Paleontology on a (very) small scale
Illustration by Andre de Loba

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Paleontology on a (very) small scale

Illustration by Andre de Loba

Our prehistoric past is a blur. Scientists are not sure, for example, exactly where the first Homo sapiens emerged around 200,000 years ago, or why our cousins, the Neanderthals, went extinct more than 150,000 years later.

On the other hand, they do know quite a bit about our immune system’s historic battles, dating as far back as 11 million years. In studying DNA of orangutans, macaques, and other present-day primates, Rockefeller biologists have revealed how our hominoid ancestors conquered a retrovirus—a pathogen of the same class as modern HIV. This fresh DNA contains ancient traces of infection: when our predecessors contracted the retrovirus, their genomes were sprinkled with clippings of its genetic material. In some cases, the infected cell happened to be a sperm or egg cell, and the imprint got passed on for generations, creating a genetic fossil record.

Gorillla Illustration

Data

The human lineage and the gorillas’ parted ways around 10 million years ago.

“Analyzing viral fossils can give us a wealth of insight into events that occurred in our distant past,” says Paul Bieniasz, who led the research, published in eLife in April. Working with scientists at the University of Glasgow, his lab has compiled a near-complete inventory of such relics within the genomes of old-world monkeys and apes, and used it to investigate the warfare between primates and their microbial enemies.

In pinpointing the precise molecular maneuvers that eventually helped our ancestors get the retrovirus out of their systems, Bieniasz and his colleagues have learned about its weak spots—insights he says could potentially be harnessed to combat modern retroviruses, including HIV.

Processing power
Photo by Mario Morgado

On Campus

Processing power

Discovery is getting data-heavy. With new tools like cryo-electron microscopy and whole-genome sequencing, even simple experiments can generate many terabytes of raw information. Rockefeller’s new high-performance computing cluster gives labs access to processing infrastructure capable of some 57 trillion calculations per second. It’s designed for the next phase of science, a future where scientists can find meaning among an unlimited number of zeros and ones.

Screen time in the aquarium
Foster, a ten-year-old Atlantic bottlenose dolphin, was one of the first to interact with an underwater touchscreen. M2C2 Research Collaborative.

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Screen time in the aquarium

Foster, a ten-year-old Atlantic bottlenose dolphin, was one of the first to interact with an underwater touchscreen. M2C2 Research Collaborative.

We know dolphins are smart, but will they use an iPad? Yes, scientists have discovered: with an underwater touchscreen built especially for them, and a little bit of training, our aquatic peers will even enjoy a game of Whack-a-Mole.

Rockefeller scientists, collaborating with colleagues at Hunter College and the National Aquarium in Baltimore, have used advanced optical technology to develop the first touchscreen computer through which dolphins can interact. Neurophysiologist Marcello O. Magnasco, who led the work, says the device allows dolphins to make deliberate choices, and can be used to study certain aspects of dolphin intelligence, including the animals’ vocal learning behavior and their ability to communicate with symbols.

“It has always been hard for humans to keep up with dolphins,” Magnasco says, “but this system will help us follow them in any direction they take us.”

Magic bullets in the blood
Zika-tainted blood samples were collected from residents of Pao da Lima, Brazil (above) and Santa María Mixtequilla, Mexico. Photo by Albert I Ko / Yale University

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Magic bullets in the blood

Zika-tainted blood samples were collected from residents of Pao da Lima, Brazil (above) and Santa María Mixtequilla, Mexico. Photo by Albert I Ko / Yale University

soon three years will have passed since the current Zika epidemic broke out in Brazil. During this time, expectant parents on several continents have been at the mercy of insect sprays and nets, and will remain so for the time being. There are no treatments or means of prevention for this mosquito-borne disease, which causes brain defects in children born from infected moms.

But scientists now have fresh optimism, incited by a discovery reported in Cell in May. In blood samples from Zika-infected donors, they’ve found what could become a potent weapon against the disease: antibodies that can neutralize the virus. And they have already initiated work to develop Zika-prevention drugs based on these antibodies—work that’s being led by Davide F. Robbiani, a research associate professor in Michel C. Nussenzweig’s lab.

The gene that keeps you up at night
Illustration by Jasu Hu

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The gene that keeps you up at night

Illustration by Jasu Hu

at 11 p.m., there’s barely enough time to get a good night’s sleep before the alarm goes off. Also, there’s Netflix, online shopping, and e-mail.

It turns out that many of us are biologically destined to be night owls. Scientists have discovered a common mutation that slows people’s circadian rhythm, the molecular clock that helps the body know what time it is, causing them to stay alert way past their supposed bedtimes.

The findings were reported in Cell in April by research associate Alina Patke and Michael W. Young, who won a Nobel Prize this year for his decades of work on sleep-wake cycles (see Interview with Michael W. Young). Collaborating with a sleep clinic, Patke and Young discovered the mutation in a patient whose internal clock was running late, a condition known as delayed sleep phase disorder. In scouring public databases, they later identified close to 30 people with defects in the same gene, called CRY1—and sure enough, all turned out to have the disorder.

Night owls won’t necessarily benefit from knowing they have the CRY1 mutation, but the researchers say its discovery may advance research on sleep disorders, and maybe lead to therapies.

Half-human, half-viral: A hybrid weapon against dangerous microbes
Large immune cells, shown in red, have been summoned by lysibodies to engulf Staphylococcus aureus bacteria (green dots).

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Half-human, half-viral: A hybrid weapon against dangerous microbes

Large immune cells, shown in red, have been summoned by lysibodies to engulf Staphylococcus aureus bacteria (green dots).

hostile germs are everywhere—in airplanes, on doorknobs, in our stomachs—and they may spread unpleasant diseases like salmonella, tuberculosis, or worse. Yet most of us have no reason to panic. The immune system is keeping us relatively safe.

The system has room for improvement, however: every once in a while, an unwelcome pathogen will let itself in. Among its flaws is the inability to spot molecules called carbohydrates, which bacteria surround themselves with. If it weren’t for this blind spot, the immune system would have more ways to catch unwanted trespassers: a bacterium dressed up in certain carbs would be parading a bull’s eye before it.

90,000

Data

Number of Americans infected with drug-resistant Staph superbugs each year.

Rockefeller scientists have engineered a molecular hybrid they hope will give the immune system some pointers, directing it toward dangerous bacteria it may not otherwise see. The agent, called a lysibody, is a cross between a viral molecule and a human one.

Some viruses that prey upon bacteria produce enzymes that bind tightly to specific carbs in a bacterium’s outer shell. In creating the lysibody, Vincent A. Fischetti and his team borrowed this function from a virus; the molecule’s lysin part latches on to the invading pathogen while its human part activates the immune system.

The researchers have successfully used lysibodies to treat mice infected with Staphylococcus aureus “superbugs” that antibiotics cannot beat, and they are now planning clinical trials to find out if these molecules could be used to treat similar infections in people.

“The approach could make it possible to develop a new class of immune-boosting therapies,” says Fischetti—therapies that potentially could be used against any disease-causing pathogen, be it a bacterium, virus, parasite, or fungus.

Shortest way to  the fruit tray?  Fly straight, turn left, and dive.
Groups of neurons in a fly’s brain (colors) compute the direction of its head as it moves.

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Shortest way to the fruit tray? Fly straight, turn left, and dive.

Groups of neurons in a fly’s brain (colors) compute the direction of its head as it moves.

all animals have an internal compass. If you close your eyes and turn around, you’ll probably still have a sense—without looking—of which direction you’re facing. Even the humble fruit fly excels at this test, making it a neat tool for scientists who study how the brain navigates.

In experiments described in Nature in May, Gaby Maimon and his colleagues challenged flies with direction-finding exercises while imaging their brain cells, leading them to discover a group of neurons tasked with updating a fly’s compass as it turns. “Our findings may have relevance for understanding spatial cognition in larger brains—including, perhaps, our own,” Maimon says.

The secret code of aerial particles
Volunteers sniffed vials containing everything from vanillin to stinky-cheese molecules. Photo by Zachary Veilleux

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The secret code of aerial particles

Volunteers sniffed vials containing everything from vanillin to stinky-cheese molecules. Photo by Zachary Veilleux

sights and sounds are unfailingly predictable. The laws of optics ascertain that when a human eye meets light with a wavelength of 470 nanometers, it will see blue. Acoustics principles are equally precise: middle C will ring in any ear subjected to a 261.6 hertz sound wave.

What about smells?

In theory, they too could be forecast based on the chemical structures of molecules that waft into the nose. But currently, we don’t know how to make such calculations; the only way to tell if a substance will smell like roses or turpentine—or to even know it has a smell—is to actually inhale it.

Scientists have taken the first steps toward making odors more calculable, however. Earlier this year, the neuroscience lab of Leslie B. Vosshall, Robin Chemers Neustein Professor, reported in Science that they had procured smell data on close to 500 molecules—the largest collection of its kind—and used it to create a prediction algorithm.

It took a village. Close to 50 volunteers came to the lab to sniff the molecules and note their characteristics and intensities. The Rockefeller team then handed this data over to collaborators at IBM, who organized a crowdsourcing contest: computer scientists from around the world were asked to build models that associate the human data with chemistry parameters.

The resulting algorithm is a blend of several winning solutions. It needs more work, but the scientists hope it will eventually open a window into the poorly understood biology of olfaction, allowing them to study how brain signals get triggered when molecules interact with smell receptors. Thus far, the tool is the furthest anyone has come in computing smells—and it’s already quite good at guessing some odors, like garlic and fish.

Fleeting Beauty

Snapshot

Fleeting Beauty

swimming bacteria produce hypnotic vortex patterns, but only when they’re moving with the right amount of vigor. Too fast, and the meticulous choreography will disintegrate into dull turbulence. Rockefeller fellow Tyler Shendruk, a physicist, discovered a mathematical signature that describes the shift from orderliness to chaos. In this image, his model simulates bacterial movement through a narrow conduit.

David Rockefeller’s passion for science—and small living things
David Rockefeller catching beetles. Courtesy of Rockefeller Archive Center

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David Rockefeller’s passion for science—and small living things

David Rockefeller catching beetles. Courtesy of Rockefeller Archive Center

For 75 years, David Rockefeller was the leading force behind the institution that bears his family name. He was a keen and influential benefactor, a visionary leader, and a regular presence on campus. Although his death on March 20, at the age of 101, deprives the university of its most steadfast supporter, David’s impact is indelible: his dedication to excellence has shaped several generations of Rockefeller scientists, and will reverberate across campus for decades to come.

In addition to being an astute businessman, a New York City developer, and a promoter of the visual arts, David was an amateur entomologist. In his spare time, he collected beetles. Among his bequests is a collection of 75,000 specimens, delicately filed inside custom-made cabinets. 

Live-cell imaging in your pocket
Photograph by Mario Morgado

Science gadget

Live-cell imaging in your pocket

Photograph by Mario Morgado

Sometimes the view through a microscope is too good to keep to yourself.

Fortunately, it turns out that smart phones, with their integrated cameras and high-resolution screens, make pretty good devices for sharing microscope images—all you need is the right adapter to align the optics.

Du Cheng, a Rockefeller M.D-Ph.D. student, has created just such an adapter. He made his first prototype out of styrofoam while still an undergraduate. At the time, it was a struggle to work the awkward bolt-on cameras attached to classroom microscopes.

Since then his devices, which he calls LabCams, have evolved into molded plastic shells with integrated eyepieces, custom-designed for several models of iPhone. The contraption can dock to nearly any microscope. Once in place, the phone’s camera takes over, providing crystal-clear, recordable views of worms, flies, bacteria, tissue samples, or any other diminutive object a biologist might be interested in. No squinting required.

Cheng and his labmates rely on the LabCam to document the behavior of the tiny nematode worm C. elegans, but a growing community of users on and off campus have captured images of everything from stem cells to rat sperm. They’re even co-opting apps like FaceTime to share findings in real time.