Mixed-strain malaria infections influence drug resistance

A boy awaits treatment at a malaria clinic in Myanmar. Resistance to the one remaining drug for the most lethal species of malaria parasite, Plasmodium falciparum, has emerged in Southeast Asia.

By Carol Clark

Scientists have documented for the first time how competition among different malaria parasite strains in human hosts could influence the spread of drug resistance.

“We found that when hosts are co-infected with drug-resistant and drug-sensitive strains, both strains are competitively suppressed,” says Mary Bushman, lead author of the study and a PhD candidate in Emory University’s Population Biology, Ecology and Evolution Graduate Program. “Anti-malarial therapy, by clearing drug-sensitive parasites from mixed infections, may result in competitive release of resistant strains.”

Proceedings of the Royal Society B published the research, led by the labs of Jaap de Roode, an evolutionary biologist at Emory, and Venkatachalam Udhayakumar, a malaria expert from the Centers of Disease Control and Prevention’s Division of Parasitic Diseases and Malaria.

Almost half of the world’s population is at risk for malaria, a complex disease caused by five species of Plasmodium parasites that are transmitted to humans by 30 to 40 different species of mosquitoes that all behave differently. The current study focused on Plasmodium falciparum, the most common malaria parasite on the continent of Africa and the one responsible for the most malaria-related deaths globally.

P. falciparum has developed resistance to former first-line therapies chloroquine and sulfadoxine-pyrimethamine. “We’re now down to our last treatment, artemisinin combination therapy, or ACT, and resistance to that recently emerged in Southeast Asia,” Bushman says. “If ACT resistance continues to follow the same pattern, the world may soon be without reliable antimalarial drugs.”

People infected with P. falciparum often have multiple strains of the parasite – especially in high-transmission areas such as sub-Saharan Africa where infectious mosquito bites occur frequently. Many people have developed partial immunity, making asymptomatic infections common and further complicating control efforts.

The researchers knew from previous work, by de Roode and others, that competition between mixed strains of malaria parasites in laboratory mice are a crucial determinant to the spread of resistance. “In the mouse studies we found that drug-sensitive parasites suppress resistant parasites,” de Roode says. “We also found that by clearing these sensitive parasites with drugs, the resistant parasites had a big advantage, growing up to high numbers and transmitting to mosquitoes at high rates. Ever since doing that work, I have wanted to see if the same could apply to humans.”

The researchers drew from 1,300 blood samples of untreated children with malaria from Angola, Ghana and Tanzania. They extracted DNA of malaria parasites from the blood samples and used polymerase chain reaction (PCR) technology to determine the densities of drug-resistant strains and drug-sensitive ones. About 15 percent of the blood samples had mixtures of both types.

The results showed that in mixed-strain infections, densities of chloroquine-sensitive and chloroquine-resistant strains were reduced in the presence of competitors. They also showed that, in the absence of chloroquine, the resistant strains had lower densities compared with sensitive strains.

“The results were really clear cut, which rarely happens in human studies,” Bushman says. “We found almost complete consistency between the three data sets.”

Currently, Bushman says, the tendency is to use “one-size-fits-all” strategies for controlling malaria but more tailored approaches are needed.

A strategy of mass drug administration might be effective, for example, in a place with a low prevalence of malaria and less likelihood of mixed-strain infections. That same strategy, however, might actually boost drug resistance without reducing the burden of disease in areas where most of the population is infected with multiple strains of malaria parasites.

“The epidemiology of malaria infection is different for different places and different conditions,” Bushman says. “We hope that our work will spur development of new strategies to minimize resistance while maximizing the benefits of control measures.”

More questions must be answered to guide the development of these new strategies. “As a first step,” de Roode says, “we need to determine if the observed suppression of resistance in humans also results in reduced transmission to mosquitoes.”

Another limitation of the current study was that it was focused entirely on blood samples from children that had not been treated with drugs. “We need to find out if drug treatment of people infected with malaria removes competition and gives resistance a boost, as we have found in mice before,” de Roode says.

The study was funded by the Burroughs Wellcome Fund Institutional Program Unifying Population and Laboratory-based Science, Emory University, the Association of Public Health Laboratories, the CDC and the National Institutes of Health.

Image: iStockphoto.com

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Atlanta Science Festival fosters 'small steps, big ideas'

Emory faculty and students are set to dazzle children with science demonstrations at "Physics Live!" The event will take place on Friday, March 25 from 3:30 to 7 pm in Emory's Math and Science Building. 

By Carol Clark

"Small steps, big ideas," is the theme of the third annual Atlanta Science Festival, which encourages all ages to step into a world of wonder and exploration through more than 100 events and hands-on activities in metro-Atlanta from March 19 to March 26. In fact, the party has already started via ongoing online activities, such as a chance to vote for Atlanta's favorite scientist and compose original "sci-ku" — or science-themed haiku.

About 50,000 people are expected to turn out during the eight-day festival for talks, lab tours, film screenings, participatory activities and science demonstrations. The events are set at more than 80 different venues, including the Emory campus.

"We've got a lot of fun and irreverent events, like 'The Science of Circus," and others that are more on the serious side, like a discussion on climate change," says Jordan Rose, who is executive co-director of the festival along with Meisa Salaita. "There is something for everyone, from little kids to teens, college students and adults."

A new event this year, "Sci-Cycle: A Competitive Scavenger Hunt on Two Wheels," will start things rolling on the opening day of the festival, Saturday, March 19. The Emory Spokes Council and the Emory Graduate Sustainability Group are organizing the bike adventure, to take place on the Atlanta Beltline. Participants will learn about materials science, urban foraging and sustainable practices through pedaling to various locations and performing tasks such as using a bicycle-powered blender to make a smoothie.

Also new this year is a "Science Parade," set for the final day of the festival, on Saturday, March 26, starting at the Centennial Academy in downtown Atlanta. "Everyone is welcome to join the parade," Rose says. "We're encouraging people to come dressed as their favorite scientist, or element or other science-themed character."

The half-mile parade, led by the Seed and Feed Marching Abominable band, will end at Centennial Olympic Park for the launch of the Exploration Expo, the culminating event of the Atlanta Science Festival. The free Expo includes stage performances and hands-on science activities at 100-plus exhibitor booths, including more than a dozen run by Emory faculty and students.

Highlights of this year's Expo will include a giant LEGO build of the city of Atlanta, which will be 40-feet wide upon completion. "Everyone can help assemble a bit of it throughout the Expo," Rose says.

A range of Atlanta Science Festival events will take place on the Emory and Oxford campuses, as well as the Carter Center.

"The Atlanta Science Festival is a great way to feature some of the research and discoveries that are coming out of Emory for the local community," Rose says. "It's also a great platform for Emory students and faculty to practice their communication skills for a general audience, and to engage the public in their science."

Click here for a full listing of Emory events, and details about how to join them.

Dopamine key to vocal learning, songbird study finds

"Bengalese finches are songbirds that have extremely precise singing behavior and can also refine their songs in response to auditory feedback," says Emory biologist Samuel Sober. "This provides a way for us to understand similar patterns of learning in humans." (Emory Photo/Video)

By Carol Clark

The neurotransmitter dopamine is essential to correcting vocal mistakes, suggests a study on Bengalese finches. The Journal of Neuroscience published the research, led by Emory biologist Samuel Sober, who uses Bengalese finches as a model to understand how the brain learns.

“Our experiments are the first to isolate the role of dopamine in sensory-motor learning, as distinct from the other functions that dopamine performs in the brain,” Sober says. “Bengalese finches are songbirds that have extremely precise singing behavior and can also refine their songs in response to auditory feedback. This provides a way for us to understand similar patterns of learning in humans. The ability to use auditory feedback to fix errors in behavior underlies everything from learning to speak, to sing and to play an instrument.”

The research found that a reduction in dopamine levels in a small region of the basal ganglia in the finches’ brains caused a reduction in their ability to correct vocal errors, while having no detectable effect on their ability to sing. The basal ganglia is situated at the base of the forebrain and is associated with a variety of functions, including voluntary motor movements and procedural learning.

“Some neurons send messages to the basal ganglia using dopamine,” Sober explains. “These dopamine-containing cells are some of the same neurons that slowly die off over years in patients with Parkinson’s Disease, and problems with vocal control are often observed in Parkinson’s patients. We hope that our research may help with the understanding of the role of dopamine in vocal behavior and the development of potential therapies for learning deficits.”

A great deal of scientific literature already exists on the role of dopamine in learning to associate a stimulus with a reward or a punishment. What’s much less understood is how dopamine may play a role in learning to perform a skilled behavior, such as speaking.

To conduct the experiments on the Bengalese finches, the researchers first recorded each bird singing while an occasional blast of white noise was emitted from a speaker near the cage when the bird sang within a particular range of pitches. “The finch interprets this blast of noise as an error,” Sober explains. “We measured how fast each bird changed its pitch to avoid that noise.”

A drug was then administered to the birds to lower the dopamine levels in their basal ganglia by about half and their singing was once again recorded. “We found that their ability to correct their singing in response to the white noise also went down by about half,” Sober says. “They were still able to learn from the white noise ‘mistake,’ but they were significantly worse at it.”

While the experiment demonstrates that dopamine is necessary for processing vocal errors, many questions remain. “We don’t know if reducing the level of dopamine changes the birds’ ability to detect a vocal mistake, or whether it just affects their ability to fix mistakes once they detect them, or perhaps both,” Sober says. “Our next step is to better understand, at the cellular and molecular level, how changes in dopamine affect activity in the basal ganglia.”

The research was funded by the Morris K. Udall Center of Excellence for Parkinson’s Disease Research at Emory, part of a network of centers managed by the National Institutes of Health to foster research into the causes and possible treatments for Parkinson’s Disease, and by the National Institute for Neurological Disorders and Stroke. Co-authors of the study include Emory post-doctoral fellow Li He and graduate students Lukas Hoffmann, Varun Saravanan and Alynda Wood.

Related:
Birdsong study pecks theory that music is uniquely human
Singing in the brain: Songbirds sing like humans
How songbirds learn to sing 

A scientist's view from Earth's highest mountains

"As difficult and dangerous as mountain climbing can be, it's also an absolutely wonderful experience. You have to live it to understand it," says Stefan Lutz, chair of chemistry at Emory, shown during a Denali expedition.

By Carol Clark

In December of 2012, Stefan Lutz summited the 22,841-foot peak of Aconcagua, the highest mountain in the Western hemisphere, located in western Argentina. “The view from the top was amazing. When you look to the horizon and see the curvature of the Earth, you realize that you’re in a pretty special place,” says Lutz, professor and chair of chemistry at Emory. He is also a dedicated mountaineer who will attempt to climb Mount Everest this spring.

After a few minutes spent admiring the view from atop Aconcagua, it was time to descend. Lutz and a guide maneuvered down a particularly steep section and sat down to wait for the rest of their group.

“It was a beautiful day. I remember drinking and eating a bit of food, just trying to re-energize myself,” Lutz says. “Then I noticed a man, a climber I didn’t know, standing alone, maybe 20 feet away. He just kept standing, still as a statue. It’s exhausting at that altitude and I wondered, ‘Why doesn’t he sit down?’”

Lutz mentioned it to the guide who then approached the man. “As soon as the guide put his hand on the guy’s shoulder, he collapsed,” Lutz recalls.

They gave him some water and asked, “Do you know where you are?”

“Yes,” the man replied, “I’m on Mount Fuji.”

It was clear that the confused mountaineer, a Japanese man climbing solo, was suffering acute mountain sickness. “He was in serious trouble,” Lutz says. “Luckily, some Argentine park rangers came along. They gave him bottled oxygen which helped him recover enough that he could be helped back down the mountain.”

Without the assistance of the rangers, the climber’s condition might have progressed to high altitude cerebral edema – a severe and, if untreated, fatal form of altitude sickness when capillary fluid leaks into the blood-brain barrier due to the effects of inadequate oxygen.

“That’s the highest I’ve climbed – 22,841 feet,” Lutz says. “It’s very humbling. Even a fit person moves like a turtle at that altitude.”

Bright sunshine at 3 a.m. during a Denali expedition in Alaska.

The experience was another stark reminder to Lutz, who is 46, that his passion for climbing comes with great risks along with the rewards. “It’s not about being a thrill seeker,” Lutz says, trying to explain why he climbs. “As difficult and dangerous as mountain climbing can be, it's also an absolutely wonderful experience. You have to live it to understand it. You get a high from it that stays with you.”

A native of Switzerland, Lutz grew up hiking and being in the mountains. Five years ago, he became more serious about his hobby and started a quest to climb the Seven Summits – the highest peak on each of the continents. He leaves March 26 for Nepal and a two-month expedition to climb Mount Everest. If his Everest bid is successful, it will mark the sixth of the Seven Summits for Lutz. You can follow his team’s progress on the web site of the expedition leader, International Mountain Guides.

As part of his physical conditioning, Lutz never takes the elevator as he roams around the Emory Chemistry Center. Instead, he climbs the stairs with his large, red, expedition backpack – loaded with 60 pounds of sand – strapped to his six-foot-four frame.

Lutz is a biomolecular chemist who uses protein engineering to develop catalysts for therapeutic and industrial applications. He also enjoys teaching, and takes examples from his climbing experiences into the classroom to convey some of the complex concepts in biochemistry. “Using my mountaineering experiences brings these concepts to life and gets students more engaged,” Lutz says. “Most of them have experienced at least a hint of what I talk about, like the feeling you get at higher altitudes when hiking or skiing, so they relate to it.”

Lutz’ scientific training deepens his understanding of extreme landscapes and the physical and mental processes a climber may experience. Following is a bit of Lutz’ perspective on mountaineering, in his words and photos.

Landing in Antarctica for an expedition up Mount Vinson, the most remote, and the least climbed, of the Seven Summits.

The environment of the southern polar region 

At 16,050 feet, Mount Vinson is the highest peak in Antarctica. To get there, you start with a five-hour flight on a jet plane from Punta Arenas on the southern tip of South America to an icy airfield in the center of Antarctica. Next, you get in a DC3 fitted with skis for a 45-minute flight that sets you down nearer Mount Vinson. From there, you take an even smaller propeller plan to reach the base camp.

Antarctica stores about 65 percent of all the fresh water in the world in the form of ice. You fly over an area of incredible beauty and realize that it looks the same as it did tens of thousands of years ago. No human being has touched it and many places have had no precipitation for more than 100,000 years – just snow drifts. Antarctica is the driest continent and is actually one of the marvelous, great deserts of Earth. Humidity is in the single digits and it feels like you are in an evaporator, turning into dried fruit. The temperature routinely drops to minus 40 degrees Fahrenheit. You look to the horizon and all you see is snow, and more snow, and a few rocks. It’s beautiful in its simplicity.

We were there in December, which is mid-summer in the southern hemisphere. Since we were only about 700 miles from the South Pole, bright sunshine streamed into our tents even at 2 a.m. The snow is like a mirror. You have to wear glacier sunglasses all the time or you can go snow blind within 15 minutes. Every speck of exposed skin has to be covered with a thick layer of sunblock to avoid massive sunburn. We had one team member who forgot to put sunblock on the bottom of his nose and ended up with a really painful burn of his nostrils.

Above the clouds: Lutz makes his way up the West Buttress Ridge of Denali, with Mount Foraker in the background.

The physiology of extreme cold 

Denali in Alaska is North America’s highest peak at 20,310 feet. It’s at about 63 degrees northern latitude. To reach base camp, you fly in a single-prop plane between snow-covered peaks and land on a glacier. The plane takes off and you and your teammates are now about 70 miles away from any human habitation and, basically, living in a freezer for three weeks. The average temperature is around 0 degrees Fahrenheit. Everything that you need to climb and to survive for the next 20 days is loaded into a 60-pound pack that you carry on your back and on a sled that you pull behind you, which holds another 50 pounds.

As you work your way up the mountain, your metabolism goes into overdrive to provide sufficient muscle energy and maintain body heat in the cold. That turns climbing into an all-you-can-eat contest. I switched from my normal 2000-calorie-per-day diet to about 12,000 calories per day. And I still lost 12 pounds during my three weeks climbing the mountain! Believe it or not, it’s not easy consuming this amount of calories. At higher elevations, your appetite diminishes. Food that tastes delicious at sea level suddenly becomes unappealing as your taste perception changes. Experience has taught me to leave behind my beloved salami when climbing and instead stuff my pockets with Snickers bars and chocolate-covered raisins. I ate about 25 pounds of candy during the Denali trip. 

Burning calories to generate energy and heat is an oxidation process, and the higher you go, the less oxygen in the atmosphere. To manage the extreme altitude of Mount Everest, which is 29,035 feet, most climbers use supplemental oxygen to stay warm. You can wear lots of insulating gear but if you are not getting enough oxygen to burn fuel, you still start shivering. And if shivering is not enough to warm you up, you can develop hypothermia. At the same time, you are at risk for frostbite – the result of your body saying, “I can live without my fingers and toes, arms and legs.” It pulls your blood into your core to make sure your critical organs have sufficient blood supply. That process can happen faster at higher altitude.

Roped together on Denali. "You form a unique bond with the people that you climb with, the people on the same rope as you," Lutz says.

The biochemistry of altitude sickness

The summit of Denali has 50 percent less oxygen than at sea level. Atop Everest that percentage drops to 30 percent. Even without exercising these low oxygen levels can make you feel like you’re suffocating. You start to breathe faster to take in more oxygen but with each breath, you also exhale carbon dioxide.

Carbon dioxide is part of a buffer system in the bloodstream that prevents the pH level in cells to fluctuate. All the proteins in our cells rely on steady acidity. But if you pump out too much carbon dioxide from your body, the buffer system goes haywire and you can develop a condition called alkalosis.

Respiratory alkalosis, which is a result of blood pH rising beyond the normal range, starts off as a mild headache but can quickly progress to severe head pain and nausea. Worst of all, it has little to do with fitness. I’ve seen very strong athletes crumple up with these symptoms. If untreated, you start vomiting violently, leading to more dehydration. The condition can progress to where cellular fluid starts leading from your brain, known as cerebral edema, or your lungs, known as pulmonary edema. 

Medication such as Diamox can help the body more quickly adjust to higher altitude but the best approach is to slowly and gradually hike to higher elevations. That gives your body time to acclimatize to the thin air. It’s the reason that climbers spend nearly two months at the Everest base camp before attempting to reach the summit.

Navigating ice crevices of Denali. "Fear can become your ally by keeping you focused and alert," Lutz says.

The psychology of endurance and fear 

Mountaineering is an endurance sport but only part of that is physical endurance. A majority of it comes from your head. It can take sheer willpower to keep you going when you are cold and exhausted. Your mind has to convince your body to take the next step, hour after hour, as you work your way towards a summit. On the flip side, you can have a sunny day, blue sky and no wind and know that you are going to make it. Psychologically, it’s a breakthrough moment: A feeling that no money can buy.

The summit, however, is only the halfway point. A majority of mountaineering accidents happen during the descent. People are euphoric, but also exhausted physically and mentally. You can never let down your inner guard because you’re operating in an environment with little room for error. All it takes is one misstep.

Fear can become your ally by keeping you focused and alert. I remember traversing a narrow section on Denali called the Windy Corner. To one side of you is a rock wall. On the other side are ice crevices big enough to swallow a school bus. Rocks the size of fists fall from that rock wall and you have to dodge them almost like you are in a computer game. If a rock hits your lower body it can shatter a bone. If one hits you on the head, it can kill you. Getting through there only took a few minutes but it’s an experience that I won’t forget.

Fear can also give you strength. While climbing in the Denali range, we were roped together in groups of four as a safety precaution due to all of the crevices. One moment we were moving through a snowy glacier landscape. The next moment, one of our team members in the group just ahead of mine simply disappeared. There was no sound, just the sight of the rope running. His body had broken through a bridge of thin snow and was plummeting into a dark abyss in the ice. The team members he was roped to immediately dropped to the ground and anchored their axes into the ice to stop the fall. They then used the rope and their gear to quickly build a pulley system and extract our comrade from the crevice. After about 20 minutes of hard work by the team he was back on the glacier surface, shaken but unhurt. You would think they would be too fatigued from climbing to respond so quickly and energetically, but in a situation like that your heart rate spikes and your adrenaline level goes through the roof.

Lutz, in yellow parka, enjoys a brief celebration with teammates after they reached the summit of Denali. "These are the kinds of friendships that last forever," he says.

The sociology of bonding during intense experiences 

You forge a unique bond with the people that you climb with, the people on the same rope as you. You’re putting your lives in one another’s hands.

On Aconcagua, two of my teammates and I were crammed into our small tent one night when a ferocious blizzard hit, with winds up to 80 miles-per-hour. Nobody wants to be out in that kind of weather. Yet, every hour or so, one of us had to crawl out and dig out the tent so we would not get buried in snow. We took turns shoveling. Meanwhile, the two inside the tent made sure they had a hot drink ready when the other one finished a round.

Pulling together as a team to overcome tremendous challenges, in spite of everyone being mentally and physically exhausted, builds deep camaraderie. These are the kinds of friendships that last forever.

Related:
How a hike in the woods led to a math 'Aha!'
The math of rock climbing
Proving math is good for endurance sports

All photos by Stefan Lutz or courtesy of Stefan Lutz.

Climate-smart agriculture still lags after Paris

Nitrous fertilizer usage in agriculture generates emissions of nitrous oxide — one of the least-known, yet important, greenhouse gases.

Eri Saikawa, Emory assistant professor of Environmental Sciences, led a delegation of Emory students to the recent United Nations climate talks in Paris (COP21). An expert on greenhouse gas emissions, Saikawa wrote an opinion piece at the conclusion of the talks for The Conversation. Following is an excerpt of her article:

"Although the COP included initiatives targeting air pollution, climate and health all at once, there was a lack of comprehensive strategy for the interlinked effects of climate and agriculture at the summit.

"Agriculture contributes 10%-12% of global anthropogenic greenhouse gas (GHG) emissions, and it has altered all of the three important greenhouse gases linked to terrestrial sources: CO2, CH4 and nitrous oxide (N2O). The flip side is that there is a significant potential in agriculture for reducing these biogenic sources of greenhouse gases.

"The agricultural sector is also important because we need to pay more attention to nitrous oxide – possibly the least-known important GHG. N2O is not just a GHG; it also depletes the ozone layer in the stratosphere.

"The Montreal Protocol, which was ratified in 1989, has been effective at reducing greenhouse gases that are also ozone-depleting substances (Velders et al, 2006). However, N2O is not included in the Montreal Protocol, and its emissions are sharply rising.

"The concentrations of N2O in the atmosphere are increasing rapidly and we find that there is a statistically significant increase in emissions from the agricultural sector in Asia, including China and India. This makes sense, as the nitrogen fertilizer usage in these countries is the largest and the third-largest in the world and is only increasing."

Read the whole article in The Conversation.

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Peachtree to Paris: Emory delegation headed to U.N. climate talks

Reporting from Paris: Student updates on COP21

Among the 10 undergraduates representing Emory at COP21 are, from left: Savannah Miller, Naomi Maisel, Taylor McNair, Mae Bowen and Siyue Zong.

“In a basement auditorium in a quiet Parisian neighborhood, writer Naomi Klein held an event to talk about the ‘Leap Manifesto: A Call for a Canada Based on Caring for the Earth and One Another,’” reports Emory junior Clara Perez from the scene.

“Climate change, Klein said, is the catalyst to transformative change in all kinds of struggles – indigenous, class, anti-racism, among many others. She called for addressing climate change in a way that is ‘based on justice and redressing historical wrongs.’”

Now midway through a two-week trip to Paris, a delegation of Emory undergraduates are providing real-time updates on the 21st Session of the Conference of the Parties to the United Nations Framework Convention on Climate Change (COP21) and related events.

On the web site they’ve created, the students have posted photos of a demonstration that happened shortly after they landed in Paris. And they are gathering “snapshot” bios of other attendees, under the heading “Humans of COP21.”

Senior Taylor McNair writes: “From a business perspective, carbon pricing at COP21 is arguably the most exciting news to emerge from the first few days of the conference.”

Senior Mae Bowen was intrigued by an event at the Kedge Business School in Paris. Jean-Christophe Carteron presented a Sustainability Literacy Test he developed as a tool for universities and corporations to assess and develop the knowledge of their community members.

“While ‘sustainability’ is still a complicated term,” Bowen writes, “the goals of the Sustainability Literacy Test are admirable and a step in the right direction. No business or government leader should be able to claim ignorance when making decisions that negatively affect the future of our planet and humanity.”

Watch the web site for daily updates and follow the students’ updates on Twitter: @EmoryinParis.

And check out the podcasts that the students created as part of the Emory course “Paris is an Explanation: Understanding Climate Change at the 2015 United Nations Meeting in France.”

Related:
Peachtree to Paris: Emory delegation headed to U.N. climate talks

Nano-walkers take speedy leap forward with first rolling DNA-based motor

"Ours is the first rolling DNA motor, making it far faster and more robust," says Khalid Salaita, the Emory chemist who led the research. (Photos by Bryan Meltz, Emory Photo/Video.)

By Carol Clark

Physical chemists have devised a rolling DNA-based motor that’s 1,000 times faster than any other synthetic DNA motor, giving it potential for real-world applications, such as disease diagnostics. Nature Nanotechnology is publishing the finding.

“Unlike other synthetic DNA-based motors, which use legs to ‘walk’ like tiny robots, ours is the first rolling DNA motor, making it far faster and more robust,” says Khalid Salaita, the Emory University chemist who led the research. “It’s like the biological equivalent of the invention of the wheel for the field of DNA machines.”

The speed of the new DNA-based motor, which is powered by ribonuclease H, means a simple smart phone microscope can capture its motion through video. The researchers have filed an invention disclosure patent for the concept of using the particle motion of their rolling molecular motor as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water.

“Our method offers a way of doing low-cost, low-tech diagnostics in settings with limited resources,” Salaita says.

The field of synthetic DNA-based motors, also known as nano-walkers, is about 15 years old. Researchers are striving to duplicate the action of nature’s nano-walkers. Myosin, for example, are tiny biological mechanisms that “walk” on filaments to carry nutrients throughout the human body.

“It’s the ultimate in science fiction,” Salaita says of the quest to create tiny robots, or nano-bots, that could be programmed to do your bidding. “People have dreamed of sending in nano-bots to deliver drugs or to repair problems in the human body.”

So far, however, mankind’s efforts have fallen far short of nature’s myosin, which speeds effortlessly about its biological errands. “The ability of myosin to convert chemical energy into mechanical energy is astounding,” Salaita says. “They are the most efficient motors we know of today.”

Some synthetic nano-walkers move on two legs. They are essentially enzymes made of DNA, powered by the catalyst RNA. These nano-walkers tend to be extremely unstable, due to the high levels of Brownian motion at the nano-scale. Other versions with four, and even six, legs have proved more stable, but much slower. In fact, their pace is glacial: A four-legged DNA-based motor would need about 20 years to move one centimeter.



Kevin Yehl, a post-doctoral fellow in the Salaita lab, had the idea of constructing a DNA-based motor using a micron-sized glass sphere. Hundreds of DNA strands, or “legs,” are allowed to bind to the sphere. These DNA legs are placed on a glass slide coated with the reactant: RNA.

The DNA legs are drawn to the RNA, but as soon as they set foot on it they destroy it through the activity of an enzyme called RNase H. As the legs bind and then release from the substrate, they guide the sphere along, allowing more of the DNA legs to keep binding and pulling.

“It’s called a burnt-bridge mechanism,” Salaita explains. “Wherever the DNA legs step, they trample and destroy the reactant. They have to keep moving and step where they haven’t stepped in order to find more reactant.”

The combination of the rolling motion, and the speed of the RNase H enzyme on a substrate, gives the new DNA motor its stability and speed.

“Our DNA-based motor can travel one centimeter in seven days, instead of 20 years, making it 1,000 times faster than the older versions,” Salaita says. “In fact, nature’s myosin motors are only 10 times faster than ours, and it took them billions of years to evolve.”

Emory post-doctoral fellow Kevin Yehl sets up a smart-phone microscope to get a readout for the particle motion of the rolling DNA-based motor.

The researchers demonstrated that their rolling motors can be used to detect a single DNA mutation by measuring particle displacement. They simply glued lenses from two inexpensive laser pointers to the camera of a smart phone to turn the phone into a microscope and capture videos of the particle motion.

“Using a smart phone, we can get a readout for anything that’s interfering with the enzyme-substrate reaction, because that will change the speed of the particle,” Salaita says. “For instance, we can detect a single mutation in a DNA strand.”

This simple, low-tech method could come in handy for doing diagnostic sensing of biological samples in the field, or anywhere with limited resources.

The proof that the motors roll came by accident, Salaita adds. During their experiments, two of the glass spheres occasionally became stuck together, or dimerized. Instead of making a wandering trail, they left a pair of straight, parallel tracks across the substrate, like a lawn mower cutting grass. “It’s the first example of a synthetic molecular motor that goes in a straight line without a track or a magnetic field to guide it,” Salaita says.

In addition to Salaita and Yehl, the co-authors on the Nature Nanotechnology paper include Emory researchers Skanda Vivek, Yang Liu, Yun Zhang, Megzhen Fan, Eric Weeks and Andrew Mugler (who is now at Purdue University).

Related:
Chemists reveal the force within you
Molecular beacons shine light on how cells 'crawl'

Peachtree to Paris: Emory delegation headed to U.N. climate talks

On a recent Saturday, 30 students represented a country, or block of countries, to simulate the U.N. talks. Naomi Maisel, right, made the case for India. "You have to rethink your reality based on all the countries involved and figure out how to make it work," she says. (Beckysteinphotography.com)

By Carol Clark

More than 40,000 people from around the world are expected to descend on Paris, France, from November 30 to December 11, for what many see as the best chance yet for a universal climate agreement. The goal of the 21st Session of the Conference of the Parties to the United Nations Framework Convention on Climate Change (COP21) is to keep global warming to no more than 2 degrees Celsius since the start of the Industrial Revolution.

Everyone from President Obama to Atlanta Mayor Kasim Reed will be on the ground in Paris for high-stakes conversations about the fate of the planet. Ten Emory undergraduates and two faculty are also joining the historic event with the status of official U.N. observers.

“This is an unprecedented time,” says Taylor McNair, a senior majoring in environmental sciences and business. “People are coming into this conference with a mindset they have never had before. I’m optimistic that there will be some progress coming out of Paris, and that we will see some serious change during the next few years.”

McNair and three other Emory students will actually spend part of COP21 inside the main hall where delegates from 195 countries will negotiate reductions of their greenhouse gas emissions. And all 10 of the students will be gathering information from the milieu of related conferences, demonstrations, exhibits and informal discussions that will be humming around the main COP21 meeting.

The students will post photos and dispatches on a special web site they are creating for the event (http://climate.emorydomains.org), through the Emory Writing Program's Domain of One's Own. And they will use social media to further connect Emory and the Atlanta community to what’s happening in Paris, as it happens. You can follow their conversations on their Twitter handle @EmoryinParis, and via their hash tag: #PeachtreeToParis. Senior Tyler Stern is helping develop the team's social media platforms, which also include Instagram (EmoryParis15) and Snapchat (EmoryInParis).

After four hours of tense negotiations, students participating in simulated U.N. talks were only able to achieve caps on greenhouse gas emissions for a temperature rise of 3.5 degrees Celsius, short of the 2 degrees goal. 

“Climate change is not an issue that is coming in 100 years. It’s happening now,” says Naomi Maisel, a junior majoring in anthropology who will be making the trip. “We want to convey the sentiments of the people that we meet and give Emory students a sense of how the rest of the world is thinking about and dealing with climate change."

The students plan to also bring back lessons for what everyone can do to get involved. They will help organize an Emory “Climate Week” and a series of COP21 related events on campus in the Spring – including art exhibits, panel discussions and special lectures – in conjunction with the Climate@Emory initiative.

Debating the fate of the planet.

“I’m optimistic that some kind of meaningful deal will be reached in Paris,” says Mae Bowen, a senior majoring in environmental sciences and political science, who is headed for COP21. “But once a deal is made, that’s when the real work starts, making that deal come to fruition.”

The Paris trip is the capstone to a Coalition of the Liberal Arts (CoLA) course, aimed at integrating the liberal arts experience across the humanities and sciences. The course, “Paris is an Explanation: Understanding Climate Change at the 2015 United Nations Meeting in France,” was developed and taught by three faculty: Wesley Longhofer, an expert in organization and management at Goizueta Business School; Eri Saikawa, an expert in climate science in the department of environmental sciences and Rollins School of Public Health; and Sheila Tefft, senior lecturer in the Emory Writing Program. Bowen and another undergraduate, Adam Goldstein, also helped develop the course.

Both Longhofer and Saikawa will accompany the students on the trip to Paris.

Throughout the fall, the students are exploring climate change from environmental, business, media and political perspectives. Saikawa led discussions about the complex atmospheric science surrounding emissions. Longhofer organized mock UN negotiations so that the students could better understand perspectives of the various countries involved. Tefft focused on issues of communications and trained the students in journalistic techniques and technology, including podcasting and social media.

The Emory students have a range of research interests that they plan to hone in on as COP21 is underway. Below are brief bios, and a guide to their plans for Paris.

Taylor McNair

BUSINESS: Taylor McNair is a senior from West Port, Connecticut, majoring in business and environmental sciences. “I have a big interest in renewable energy,” he says. “I’ve had some work experience in that field and it’s helped shape what I think will be the defining challenge of the future: How will we switch from cheap fossil fuels and power our lives and economies with renewable energy?”

He notes that major companies like Google and Facebook have already announced they will be moving toward renewable energy sources for their datasets.

“We need more market-based solutions for addressing climate change,” he says. “It’s beginning to make economic sense to make investments in energy efficiency and renewable fuel sources. I think more people are waking up to the fact that this transition can not only be beneficial from an environmental and health aspect, but also from a financial aspect.”

POLICYMAKING: Mae Bowen is a senior majoring in environmental sciences and political science. Bowen, who is from Panama City, Florida, personally experienced the social and ecological impacts of hurricanes and the BP oil spill in the Gulf of Mexico. Even after the beaches near her home were cleaned and declared safe following the spill, tourists did not return for years due to public perceptions and media coverage.

Mae Bowen

“I was fascinated and frustrated by that,” Bowen says. “I’ve been thinking about the best ways to communicate environmental issues ever since.”

Bowen’s other passion is policymaking. She is a member of the Emory International Relations Association – a team of students that travels to universities across the country to participate in simulations of U.N. negotiations, based on real-world situations and research. While these exercises help Bowen see the challenges of policymaking, they have not made her cynical. “The fact that we have people from different countries and cultures coming together to try and solve a global problem like climate change – that’s kind of awesome,” she says. “I’m just so excited to go to COP21 and get to hear the actual deliberations over the issue I care most about.”

The Paris talks may not achieve the goal of reducing emissions to reach the goal of 2 degrees, “but it’s going to take us forward,” Bowen says. “I’m a big picture person. I would rather have a deal that goes part of the way than to have nothing at all. You have to take things one step at a time.”

Savannah Miller

EMORY AND ATLANTA: Savannah Miller, a senior majoring in environmental sciences and creative writing is focused on climate change adaptation and mitigation efforts at the local level. She is currently an intern for the city of Atlanta, working with the team developing a major climate action plan. “Emory was an early supporter of the Atlanta Better Buildings Challenge,” Miller says. “The university has been a leader in sustainability for years and our efforts keep gaining momentum.”

While at the Paris talks, she will be researching how other communities from around the world are implementing adaptive technologies and strategies for increasing energy efficiency. “One of our biggest goals is to bring back information about environmental policies and communicate them in a way that reaches our generation,” Miller says.

In addition to contributing to the Emory group web site for COP21, Miller has developed her own site, sustainable-directions.com, for communicating environmental issues. Her first post looked at the connections between climate change and recent historic flooding in her hometown of Charleston, South Carolina.

Naomi Maisel

AGRICULTURE: Naomi Maisel, a junior majoring in anthropology, is researching the impact of climate change on agriculture and food security. “Farmers are starting to see effects faster and more intensely, especially in the developing world,” Maiesel says. “We don’t know if a lot of food systems can withstand more or less rainfall, more or less heat, and higher concentrations of carbon dioxide.”

Maisel contacted a farmer outside of Paris who has agreed to give the students a tour of his farm and explain his experience of climate change.

While growing up in San Diego, Maisel recalls that many discussions about climate change were debates about whether it was happening. “Now, most of the conversations I’m hearing revolve around questions like, how bad is it going to be and what are we doing about it,” she says. “People are finally starting to take it seriously. And they realize that it is not just a science problem. It’s an economic issue, a security issue and a public health issue. Everybody is going to be affected, so everybody needs to be involved.”

Clara Perez, a junior majoring in sociology and sustainability, is focused on how climate change will disproportionately impact lower socio-economic groups.

Caiwei Huang (a junior majoring in interdisciplinary studies and political science) and Siyue Zong (a senior environmental sciences major) both want to follow the crucial negotiations of the two biggest greenhouse gas emitters: The United States and China. (Huang is developing a web site to introduce students to the fundamentals of Chinese politics: thecapitalc.org.)

Samuel Budnyk, a junior majoring in comparative literature and music, is especially interested in communicating to the general public and hopes to write a post a day for the Emory Wheel during the talks.

Adam Goldstein and Mark Leone (both seniors majoring in business) will be focused on gathering information about climate finance – the move toward investing in low-carbon and more resilient economies.

How close are we to living on Mars?

Matt Damon portrays an astronaut stranded on Mars in "The Martian." The movie opens this week, on the heels of NASA's discovery of liquid water on the Red Planet.

By Sidney Perkowitz, Emeritus Candler Professor of Physics at Emory

Like any long-distance relationship, our love affair with Mars has had its ups and downs. The planet’s red tint made it a distinctive – but ominous – nighttime presence to the ancients, who gazed at it with the naked eye. Later we got closer views through telescopes, but the planet still remained a mystery, ripe for speculation.

A century ago, the American astronomer Percival Lowell mistakenly interpreted Martian surface features as canals that intelligent beings had built to distribute water across a dry world. This was just one example in a long history of imagining life on Mars, from H G Wells portraying Martians as bloodthirsty invaders of Earth, to Edgar Rice Burroughs, Kim Stanley Robinson and others wondering how we could visit Mars and meet the Martians.

Drawing of Mars via NASA

The latest entry in this long tradition is the sci-fi flick The Martian, to be released on October 2. Directed by Ridley Scott and based on Andy Weir’s self-published novel, it tells the story of an astronaut (played by Matt Damon) stranded on Mars. Both book and movie try to be as true to the science as possible – and, in fact, the science and the fiction around missions to Mars are rapidly converging.

NASA’s Curiosity rover and other instruments have shown that Mars once had oceans of liquid water, a tantalizing hint that life was once present.

And now NASA has just reported the electrifying news that liquid water is flowing on Mars.

This discovery increases the odds that there is currently life on Mars – picture microbes, not little green men – while heightening interest in NASA’s proposal to send astronauts there by the 2030s as the next great exploration of space and alien life.

So how close are we to actually sending people to Mars and having them survive on an inhospitable planet? First we have to get there.

Making it to Mars won’t be easy. It’s the next planet out from the sun, but a daunting 140 million miles away from us, on average – far beyond the Earth’s moon, which, at nearly 250,000 miles away, is the only other celestial body human beings have set foot on.

Nevertheless, NASA and several private ventures believe that by further developing existing propulsion methods, they can send a manned spacecraft to Mars.
 


One NASA scenario would, over several years, pre-position supplies on the Martian moon Phobos, shipped there by unmanned spacecraft; land four astronauts on Phobos after an eight-month trip from Earth; and ferry them and their supplies down to Mars for a 10-month stay, before returning the astronauts to Earth.

We know less, though, about how a long voyage inside a cramped metal box would affect crew health and morale. Extended time in space under essentially zero gravity has adverse effects, including loss of bone density and muscle strength, which astronauts experienced after months aboard the International Space Station (ISS).

There are psychological factors, too. ISS astronauts in Earth orbit can see and communicate with their home planet, and could reach it in an escape craft, if necessary. For the isolated Mars team, home would be a distant dot in the sky; contact would be made difficult by the long time lag for radio signals. Even at the closest approach of Mars to the Earth, 36 million miles, nearly seven minutes would go by before anything said over a radio link could receive a response.

To cope with all this, the crew would have to be carefully screened and trained. NASA is now simulating the psychological and physiological effects of such a journey in an experiment that is isolating six people for a year within a small structure in Hawaii.

Engineers and technicians are already testing the spacesuit astronauts will wear in the Orion spacecraft on trips to deep space, including Mars. (NASA/Bill Stafford)

These concerns would continue during the astronauts' stay on Mars, which is a harsh world. With temperatures that average -80 Fahrenheit (-62 Celsius) and can drop to -100F (-73C) at night, it is cold beyond anything we encounter on Earth; its thin atmosphere, mostly carbon dioxide (CO₂), is unbreathable and supports huge dust storms; it is subject to ultraviolet radiation from the sun that may be harmful; and its size and mass give it a gravitational pull that is only 38% of the Earth’s – which astronauts exploring the surface in heavy protective suits would welcome, but could also further exacerbate bone and muscle problems.

As the astronauts establish their base, NASA is planning to use Mars' own resources to overcome some of these obstacles.

Fortunately, water and oxygen should be available. NASA had planned to try a form of mining to retrieve water existing just below the Martian surface, but the new finding of surface water may provide an easier solution for the astronauts. Mars also has considerable oxygen bound up in its atmospheric CO₂. In the MOXIE process (Mars Oxygen In situ resource utilization Experiment), electricity breaks up CO₂ molecules into carbon monoxide and breathable oxygen. NASA proposes to test this oxygen factory aboard a new Mars rover in 2020 and then scale it up for the manned mission.

There is also potential to produce the compound methane from Martian sources as rocket fuel for the return to Earth. The astronauts should be able to grow food, too, using techniques that recently allowed the ISS astronauts to taste the first lettuce grown in space.

Without utilizing some of Mars' raw materials, NASA would have to ship every scrap of what the astronauts would need: equipment, their habitation, food, water, oxygen and rocket fuel for the return trip. Every extra pound that has to be hauled up from Earth makes the project that much more difficult. “Living off the land” on Mars, though it might affect the local environment, would hugely improve the odds for success of the initial mission – and for eventual settlements there.

NASA will continue to learn about Mars and hone its planning over the next 15 years. Of course, there are formidable difficulties ahead; but it’s key that the effort does not require any major scientific breakthroughs, which, by their nature, are unpredictable. Instead, all the necessary elements depend on known science being applied via enhanced technology.

Yes, we’re closer to Mars than many may think. And a successful manned mission could be the signature human achievement of our century.

(This article first appeared in The Conversation.)

Chemistry Center ignites celebration of science

“Why do I have a garbage can full of liquid nitrogen? Because I’m a chemist,” Doug Mulford, director of undergraduate education for Emory’s Department of Chemistry, told a crowd of enthralled children and adults.

Decked out in safety glasses and a red lab coat printed with flames, Mulford conducted a ribbon immolation ceremony on Saturday, to officially open Emory’s Sanford S. Atwood Chemistry Center addition. The crowd gasped and cheered in the courtyard as Mulford ignited a thermite reaction, a pyrotechnic mixture of aluminum and iron oxide. The reaction shot off sparks and smoking-hot globules of molten iron to sever the ceremonial ribbon.

Rain did not dampen anyone’s enthusiasm for the grand opening, which included fun science demonstrations by students from chemistry, biology and physics.

In fact, chemists love water droplets and clouds. Graduate students from Emory’s Pi Alpha Chemical Society showed how to make both, using liquid nitrogen.

“We’re pouring really hot water into really cold liquid nitrogen, causing it to expand into a plume of air that comes up as a cloud,” explained Daniel Collins-Wildman, who braved nature’s drizzle in the courtyard along with fellow graduate student Amanda Dermer.

In fact, Collins-Wildman said, the liquid nitrogen is so cold (77 Kelvin) that ice particles form in the cloud, creating what is known as a nucleation site where water drops can form.

“I conducted an experiment with this by accident once, when I was making macaroni and cheese,” he said. He brought the water to a roiling boil. As usual, bubbles formed along the sides of the pot, where the temperature is higher and the pot’s irregular surface creates the potential for nucleation. Then the power went out. The bubbles on the sides of the pot disappeared. The water was still hot when he turned the heat back on. Without the small bubbles acting as nucleation sites the water boiled violently, a phenomenon known in chemistry as "bumping."

"I heard this weird sound," Collins-Wildman said. "All those little bubbles that had formed slowly before, this time formed immediately as one huge bubble that came to the surface with a BLURP!”

Related:
Chemistry Center turns up the heat for grand opening

Leaping molecules! How a frog evolved violet vision

The story of the evolution of color vision in the African clawed frog, above, "is full of mysterious twists and turns," says evolutionary biologist Shozo Yokoyama. Photo by Brian Gratwicke.

By Carol Clark

The African clawed frog is tongue-less, has long, curvy toes and eyes that are perched on top of its head, but that’s not all that’s odd about it. This species of frog also took a strange evolutionary path to change from ultraviolet to violet vision: Some of its visual pigment molecules kept trying to leap ahead, but other molecules shut them down and kept the process moving at a crawl. 

Science Advances published the complete molecular interactions involved in the pathway, as detailed in a study led by Shozo Yokoyama, a biologist at Emory University who specializes in adaptive evolution of vision.

“It’s the most bizarre, and sophisticated, case of color vision evolution that I’ve ever encountered,” says Yokoyama, who previously headed up efforts to construct the most extensive evolutionary tree for vision, including 500 species of animals, from eels to humans.

“This frog had these quirks for rapid molecular change, but it also had something to control these quirks,” he says. “In fact, it had triple protection.”

Five classes of opsin genes encode visual pigments for dim-light and color vision. Bits and pieces of the opsin genes change and vision adapts as the environment of a species changes.

Ultraviolet (UV) vision gives a bi-chromatic, high-contrast view of the world that can be useful for many basic behaviors. Mice, for instance, are mainly nocturnal and mark their territory with urine and feces that reflects UV light for other mice. Unfortunately for mice, however, many of their predators are also UV sensitive so they, too, can spot these signs of mice more easily.

Violet vision, or the ability to see blue light, provides better resolution and detail for colors in a scene. Among the possible reasons that frogs evolved from UV to violet sensitivity may have been to give them a better view of potential mates. It may also have improved their ability to pick out predators – such as a green snake amid green leaves.

In other recent research, Shozo Yokoyama, above, finished the first detailed and complete picture of the evolution of human vision. Photo by Bryan Meltz, Emory Photo/Video.

In previous research on the African clawed frog (Xenopus laevis), Yokoyama and collaborators had identified some of the genetic mutations involved in the process of the frog’s switch from UV vision to its current function of violet vision. They also noticed that amino acid site 113 on this pigment of the African clawed frog had changed from glutamic acid to aspartic acid.

“Out of all the species in the animal kingdom that have been studied, site 113 is made up of glutamic acid, but this frog had changed site 113 to aspartic acid,” Yokoyama says. “Why did it do that? This question was very mysterious and interesting to me. What is so special about this frog?”

Yokoyama studies ancestral molecules to tease out secrets of adaptive evolution. The lengthy process involves teams of collaborators to first estimate and synthesize ancestral proteins and pigments of a species, then conduct experiments on them. The technique combines microbiology with theoretical computation, biophysics, quantum chemistry and genetic engineering.

For the current paper, he and his co-authors found that 12 mutations were involved in the frog’s vision shift. These 12 molecular changes could have 500 million possible combinations of pathways that connect the ancestral UV vision and the frog’s violet vision. The researchers narrowed the problem down and focused on changes in the six layers of transmembranes where the 12 molecules in the process are located. That focus reduced the number of possible evolutionary pathways to 720.

They then assembled molecular “chimeras” between the ancestral and frog pigments for all of these pathways. They tested how the molecules functioned in all the different combinations, to hone in on the right pathway.

The results showed that the mutations that occurred on transmembranes four, five and six happened early during the evolutionary process. It was not until eons later, however, that these mutations came into play.

The mutations occurring on transmembrane two caused small shifts in the range of the light spectrum that the pigment detected. The mutations occurring early in evolution on transmembrane three, however, where site 113 resides, caused a big jump in the light-wave range – from 400 nanometers to 600 nanometers. 

“Rapid change is not convenient evolutionarily,” Yokoyama says. “In fact, it can be a disaster.” 

He uses the example of emerging from a darkened movie theater on a sunny day, and being temporarily blinded until your eyes adjust to the new environment.

Three times, molecules on transmembrane three mutated to cause a big jump toward violet sensitivity. The first time it happened, transmembrane five came into play, shrinking the molecular structure of the pigment and making it non-functional.

The second time that transmembrane three mutated, launching another jump, transmembrane six sprang into action, again shrinking the molecular structure.

The third time transmembrane three tried to make the evolutionary leap, number four shut it down by destroying a critical chemical structure of the pigment.

The frog pigment essentially put on the brakes early during the evolutionary process for the mutations from glutamic acid to aspartic acid at site 113. Only towards the end of the process did the pigment accept the site 113 shifts. By then, Yokoyama explains, the changes to the frog’s light spectrum were no longer a big jump. Instead, they were just 15 nanometers.

“The human process for evolving from UV to violet vision was far more simple and straight-forward,” Yokoyama says. “The story of this frog is full of mysterious twists and turns. A series of strange coincidences happened at the right time, at the right spot, for the right species.”

Yokoyama’s co-authors for the current paper include Emory biologists Huiyong Jia, Takashi Koyama, Davide Faggionato and Yang Liu; and Ahmet Altun of Faith University in Istanbul and William Starmer of Syracuse University.

Related:
A clear, molecular view of the evolution of human color vision

Why women rule, and other hot science topics at the Decatur Book Festival

Illustration: Don Morris

Women can forget about equality with men, warns Emory anthropologist Mel Konner.

It’s even better than that. Why should women embrace mere equality when their movement is toward superiority? It is maleness that has Konner worried in his latest book, “Women After All: Sex, Evolution and the End of Male Supremacy,” which looks at the history and future of gender and power dynamics.

Konner will be one of the featured authors in the ever-popular Science track of the Decatur Book Festival this weekend. He’ll take the stage at 3 pm on Saturday, September 5, at the Marriot Conference Center.

The last line of Konner’s book jacket reads: “Provocative and richly informed, ‘Women After All’ is bound to be controversial across the sexes.”

As Konner acknowledges on his personal web site, the first murmurings came about after a short adaptation of the book ran in the Wall Street Journal. Hundreds of angry men responded within a couple of days. His wife, home alone during that period, double-locked the door. Konner’s editor at the Wall Street Journal apologized for failing to instruct him not to read the comments.

For his part, Konner is hiding in plain sight, saying “Clearly, I’ve touched a nerve, and I’m happy about that.”

Konner talks about a future that his grandson will inhabit, a “new world” that “will be better for him because women help run it.”

You can read more about Konner’s book in the latest issue of Emory Magazine.

Another provocative issue at the intersection of science and society is explored in “Vaccine Nation: America’s Changing Relationships with Immunization,” by Emory historian Elena Conis. She will discuss her book at 4:15 pm on Saturday at the Marriott Conference Center.

Biophysicists take small step in quest for 'robot scientist'

The researchers dubbed their algorithm "Sir Isaac," in a nod to one of the greatest scientists of all time, Sir Isaac Newton. 

By Carol Clark

Biophysicists have taken another small step forward in the quest for an automated method to infer models describing a system’s dynamics – a so-called robot scientist. Nature Communications published the finding – a practical algorithm for inferring laws of nature from time-series data of dynamical systems.

“Our algorithm is a small step,” says Ilya Nemenman, lead author of the study and a professor of physics and biology at Emory University. “It could be described as a toy version of a robot scientist, but even so it may have practical applications. For the first time, we’ve taught a computer how to efficiently search for the laws that underlie arbitrary, natural dynamical systems, including complex, non-linear biological systems.”

Nemenman’s co-author on the paper is Bryan Daniels, a biophysicist at the University of Wisconsin.

Everything that is changing around us and within us – from the relatively simple motion of celestial bodies, to weather and complex biological processes – is a dynamical system. A large part of science is guessing the laws of nature that underlie such systems, summarizing them in mathematical equations that can be used to make predictions, and then testing those equations and predictions through experiments.

“The long-term dream is to harness large-scale computing to make the guesses for us and speed up the process of discovery,” Nemenman says.

Isaac Newton contemplates gravity beneath an apple tree. The intuition of a genius like Newton is one quality that distinguishes human intelligence from even the highest-powered computer and algorithmic program.

While the quest for a true robot scientist, or computerized general intelligence, remains elusive, this latest algorithm represents a new approach to the problem. “We think we have beaten any automated-inference algorithm that currently exists because we focus on getting an approximate solution to a problem, which we can get with much less data,” Nemenman says.

In previous research, John Wikswo, a biophysicist at Vanderbilt University, along with colleagues at Cornell University, applied a software system to automate the scientific process for biological systems.

“We came up with a way to derive a model of cell behavior, but the approach is complicated and slow, and it is limited in the number of variables that it can track – it can’t be scaled to more complicated systems,” Wikswo says. “This new algorithm increases the speed of the necessary calculation by a factor of 100 or more. It provides an elegant method to generate compact and effective models that should allow prediction and control of complex systems.”

Nemenman and Daniels dubbed their new algorithm “Sir Issac.”

The real Sir Isaac Newton serves as a classic example of how the scientific method involves forming hypotheses, then testing them by looking at data and experiments. Newton guessed that the same rules of gravity applied to a falling apple and to the moon in orbit. He used data to test and refine his guess and generated the law of universal gravitation.

To test their algorithm, Nemenman and Daniels created an artificial, model solar system by generating numerical trajectories of planets and comets that move around a sun. In this simplified solar system, only the sun attracted the planets and comets.

Images of the moon by NASA's Galileo spacecraft. Everything that is changing around us and within us – from the relatively simple motion of celestial bodies, to weather and complex biological processes – is a dynamical system.

“We trained our algorithm how to search through a group of laws which were limited enough to be practical, but also flexible enough to explain many different dynamics,” Nemenman explains. “We then gave the algorithm some simulated planetary trajectories, and asked it what makes these planets move. It gave us the universal gravitational force. Not perfectly, but with very good accuracy. The error was just a few percent.”

The algorithm also figured out that force changes velocity, not the position directly. “It gets Newton’s First Law,” Nemenman says, “the fact that in order to predict the possible trajectory of a planet, whether it stays near the sun or flies off into infinity, just knowing its initial position is not enough. The algorithm understands that you also need to know the velocity.”

While most modern-day high school student know Newton’s First Law, it took humanity 2,000 years beyond the time of Aristotle to discover it.

One limitation of the algorithm is inexactness. Getting an approximate model, however, is beneficial as long as the approximation is close enough to make good predictions, Nemenman says.

“Newton’s laws are also approximate, but they have been remarkably beneficial for 350 years,” he says. “We’re still using them to control everything from electron microscopes to rockets.”

Getting an exact description of any complex dynamical system requires large amounts of data, he adds. “In contrast, with our algorithm, we can get an approximate description by using just a few measurements of a system. That makes our method practical.”

The researchers demonstrated, for example, that the algorithm can infer the dynamics of a caricature of an immune receptor in a leukocyte. This type of model could lead to a better understanding of the time-course for the response to an infection or a drug.

In another experiment, the researchers fed the algorithm data on concentrations of just three different species of chemicals involved in glycolysis in yeast. The algorithm generated a model that makes accurate predictions for the full system of this basic metabolic process to consume glucose, which involves seven chemical species.

“If you applied other methods of automatic inference to this system it would typically take tens of thousands of examples to reliably generate the laws that drive these chemical transformations,” Nemenman says. “With our algorithm, we were able to do it with fewer than 100 examples.”

With their experimental collaborators, the researchers are now exploring whether the algorithm can model more complex biological processes, such as the dynamics of insulin secretion in the pancreas and its relationship to the onset of a disease like diabetes. “The biology of insulin secreting cells is extremely complex. Understanding their dynamics on multiple scales is going to be difficult, and may not be possible for years with traditional methods,” Nemenman says. “But we want to see if we can get a good enough approximation with our method to deliver a practical result.”

The intuition of a genius mind like that of Isaac Newton is one quality that distinguishes human intelligence from even the highest-powered computer and algorithmic program.

“You can’t give a machine intuition – at least for now,” Nemenman says. “What we’re hoping we can do is get our computer algorithm to spit out models of phenomena so that we, as scientists, can use them and our intuition to make useful generalizations. It’s easier to generalize from models of specific systems then it is to generalize from various data sets directly.”

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Biology may not be so complex after all