953, professor in 1957, and was named Hayman Professor of Mechanical Engineering and Professor of Jet Propulsion in 1980. He retired in 1989. 
 
Marble made major contributions to aerodynamics, combustion, and propulsion, specifically the research and development of gas turbines and rockets. He also was responsible for the training of several generations of scientists in the field of aeronautics. 
 
A member of both the National Academy of Engineering and the National Academy of Sciences, Marble received many honors for his contributions, including the 1999 Daniel Guggenheim Medal, awarded by the American Institute of Aeronautics and Astronautics (AIAA), and the AIAA Combustion Award. 
 
Marble was predeceased by Ora Lee, his wife of seven decades. 
 
A full obituary will be posted at a later date.
 
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Study of Aerosols Stands to Improve Climate Models

Aerosols, tiny particles in the atmosphere, play a significant role in Earth's climate, scattering and absorbing incoming sunlight and affecting the formation and properties of clouds. Currently, the effect that these aerosols have on clouds represents the largest uncertainty among all influences on climate change.

But now researchers from Caltech and the Jet Propulsion Laboratory have provided a global observational study of the effect that changes in aerosol levels have on low-level marine clouds—the clouds that have the largest impact on the amount of incoming sunlight that Earth reflects back into space. The findings appear in the advance online version of the journal Nature Geoscience.

Changes in aerosol levels have two main effects—they alter the amount of clouds in the atmosphere and they change the internal properties of those clouds. Using measurements from several of NASA's Earth-monitoring satellites from August 2006 through April 2011, the researchers quantified for the first time these two effects from 7.3 million individual data points.

"If you combine these two effects, you get an aerosol influence almost twice that estimated in the latest report from the Intergovernmental Panel on Climate Change," says John Seinfeld, the Louis E. Nohl Professor and professor of chemical engineering at Caltech. "These results offer unique guidance on how warm cloud processes should be incorporated in climate models with changing aerosol levels."

The lead author of the paper, "Satellite-based estimate of global aerosol-cloud radiative forcing by marine warm clouds," is Yi-Chun Chen (Ph.D. '13), a NASA postdoctoral fellow at JPL. Additional coauthors are Matthew W. Christensen of JPL and Colorado State University and Graeme L. Stephens, director of the Center for Climate Sciences at JPL. The work was supported by funding from NASA and the Office of Naval Research.

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Kimm Fesenmaier
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Sink or Swim: Students Prep for RoboSub Competition

For the past year, a team of Caltech students has been meeting at the campus pool on Sunday afternoons to prepare for a competition—but they haven't been shooting for faster lap times or flip turns. Advised by professor Joel Burdick of the Division of Engineering and Applied Science, the students on the Caltech Robotics Team have been carefully crafting and optimizing their robotic submarine named Bruce—the team's entry in the 17th Annual International RoboSub Competition.

At the competition, which will take place in San Diego this week, Bruce and 38 competitors from around the world will be scored on how many tasks they can complete in 25 minutes. On their own, the tasks—pulling a lever, parking between two poles, and shooting little torpedoes at a target, for example—seem relatively simple. However, as a completely autonomous robot, Bruce is programmed to perform these tasks without the help of a human operator; when the competition begins, the team will hand Bruce over to a professional diver who will place the robot in the water and flip a switch.

The Caltech team is no stranger to competition—its robotic rover placed second in a 2012 NASA competition—but the contest this week will be Bruce's debut. And although the rookie robotic team member may get all the attention in San Diego, the 30 students who have been working to perfect Bruce are the team's real all-stars.

To learn more about Bruce—and the humans behind the robot—check out the roster of selected team leaders below:

 

Name: Bruce
Team title: robotic submarine
Year: 2014-?
Major: undecided
Summer plans: competing at the International RoboSub Competition in San Diego

A pair of unique attributes:
1. A pressurized hull. Like any watercraft, Bruce has to have a watertight body called a hull. Bruce's pressurized hull is pumped up with a bicycle pump the night before entering the water. If the pressure is the same in the morning, the team knows that Bruce is watertight and can safely enter the water without ruining expensive electronics.
2. A Doppler velocity logger (DVL). When you're driving a vehicle on land, the number of wheel rotations can tell you how fast and far a vehicle has traveled. Since this isn't possible in the water, a DVL sends out radar signals to the pool floor, measuring the Doppler shift of the return signals to determine the robot's position. DVLs are expensive, but the Caltech team was able to refurbish a broken one—a gift from a sponsor—for Bruce's upcoming competition.

 

Name: Solomon Chang
Team title: programming lead
Year: class of 2015
Major: computer science
Summer plans: interning at Google for the image search infrastructure team

What skills have you learned since joining the team?
On the robotics team, I have been able to channel the theoretical learning from my classes at Caltech into a practical form. In preparation for the competition, I've been working closely with a software team which involved working on 20,000 lines of code—something I'd never experienced in classes. Although it might sound cliché, I cannot begin to emphasize the usefulness of the robotics team in applying software concepts to the real world.

 

Name: Erin Evans
Team title: mechanical engineering subteam member/fundraising and outreach lead
Year: class of 2015
Major: mechanical engineering
Summer plans: SURF research with Professor Sergio Pellegrino in the Space Structures Laboratory

In addition to implementing a robotic submarine design, what have you learned from your time on the team?
It has been an extremely useful learning experience that has given me skills in team management, leadership, and collaborating with people with a wide range of working styles, not to mention all the technical experience I have gained from the engineering aspect of the team along the way. It's also great to work with my teammates. It is easy to see that we've grown closer through the hours and hours of work we have put into this project over the years.

 

Name: David Flicker
Team title: electrical lead
Year: class of 2015
Major: computer science
Summer plans: hardware engineering intern for Airware, a startup that makes autopilot systems

What is one of the major victories you've experienced so far with Bruce?
The greatest success for me was fitting all of the electronics into the newly completed pressurized hull. The hull was finished on a Friday, and we really wanted to try running Bruce in the water on a Sunday, so we had one day to carefully stuff the hull full of the required electronics. Besides the number of parts and connections we needed to make in that short amount of time, the "bigger" problem was that the components were all too large. We almost didn't fit the electronics inside the hull, which would have stopped us dead in our tracks—but luckily, we found a way to make it work.

 

Name: Justin Koch
Team title: project manager
Year: class of 2015
Major: mechanical engineering
Summer plans: robotics research with Disney Imagineering

What's the main thing you've been prepping in the final months before the competition?
The main thing we will be focusing on before the competition is the reliability of our system. While we won't be able to do every task, the ones we do attempt need to be consistently successful. As a rookie team, we probably won't be the best vehicle in the competition, but we will be the best at what we can do. Once we're done competing for the first time this year, we plan to return to the competition and win.

The 17th Annual International RoboSub Competition will take place July 29-August 3, 2014, at the SSC Pacific TRANSDEC in San Diego. On July 30, the Caltech Alumni Association will be hosting an event in San Diego to celebrate the team's first RoboSub competition. Find more information about the event here.

The team is advised by Joel Burdick, the Richard L. and Dorothy M. Hayman Professor of Mechanical Engineering and Bioengineering.

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Future Electronics May Depend on Lasers, Not Quartz

Nearly all electronics require devices called oscillators that create precise frequencies—frequencies used to keep time in wristwatches or to transmit reliable signals to radios. For nearly 100 years, these oscillators have relied upon quartz crystals to provide a frequency reference, much like a tuning fork is used as a reference to tune a piano. However, future high-end navigation systems, radar systems, and even possibly tomorrow's consumer electronics will require references beyond the performance of quartz.

Now, researchers in the laboratory of Kerry Vahala, the Ted and Ginger Jenkins Professor of Information Science and Technology and Applied Physics at Caltech, have developed a method to stabilize microwave signals in the range of gigahertz, or billions of cycles per second—using a pair of laser beams as the reference, in lieu of a crystal.

Quartz crystals "tune" oscillators by vibrating at relatively low frequencies—those that fall at or below the range of megahertz, or millions of cycles per second, like radio waves. However, quartz crystals are so good at tuning these low frequencies that years ago, researchers were able to apply a technique called electrical frequency division that could convert higher-frequency microwave signals into lower-frequency signals, and then stabilize these with quartz. 

The new technique, which Vahala and his colleagues have dubbed electro-optical frequency division, builds off of the method of optical frequency division, developed at the National Institute of Standards and Technology more than a decade ago. "Our new method reverses the architecture used in standard crystal-stabilized microwave oscillators—the 'quartz' reference is replaced by optical signals much higher in frequency than the microwave signal to be stabilized," Vahala says.

Jiang Li—a Kavli Nanoscience Institute postdoctoral scholar at Caltech and one of two lead authors on the paper, along with graduate student Xu Yi—likens the method to a gear chain on a bicycle that translates pedaling motion from a small, fast-moving gear into the motion of a much larger wheel. "Electrical frequency dividers used widely in electronics can work at frequencies no higher than 50 to 100 GHz. Our new architecture is a hybrid electro-optical 'gear chain' that stabilizes a common microwave electrical oscillator with optical references at much higher frequencies in the range of terahertz or trillions of cycles per second," Li says.  

The optical reference used by the researchers is a laser that, to the naked eye, looks like a tiny disk. At only 6 mm in diameter, the device is very small, making it particularly useful in compact photonics devices—electronic-like devices powered by photons instead of electrons, says Scott Diddams, physicist and project leader at the National Institute of Standards and Technology and a coauthor on the study.

"There are always tradeoffs between the highest performance, the smallest size, and the best ease of integration. But even in this first demonstration, these optical oscillators have many advantages; they are on par with, and in some cases even better than, what is available with widespread electronic technology," Vahala says.

The new technique is described in a paper that will be published in the journal Science on July 18. Other authors on this paper include Hansuek Lee, who is a visiting associate at Caltech. The work was sponsored by the DARPA's ORCHID and PULSE programs; the Caltech Institute for Quantum Information and Matter (IQIM), an NSF Physics Frontiers Center with support of the Gordon and Betty Moore Foundation; and the Caltech Kavli NanoScience Institute.

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Future Electronics May Depend on Lasers
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