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Robobugs, Gecko Tape, and Nature's Inspiration

The National Academies named Robert Full a National Academies Education Mentor in the Life Sciences 2005-2006. (Photo ©2000 Peter Menzel, from Robo sapiens: Evolution of a New Species (MIT Press))

In the last four billion years, Mother Nature has evolved some amazing feats in engineering. That's why UC Berkeley professor Robert Full spends so much time studying how cockroaches, crabs, lizards, and other creepy-crawlies move through the world. His groundbreaking research on animal locomotion not only deepens our understanding of biology but has also inspired such wonders as a mechanical crab, robotic cockroach, and self-cleaning adhesive tape based on a gecko's foot.

"Our motto is 'diversity enables discovery,'" says Full, a professor of integrative biology. "We look at a very diverse group creatures and see if we can extract principles from them that engineers can use to build things that weren't possible before."

Full's laboratory looks like a gymnasium as imagined by the animators of A Bug's Life, an animated film that Full consulted on. Centipedes and rhino beetles run in place while high-speed videocameras capture their gaits at 1,000 frames per second. (Years ago, the researchers were surprised to find that nearly every animal they studied moves with the same bouncing pattern as humans.) A highly-sensitive scale measures the force of a carpenter ant's step. A vertical, clear treadmill, dubbed the "geckomill," enables the researchers to closely observe how a gecko's foot firmly attaches and then peels off a smooth surface.

A centipede on a treadmill

Full put a centipede through a treadmill workout. (Photo ©2000 Peter Menzel, from Robo sapiens: Evolution of a New Species (MIT Press))

"We also study animals at the extremes of performance, creatures that are exceptionally good at one particular thing," Full says.

For example, Full has long been intrigued by the millions of microscopic hairs on a gecko's toes that act as an incredibly-strong adhesive, providing them with their climbing prowess. Indeed, Full is actively working with several engineers, including Berkeley's Ron Fearing, to develop an artificial gecko adhesive comparable to its natural inspiration. The material could be used in everything from robotics to a new kind of Band-Aid.

Most recently though, Full and his students have been helping Stanford University professor Mark Cutkosky and University of Pennsylvania professor Daniel Koditschek build robots that can climb walls. In the future, these mobile robots might seek out survivors in buildings submerged during a flood or search for hidden explosives in the rubble of war zones.

The RHex robot, built by the University of Michigan

Inspired by Full's discoveries about how cockroaches run, the RHex robot was built at the University of Michigan. (courtesy Daniel Koditschek, University of Michigan)

"Again, we looked at the world's greatest climbers, the Geckos," Full says. "At first, we thought it was just the amazing foot that enables them to grab onto anything. But as we worked with the engineers while they were building the robot, we found some general patterns of movement in the legs of Geckos and insects that we hadn't seen before. So Mark and his team put them in the robot."

The resulting shoebox-size robot doesn't resemble a lizard or a bug, but it can easily scurry up and down a tree or concrete wall. Arrays of tiny spines on the robot's feet catch on to microscopic rough spots on the wall. Those spines combined with the carefully choreographed motion of the feet and limbs inspired by Full's animal studies enable the robot to get a good foothold without sacrificing speed.

"It doesn't look like any real animal, but all of the principles are there," Full says.

As the engineers fine-tune their robot, they're also providing feedback to Full on what his group may look for in their own research. For example, the robot's stability is dependent on a "tail" structure that the Stanford team added. Full says his group will look at their animals to determine why this may be necessary. In fact, he says this cross-pollination of ideas across disciplines, from biology to mathematics to engineering, is the key to progress.

A robot that can climb a tree

Full's discoveries also inspired the design of the climbing robot RiSE built in collaboration by Stanford University, the University of Pennsylvania, and Boston Dynamics. (courtesy the researchers)

"Everyone can advance their own field, but through synergy, the research accelerates and collectively we can create something that no single group could ever do," Full says.

This multidisciplinary approach is at the heart of a new Berkeley research center Full is directing. CIBER is a dual acronym, he explains, standing for both the Center for Integrative Biomechanics in Education & Research and also the Center for Interdisciplinary Bio-inspiration in Education & Research. The former references the research focus of this particular center. The latter name, Full explains, is a call for a new paradigm where research and education are inseparable. Only if students actually work together across disciplines on real world problems can they ever hope to truly learn from nature and surpass her in our applications, he says.

"Evolution works on the just-good-enough principle," Full says. "So we want to learn how to mesh advantageous principles from biological systems with the best human engineering to actually build things that are better than nature."

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Spinning Out the Future of Computing

The computer industry is headed toward a brick wall. Within a decade or so, Moore's Law–which predicts that the number of transistors that can be packed on a silicon integrated circuit doubles every 18 months–will run up against the laws of physics. To keep processing speed on the ever-increasing fast track, scientists and engineers are experimenting with entirely new kinds of devices that could be the building blocks of tomorrow's computers. UC Berkeley physicist Joe Orenstein's research is in the realm of "spintronics," a field that could lead to computers that store and process information in the spins of individual atoms.

portrait of Joe Orenstein

Joe Orenstein, shown here with a grating used in spin spectroscopy, is an expert at employing electromagnetic radiation to probe condensed matter systems. (photo Roy Kaltschmidt, CSO)

"Chip companies are feeling the pressure of Moore's Law," says Orenstein, who is also affiliated with Lawrence Berkeley National Laboratory's Materials Sciences Division. "They're looking for what's next, and spintronics is certainly under consideration."

The angular momentum carried by an electron is referred to as electronic spin. An electron's spin is similar, at least conceptually, to the direction of a rotating top. Labeled "spin-up" or "spin-down," an electron's spin can be used to represent a zero or one, much like a charge of voltage in a traditional transistor. At this small scale though, so-called "quantum weirdness" comes into play. Spin can be actually be "spin-up," "spin-down," somewhere in the middle, or, oddly, both at one time.

That's why if spintronics can be made to work, Orenstein says, the direction of an electron's spin would "make the perfect qubit," or building block of a quantum computer. Each qubit could represent multiple values at the same time. As more qubits are strung together, the power of the quantum processor grows exponentially.

Meanwhile, certain kinds of spin current, generated as electrons move through a semiconducting material like silicon, may dissipate less energy than the charge current of today's transistors. So even if quantum weirdness can't be harnessed to build a quantum computer, spintronics could still help prevent microprocessors from overheating so easily.

"As a practical matter though, can we create currents of spin, store spin, and change spin?" Orenstein says. "And if so, can we detect it? Those are all open questions."

diagram of electronic spin

Electron spin is assigned a value of "up" or "down." (courtesy Berkeley Lab)

Recently. Orenstein and his colleagues took a leap forward in uncovering the secrets of spin currents. Specifically, the researchers demonstrated that compared to charge current, spin current moves through the semiconductor at a slower rate. The effect, called "spin Coulomb drag," is caused by the electrons bouncing into each other as they move through the material.

Spin Coulomb drag was first posited in 2000 by scientists at the University of Missouri. The theory wasn't well-received and Orenstein's group hadn't even heard of it when they began their research. Through a series of novel experiments though, Orenstein and his team proved that the 2000 theory was right on target.

"We learned something very definite and concrete at the end of the day," he says.

To conduct their experiments, Orenstein and his colleagues modified a tried-and-true technique called transient grating spectroscopy. They point two lasers at a sample of electron gas held in "quantum wells" of gallium arsenide. The lasers pulse at one-tenth of a picosecond, creating alternating layers of electons with different spin states. Over time, the bands of spin-up and spin-down states blur into each other. The resulting pattern is then "read" by two other lasers. This provides the researchers with the "spin diffusion coefficient" that can be used to calculate the drag on the collective motion of the electrons.

Whether these new findings will hinder or accelerate the development of spintronics-based computers depends on the particular architecture of the processor, Orenstein explains. When high-speed flow of spin current is essential, the drag would be, well, a drag. But if the system calls for the spins to remain isolated for long periods, spin Coulomb drag might be a feature rather than a bug.

Still, the future of spintronics-based computers is far from a certainty. Right now, the experimental devices can only operate at incredibly cold temperatures to prevent the fragile electron spin states from changing willy-nilly. To that end, Orenstein is collaborating with UC Berkeley chemistry professor Peidong Yang to determine whether nanowires, thousands of times thinner than a human hair, could be used to reign in the electrons so their direction could be better controlled.

"With this kind of tabletop science, each day presents the opportunity for discovery, which is different from experiments where the apparatus may take many years to build," Orenstein says. "It's possible to learn things about matter that aren't relative or subjective but can actually be proven to be absolute truths."

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Engineering Evolution

David Schaffer comes from a medical family, with parents who are biomedical researchers and a sibling who is a doctor. Yet when he decided to design new techniques to tackle some of humankind's toughest diseases, he bucked the family traditions and did it his way—as a chemical engineer at UC Berkeley.

Schaffer is working to improve the delivery of gene therapies that have the potential to fight neurodegenerative diseases like Parkinson's, Lou Gehrig's disease (Amyotropic Lateral Sclerosis or ALS), and even cancer. "Chemical engineering gives us a molecular approach to problems of mass transfer and complex reaction networks," says Schaffer. "These are problems that chemical engineers are trained to solve."

Chemical Engineering Associate Professor David Schaffer has had success in developing new gene therapy tools.

Schaffer, Associate Professor of Chemical Engineering and a member of the Helen Wills Neuroscience Institute, has reported on his success in developing new gene therapy tools in the current issue of Nature Biotechnology. His coauthors include Berkeley chemical engineering graduate students Narendra Maheshri and James Koerber, and Brian Kaspar of Ohio State's Columbus Children's Research Institute.

Gene therapy involves inserting genes into cells to program them to function in ways that are critical for health—whether it is producing a chemical like dopamine that is required for normal brain function but is depleted in people with Parkinson's disease, or producing specialized antibodies to kill cancer cells.

Schaffer and his colleagues are helping overcome one impediment to gene therapy—the human immune response. The immune system is an amazingly complex and effective system for protecting our bodies against bacteria, viruses, and the illnesses they cause. Yet in some cases, the immune response can get in the way of treating disease.

A gene therapy vector is some sort of microscopic device, often a modified virus, that has been engineered to deliver genes into living cells. Schaffer has devised a technique to circumvent the immune response to potential gene therapy vectors like the adeno-associated virus (AAV), a common, though innocuous, resident of the body. Using a technique based on directed evolution, Schaffer has created new versions of AAV that are good candidates for gene therapy vectors. Better yet, he has done so by forcing the virus itself to do the work.

A graphical representation of the adeno-associated virus (AAV). Schaffer's work has led to the creation of new versions of AAV that could one day assist in gene therapy.

"It is almost impossible for a researcher like me to rationally create gene therapy vectors than can slip past the immune defenses," says Schaffer. "The beauty of directed evolution is that we can use viral evolution to generate 'designer' gene delivery vectors without having to rationally design them ourselves."

AAV consists of two genes enclosed within a ball, or capsid, of proteins. The capsid proteins are what antibodies recognize, and Schaffer's goal was to alter the capsid proteins to allow them to bypass the immune response.

Schaffer's team first mimicked evolution by creating random mutations in AAV. By introducing small variations in the genes through an error-prone polymerase chain reaction (PCR) coupled with a test tube recombination technique, the researchers created new varieties of AAV.

After reassembling the mutant viruses inside their capsids, the researchers forced the AAV strains to run the gauntlet of rabbit blood serum rich in antibodies to AAV. Only the mutant viruses good at evading the antibodies survived the serum.

After passing the viruses three times through increasingly more potent serum, the researchers isolated the survivors and subjected them to another round of PCR that introduced more mutations. Then they forced these second-generation viruses to run the antibody gauntlet again.

After two generations of directed evolution, one strain of virus was 96 times more effective as a gene therapy vector than the wild AAV in cell culture, and two evolved strains survived injection into mice harboring nearly 1,000 times the level of antibodies normally required to neutralize the wild virus.

By sequencing the survivor strains, Schaffer and colleagues discovered that the capsid proteins of the survivors differed from those of the original strain by only seven amino acid building blocks, two of which were responsible for most of the altered interaction with antibodies.

"Starting from scratch, just trying to rationally decide which two amino acid changes to make on the virus, we could have never identified these two," Schaffer said. "Instead, we used the algorithm nature created called evolution to solve the problem for us. This virus is kind of a gift from nature–very safe and efficient–but nature never evolved it to be a human therapeutic. So we had to re-evolve it for that purpose."

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