Unlocking the Chemistry of Life

Scientists can easily sequence an entire genome in just a day or two, but sequencing a proteome—all of the proteins encoded by a genome—is a much greater challenge says Ray Deshaies, protein biologist and founder of the PEL.

“One challenge is the amount of protein. If you want to sequence a person’s DNA from a few of their cheek cells, you first amplify—or make copies of—the DNA so that you’ll have a lot of it to analyze. However, there is no such thing as protein amplification,” Deshaies says.

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Viral Videos (And Bacterial Ones, Too)

Grant Jensen is taking what he’s learned over the past 13 years using cryo-EM and sharing it with the world through a series of online videos that serve as visual textbooks to teach to the world the skills and knowledge needed for cryo-EM studies.

“The nature of our work is very visual,” says Jensen, a biologist who is one of just a handful of experts in this growing field, in which the electron imaging of cryogenic samples allows scientists to image biological specimens in as close to a natural, or native, state as possible.

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Three Cheers for Science

Last year, Erik Sorto (above) did something he hadn’t been able to do in more than a decade: he lifted a glass to his lips and took a sip. The feat represented an incredible advance not only for Sorto but also for neuroscience. Sorto is paralyzed from the neck down; with the help of a robotic arm and brain implants that assist him in turning his intentions into actual motions, he is now able to sip beverages, offer handshakes, and even play “rock, paper, scissors.”

“I was surprised at how easy it was,” says Sorto about the first time he was able to control a robotic limb. Sorto’s sipping success came as a participant in a clinical trial led by principal investigator Richard Andersen, Caltech’s James G. Boswell Professor of Neuroscience, who has developed implantable neuroprosthetics that create natural and fluid motions by using a person’s intent to move. The results of the trial were published in the May 22 edition of the journal Science.

“When you move your arm, you really don’t think about which muscles to activate and the details of the movement. Instead, you think about the goal of the movement. For example, ‘I want to pick up that cup of water,’” Andersen says. “So in this trial, we were successfully able to decode these actual intents, by asking the subject to simply imagine the movement as a whole, rather than breaking it down into myriad components.”

Andersen and his colleagues were able to improve upon current neuroprosthetics by implanting them in a different brain region—the posterior parietal cortex (PPC). Most current implants target the motor cortex instead. In the clinical trial—designed to test the safety and effectiveness of this new approach—Andersen’s Caltech team collaborated with surgeons at Keck Medicine of USC and the rehabilitation team at Rancho Los Amigos National Rehabilitation Center. The surgeons implanted a pair of small electrode arrays in two parts of Sorto’s PPC. The arrays were connected by cable to a system of computers that processed the signals, decoded what it was Sorto intended to do, and then sent those signals to output devices that included a robotic arm developed by collaborators at Johns Hopkins University.

Once he’d recovered from the surgery, Sorto began learning how to use his thoughts and intentions to control first a computer cursor and then the robotic arm. “This study has been very meaningful to me,” says Sorto. “It gives me great pleasure to be part of the solution for improving paralyzed patients’ lives.” —JSC

Tracking Down Infections

Today, when there is an outbreak of disease, the first reports of it are likely to be online, through Facebook or Twitter. And as word in cyberspace goes viral, it can map closely to the spread of the actual virus in the physical world. That’s the conclusion of NYU researcher Rumi Chunara (BS ’04), whose paper analyzing Twitter and other online activity surrounding the 2010 outbreak of cholera in Haiti made waves in the public health world.

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Need a Drink?

After taking your dog for a run on a warm sunny day, it’s likely that your first instinct upon returning home is to gulp down a whole glass of water. Fido slurps from his bowl, too, as you’re both driven to the same specific behavior by a signal that the body’s healthy ratio of salt to water is getting out of balance. But how does that signal result in the desire to drink water? Assistant Professor of Biology Yuki Oka has pinpointed specific neurons in the brain that control this response, at least for mice.

Oka and his colleagues focused a recent study on the circumventricular organs—the regions related to the hypothalamus that were previously suggested to play a role in thirst. Using optogenetics, a technique that allows the control of neural activities with light, the researchers found two distinct populations that controlled the animal’s water-drinking behavior. When the researchers “turned on” the first group of neurons, it evoked an intense drinking behavior even in fully water-satiated mice. The activation of a second group of neurons, on the other hand, could block the desire to drink even in highly water-deprived animals.

Although the work was done in mice, Oka says the finding suggests that there are innate brain circuits that can act as “switches,” creating or erasing the desire to drink water—and that these circuits could act as a thirst control center in humans, too.

–Written by Jessica Stoller-Conrad

Header photo courtesy of Susan Schmitz/Shutterstock.com

The Sounds of Science: The Brain Imaging Center

“It sounds kind of like a cross between a car alarm and an angry squirrel, with some drums in the background.”328-audio-icon

 Ralph Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology, describes the sound of the pulse sequence used for functional imaging of the human brain at Caltech’s Brain Imaging Center.

Header photo by Caltech Conte Center

X-Ray Vision

In the past, the calculations needed 
to interpret X-ray diffraction patterns and solve molecular structures were the most time-consuming part of crystallography. Now, X-ray technology is constantly improving, with better detectors and with beams that can be controlled with greater and greater precision, allowing researchers to analyze bigger and more complex structures. Computers now take less than a second to do the math that once took weeks 
by hand. These advances have made crystallography nearly limitless in its potential, Andre Hoelz says. Researchers can study as complex a system as they wish. “We pick a project and we make it happen,” he says.

To aid in their experiments, Caltech researchers have access to the Molecular Observatory, which includes an automated X-ray beam line at the Stanford Synchrotron Radiation Laboratory. The campus also has its own in-house macromolecular X-ray crystallography facility. The Macromolecular Crystallization Laboratory in the Beckman Institute provides automated and robotic facilities (yes, there are actual robots) to help researchers prepare their samples efficiently.

Such automated methods allow researchers to do experiments with much less sample material than before, and thus to solve more challenging problems. According to Bil Clemons, in the roughly 15 years since he started doing crystallography the amount of sample protein needed has dropped 
by about 20-fold. Still, preparing
 and crystallizing samples is laborious, and is the hardest part of crystallography today.

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 Header Photo by Thomas Spatzal and Doug Rees

Seeing Clear Through

Although the formation seen here could easily pass for a sepia-toned collection of clouds, you won’t be seeing these structures up in the sky anytime soon. The pink wisps are, in fact, fluorescently labeled intestine cells that were imaged within an intact mouse intestine—a feat made possible by a new technique developed by researchers in the lab of Viviana Gradinaru (BS ’05), assistant professor of biology. With this method, researchers can now make thick masses of tissue samples—such as organs and even entire organisms— almost completely see-through, a capability that has numerous research and clinical applications. Rather than having to physically slice through tissue, image each thin slice, and then digitally reconstruct the images into a 3-D visualization of the cells in an organ, researchers using Gradinaru’s technique can bypass these time-consuming steps by applying a solution of detergents to whole organs or organisms. The detergents dissolve light-blocking lipids in the cells, while the structures remain intact thanks to a supporting hydrogel that the researchers embed throughout the tissue—meaning that it becomes possible to look directly through and locate specific cells.