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Bright young minds: meet 10 scientists who are making their mark.

Just as in baseball, politics and Hollywood, science has its up-and-coming stars. They just don't always get as much publicity as, say, Bryce Harper or Lupita Nyong'o. Most scientists are lucky to get a media mention as a name attached to a discovery. But their personal stories and change-the-world goals are worth some attention.

To identify some of the early-career scientists on their way to more widespread acclaim, Science News surveyed 30 Nobel Prize winners to learn whose work has caught their attention. From those names, Science News editors chose 10 to feature in this special report. All have demonstrated high-caliber research leading to noteworthy achievements.

The good news is our list could have been longer. The researchers on these pages are representatives of a much greater number of young people likely to turn up prominently in a future issue of Science News as they pursue a diverse array of ambitious research questions.

Editing DNA

Feng Zhang, 33



Like every other 12-year-old who saw the movie Jurassic Park, Feng Zhang was awestruck by the dinosaurs. He was even more amazed by the power of molecular biology.

Now, two decades later, Zhang has developed tools to harness some of that power by controlling cells for specific purposes. As a graduate student at Stanford, he found ways to insert the gene of a light-sensitive protein found in algae into nerve cells.

The method, now part of the field known as optogenetics, made it possible to control brain cells in mice with laser light. More recently, Zhang has developed a system to easily and precisely "edit" genomes.

Zhang holds appointments at the Broad Institute of MIT and Harvard and is an investigator at MIT's McGovern Institute for Brain Research. Born in China, he moved to Des Moines, Iowa, at age 11. A year later he saw Jurassic Park during a Saturday class on molecular biology. Zhang's teacher noticed his excitement and later helped him get a volunteer position in a local lab that was researching gene therapy. Throughout high school, Zhang went to the institute every day after school and worked with molecular biologists, an experience that shaped his interest in biology.

After high school, Zhang studied chemistry and physics at Harvard, "fields that serve as a foundation for medicine," he says. He also worked in two biology labs, focusing on the structure and manipulation of viruses.

"People were using viruses as delivery vehicles to put genes into patients, so I was very interested in learning about viruses," he says.

Zhang also became interested in neuroscience. He completed his graduate work with Stanford's Karl Deisseroth who, along with Ed Boyden, was developing a method for studying the brain by controlling its activity with light.

After graduate school, Zhang set out to find more efficient ways to introduce light-sensitive proteins into specific cells. In 2013, he developed a gene-editing tool that employs the DNA-cutting microbial enzyme Cas9 to snip or swap sections of DNA exactly where needed. The tool is simpler to use than other gene-editing techniques, and Zhang's group has made it widely available.

By altering cells in mice to mimic the mutations found in human patients, Zhang's group is exploring autism spectrum disorder and related conditions. His aim? Better treatments, powered by molecular biology.--Susan Gaidos

Erasing fear memories

Steve Ramirez, 27



If not for a broken piece of lab equipment and a college crush, Steve Ramirez might never have gone into neuroscience. As an undergraduate at Boston University his interests were all over the place: He was taking a humanities course and classes in philosophy and biochemistry while working several hours a week in a biology lab. When the lab's centrifuge, a device that spins liquids, broke, Ramirez had to use one in another lab.

"I was trying to make small talk with this girl who was using the centrifuge, 'What's your major?' kind of thing," Ramirez recalls. Hearing of his myriad interests, the student suggested that Ramirez talk with neuroscientist Paul Lipton. That led to a conversation with Howard Eichenbaum, a leading memory researcher.

Eichenbaum told him that everything Ramirez was interested in was about the brain. "Everything from the pyramids to putting a man on the moon, it's all the product of the human brain, which is kind of crazy when you think about it," Ramirez says.

Studying "the most interdisciplinary organ in existence," as Ramirez calls it, was a natural fit. While working in Eichenbaum's lab, Ramirez got turned on to how the brain forms memories. Those explorations led to a Ph.D. program at MIT in the lab of Nobel laureate Susumu Tonegawa, where Ramirez focused on the individual brain cells that hold specific memories.

In a seminal experiment, Ramirez, Xu Liu and colleagues manipulated the memories of mice. The researchers first engineered the mice so their memory-forming cells would respond to light. Then the mice spent time in a box where they experienced a mild electric shock. When the mice were moved to an ordinary box, the researchers stimulated their memory cells with a laser, activating the memory of the shock; the mice froze in fear in the harmless box.

The work marks an important first step toward being able to manipulate memories in people--for example, erasing the fearful memories that are the fabric of posttraumatic stress disorder and other maladies. For now, Ramirez, who recently defended his Ph.D. thesis and is a fellow at Harvard, is focused on figuring out where in the Boston area he'll be setting up his own lab.

Wherever he lands, teaching will be a central part of his work. "The word 'professor' comes from 'declare publicly,' " he says. "We should see it as a privilege to be in the ranks of those who get to declare their work publicly."

Ramirez is passionate about openness and collaboration in research, too. "People are too guarded with their work," he says. "Science is about standing on each other's shoulders."--Rachel Ehrenberg

Caption: The red cells in this mouse hippocampus were genetically manipulated to turn on with brief pulses of light. They store a false fear memory.

Finding cancer via altered genes

Isaac Kinde, 31



Isaac Kinde became interested in medicine in elementary school. On Sundays, his father, a large-animal veterinarian, brought Isaac to work. "Seeing what disease could do to animals got me interested, piqued my curiosity," Kinde says.

Kinde is chief scientific officer at PapGene, a small biotechnology startup in Baltimore founded in 2014. The company is producing advanced technologies to detect cancer before a tumor can cause symptoms or be picked up by an imaging scan. Kinde's work is inspired by a simple idea: Cancers are much easier to treat when detected early. And that can translate into fewer deaths.

PapGene's technologies identify mutated genes associated with cancer in a Pap test, the traditional screen for cervical cancer that inspired the company's name. PapGene's method can use DNA isolated from fluids used in the Pap test to screen for ovarian and uterine cancers. Similar tests could screen blood or other fluids for genes involved in other cancers as well.

PapGene's sensitive technologies are based on tests Kinde helped develop as a graduate student at Johns Hopkins University, where he studied with cancer researcher Bert Vogelstein. Spotting cancer early requires finding a few rare, cancer-associated genetic alterations among large amounts of normal DNA. That's made more difficult by the DNA reader's error rate. Kinde and colleagues created a way to chemically label and mass-copy sections of DNA to identify the real mutations.

"He's not only devised a technology that is groundbreaking in terms of its ability to detect rare mutations ... he's also been able to implement that technology and show that it can be useful ... in patients," Vogelstein says.

Kinde, who received his M.D. and Ph.D. at Johns Hopkins, says he's most excited about improving cancer treatment through research. He discovered his passion for the lab as an undergraduate in the Meyerhoff Scholars Program at the University of Maryland, Baltimore County. Kinde says that the program, which supports diversity among scientists, had a big impact on him and his younger brother Benyam.

Kinde also credits his supportive family and years of hard work for his scientific success. His tenacity is probably fueled by his active lifestyle--he's an avid biker--and his devotion to coffee, which he says is rooted in his family's Ethiopian culture. "It's almost in our blood. I can't literally say that, because I'm a scientist," Kinde says. "But, almost." --Sarah Schwartz

Caption: Isaac Kinde's test found several gene mutations in Pap test samples from 14 women with uterine or ovarian cancers but no mutations in those genes in 14 women without cancer.


Gene expression and Rett syndrome

Benyam Kinde, 27



Many people view the brain as the last frontier of human health research, says Benyam Kinde. "We still don't know very much about how individual cells in the brain coordinate the activity of higher-level function that defines us as humans," he says.

This mystery is one that Kinde, an M.D. and Ph.D. student at Harvard Medical School and MIT, aims to solve. He is interested in how chemical modifications of DNA affect brain function, focusing on a protein nicknamed MeCP2. When this protein is damaged or missing, it changes the activity of multiple genes and causes Rett syndrome, a disorder marked by developmental delays, seizures and autism-like behaviors.

When MeCP2 grabs onto DNA, it can limit the activity of genes to which it attaches. Kinde, along with former postdoctoral researcher Harrison Gabel and colleagues, went looking for common features in genes controlled by MeCP2 and those altered by the protein's absence. In June, the researchers reported that MeCP2 prefers to attach to a specific cluster of DNA and chemicals found mainly in the brain. The genes that MeCP2 normally turns down are longer than average, and are most active in brain cells. In Rett syndrome, when MeCP2 is reduced, these long genes are overactive. Kinde and his colleagues found that a chemical that disables DNA-winding proteins can quiet such overactive genes. These insights could help researchers design treatments for Rett syndrome and similar developmental and autism spectrum disorders. The work appeared in Nature and the Proceedings of the National Academy of Sciences.

Like his brother Isaac, Kinde says he became fascinated with biology while watching his veterinarian father figure out why a horse or an elephant had died. "I was really interested in the investigative nature of his work," Kinde says. As a Meyerhoff Scholar at the University of Maryland, Baltimore County, Kinde got his first experience with neuroscience research and became passionate about solving medical mysteries. He credits excellent mentors, including his research advisers, Gabel and his older brother for his achievements so far.

Kinde hopes to tackle neurobiology questions in the clinic and the lab. There's a still lot to learn about how the brain develops, he says.--Sarah Schwartz

Memories mark DNA

Priya Rajasethupathy, 31



Priya Rajasethupathy's research has been called groundbreaking, compelling and beautifully executed. It's also memorable.

Rajasethupathy, a neuroscientist at Stanford University, investigates how the brain remembers. Her work probes the molecular machinery that governs memories. Her most startling--and controversial--finding: Enduring memories may leave lasting marks on DNA.

Being a scientist wasn't her first career choice. Although Rajasethupathy inherited a love of computation from her computer scientist dad, she enrolled in Cornell University as a pre-med student. After graduating in three years, she took a year off to volunteer in India, helping people with mental illness.

During that year she also did neuro science research at the National Centre for Biological Sciences in Bangalore. While there, she began to wonder whether microRNAs, tiny molecules that put protein production on pause, could play a role in regulating memory.

She pursued that question as an M.D. and Ph.D. student at Columbia University (while intending, at least initially, to become a physician). She found some answers in the California sea slug (Aplysia californica). In 2009, she and colleagues discovered a microRNA in the slug's nerve cells that helps orchestrate the formation of memories that linger for at least 24 hours.

An even more intriguing finding in the sea slug's nerve cells was piRNA, a molecule a bit bigger than a microRNA. In the presence of serotonin, a chemical messenger involved in learning, the piRNA suppresses production of a protein that hinders memory formation. Rajasethupathy and colleagues propose that the piRNA accomplishes this shutdown by indirectly altering the nerve cell's genetic instructions. By adding chemical tags to DNA, the piRNA may turn off part of the genome--and keep it off for years. This sort of epigenetic change, Rajasethupathy says, "could be a mechanism for the maintenance of really long-term memories."

Since arriving at Stanford in 2013, Raj asethupathy has begun working with mice, exploring neural circuits involved in memory retrieval. She's also looking for links between abnormal memory behavior and particular genetic mutations, with the goal of determining how those genetic changes might disrupt neural circuitry. Such findings could provide insights into neurological disorders, she says. Although she dropped her medical ambitions, Rajasethupathy says her clinical training is an asset. "Having the medical perspective broadens the scope and questions that you can think about."--Erin Way man

Caption: By observing nerve cells (shown) in sea slugs, Priya Rajasethupathy discovered small RNAs play a role in memory.

Redrawing the cells floor plan

Gia Voeltz, 43



Gia Voeltz didn't set out to rewrite biology textbooks. She just wanted to make a movie.

A cell biologist at the University of Colorado Boulder, Voeltz was studying a humble part of the cell called the ER, for endoplasmic reticulum. In illustrations, it's the pile of wavy lines floating near the nucleus.

The ER might not be as sexy as the DNA-holding nucleus, or as famous as the mitochondria, the cell's energy powerhouses. But it's no slouch. It has a respectable job storing calcium. It's a nice platform for building fats and proteins. Scientists thought they had it pretty much figured out.

But no one had really seen the ER in action. So Voeltz and colleagues made it glow green and filmed it moving inside living cells. ER tendrils zipped around the cell, the film showed. They reached every corner and crevice, clinging to cellular parts like spider webs wrapped around flies.

"All of a sudden we realized, 'Wow, everything's attached! Who would have thought?" she says. Squiggly looking webs bloom in vivid green, showing "just how beautiful the ER really is," Voeltz says. "It's so crazy dynamic and cool."

In 2011, Voeltz and colleagues showed that the ER actually clamps around mitochondria and helps them divide.

"The ER is doing way more than we ever thought," she says.

Voeltz wasn't afraid to shake things up. After working on RNA as an undergrad at the University of California, Santa Cruz and then at Yale as a grad student, she jumped into the ER field cold. A talk by Harvard cell biologist Tom Rapoport persuaded her to switch fields and work in his lab.

But Voeltz didn't know much about cell biology; she had to learn everything from scratch. She thinks that leap out of her comfort zone helped her give the ER a fresh look. "I didn't have any preconceived notions," Voeltz says.

By giving the ER such a radical makeover, Voeltz has upended the traditional view of a cell's floor plan. Textbooks should no longer picture organelles tucked away in their own private corners of the cell, she says. Rather, books should show the ER branching out well beyond the nucleus and binding cellular parts together.

Publishers are taking note. Since Voeltz reported her work, three have included her ER images in their textbooks.--Meghan Rosen

Caption: The endoplasmic reticulum (green) in this monkey cell reaches from the nucleus (lower left) throughout the cytoplasm, bound tightly to mitochondria (blue) and endosomes (red).

Error-free quantum calculations

Shinsei Ryu, 37



On the boundary between the quantum and everyday realms, things don't always make a whole lot of sense. The bundles of particles that make up materials behave in ways both unexpected and unexplained. This is the weird world that theoretical physicist Shinsei Ryu hopes to bring into focus.

Ryu ponders materials beyond the scope of classical physics at the University of Illinois at Urbana-Champaign. His research into quantum materials such as high-temperature superconductors could one day help quantum computers make error-free calculations.

Ryu's first steps into physics weren't entirely his own. While enrolled in the University of Tokyo, he chose physics as his major mostly because his college friends had. Since then, he's the only one of his friends who has never considered quitting. The excitement and mysteries of the field keep him going, he says.

In 2005, when he moved to the United States from his native Japan for a postdoctoral appointment, Ryu expected to stay "for only a few years." He quickly fell in love with the collaborative atmosphere and decided to continue his quantum career stateside.

In the materials Ryu studies, packs of electrons interact in surprising and bizarre ways. These interactions can create entirely new material properties such as superconductivity, in which electrons pair off and crowd into the least energetic quantum states instead of spreading out. The systems can be so complex that the goal isn't finding the right answers, Ryu says, "it's asking the right questions." Quantum applications such as computers rely on consistency--the same question should yield the same answer every time. Rut the quantum interactions between electrons are often unpredictable, so Ryu hunts for measurements that reliably return the same value again and again. He likens the systems to a doughnut shape. The curvature of the doughnut's surface can change when external forces press in, but the number of holes in the doughnut stays the same. These kinds of robust properties will make accurate quantum computing possible, he says.

The work can be very abstract and difficult at times, Ryu admits. At those points he leans on his background in experimental physics to stay grounded and "maintain a sense of reality."

"I'm lucky," he says. "I've had experience in multiple disciplines of physics. There's no magic to this, it's just experience." --Thomas Sumner

Looking deep into atoms' hearts

William Detmold, 40



William Detmold exposes matter at its most fundamental--with the help of some serious processing power.

The MIT theoretical physicist uses supercomputers to simulate how parcels of matter far too small to be seen through a microscope bind together to form the nuclei of atoms. His research complements findings from particle physics facilities such as the Large Hadron Collider near Geneva. Detmold's simulations could also point physicists toward undiscovered varieties of matter.

Detmold grew up in Adelaide, Australia, hooked on solving mathematical puzzles. Then he turned his attention to theoretical physics. He happened to be pursuing his Ph.D. at a time when physicists were relying on heavy doses of math to work through a key puzzle: understanding the makeup of atoms.

High school textbooks depict the nucleus of an atom as a simple repository for protons and neutrons. Rut protons and neutrons are composed of even smaller particles called quarks, which are held together by force-carrying particles called gluons. A complex set of equations within the theory of quantum chromodynamics, or QCD, describes how quarks and gluons interact. By the mid-2000s, supercomputers had finally attained enough processing power to simulate the activity of quarks and gluons within a tiny three-dimensional space over time. Physicists ran these "lattice QCD" simulations to study the structure of two-quark particles called mesons and three-quark particles such as protons.

Now Detmold is leading the charge to extend the usefulness of lattice QCD to larger chunks of matter. In a study published last year in Physical Review Letters, Detmold and colleagues simulated the quark-gluon interactions for hydrogen and helium nuclei. Similar calculations could reveal properties, such as the nuclei's intrinsic magnetism, that are difficult to measure experimentally. Any discrepancy between the computers' output and experimental measurements could signal the existence of new particles or forces.

Detmold has also explored the fundamental structure of matter not yet seen. In a pair of studies published last year in Physical Review D, he and colleagues used lattice QCD to show how particles that don't interact with ordinary matter could form "dark nuclei." These mysterious nuclei could help explain dark matter, which makes up most of the universe's mass. "I'm interested in describing stuff we know is there," Detmold says, "but also using those same tools to look beyond."--Andrew Grant

Caption: Detmold illustrates neutrons (blue) and a proton (orange) inside an atom's nucleus. The arrows show the alignment of the spins of each particle.

Better synthesis of natural compounds

Sarah Reisman, 36



Organic chemistry haunts most pre-med students, but not Sarah Reisman. The two-semester class was so invigorating that she abandoned her pre-med major to pursue chemistry.

"Organic chem presented me with this idea that we could do things that are new," says Reisman, who heads a lab at Caltech. "The idea that I could design a brand new way to make a molecule, there was this real creative component," she says.

Reisman got the science bug in high school through a program that paired local students with scientists at the MDI Biological Laboratory in Bar Harbor, Maine. As an undergraduate at Connecticut College in New London, she worked in the lab of chemist Timo Ovaska. He asked Reisman and three other undergrads to make various fragments of the ringed molecule phorbol, a difficult task.

"We never made that molecule, but he had a plan and some naive students that were happy to try," she says. "It taught us how to think about making these products and to be ambitious." While getting her Ph.D. at Yale in the lab of John Wood, Reisman dived into synthesis strategies and new reactions, a focus that continued during a postdoc at Harvard. Today she keeps a running list of seemingly impossible-to-synthesize molecules, ones that many chemists steer clear of. "We try to look at molecules that we don't know how to make," she says. "What are the reactions that we wish we had?"

Many of these molecules are made by plants, fungi or bacteria and have interesting biological activities that could prove useful in drug development. The molecules typically have elements of asymmetry, dangling reactive chemical groups, and a backbone of many rings. (A motif that Reisman sees everywhere: "A piece of abstract art in an airport looks like benzene rings to me.")

She has already developed several new synthesis strategies, including a way to make the fungal metabolite acetylaranotin and its chemical relatives. These compounds are potential cancer therapeutics, but difficult to work with.

Without feasible ways to make these molecules, scientists can't generate quantities large enough for study. Enter Reisman."There's still so much important chemistry to do."--Rachel Ehrenberg

Caption: Structural scribbles adorn the fume hood during synthesis of a plant-derived natural product.

Creating maps in the brain

Yasser Roudi, 34



Your senses are bombarded by constant information--sounds, colors, shapes and ever-changing motion--yet you don't notice most of these things. The brain has figured out ways to pay attention to relevant information and ignore distractions.

How the brain does this is not fully understood, but physicist Yasser Roudi says one thing is clear: "It's about information processing in a very chaotic environment that's full of signals."

Roudi is figuring out how to sort through and make sense of the vast number of inputs that bombard the brain and other complex systems.

Born in Tehran, Roudi knew from an early age that he wanted to pursue physics and mathematics. While studying physics at Sharif University of Technology in Tehran, he met a teacher who introduced him to the brain and its networks of neurons. At posts in London and Stockholm, Roudi worked on applying math and physics to studies of the brain and other systems. In 2010, he moved to the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Trondheim.

Today, Roudi draws on information theory and statistical mechanics to extract meaningful information from the data deluge. He's finding ways to apply math to a messy living system, developing algorithms to draw inferences about the brain.

In 2013, Roudi's team revealed intricate details of how the brain's GPS-like neurons called grid cells form their maps, which allow animals to navigate and sense their surroundings. In some cases, pairs of grid-like cells curb each other's behavior. His group also described how signals from the hippocampus influence grid cells. The findings appeared in two papers in Nature Neuroscience.

Roudi's group is now developing automated ways to analyze even more data from complex systems and help scientists find "hidden" but important variables.

"Certainly a lot of breakthroughs in science have come through because somebody came across a cell that happened to respond to a certain thing, but not other things," Roudi says. "The signal was there, and people had been recording it, but it just didn't catch the attention that it should have."--Susan Gaidos

--SN Editors


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