How protein misfolding may kickstart chemical evolution

The origami of disease, and of life: Research into the abnormal folding of proteins related to neurodegenerative conditions is providing insights into how life may emerge from a chemical system.

By Carol Clark

Alzheimer’s disease, and other neurodegenerative conditions involving abnormal folding of proteins, may help explain the emergence of life – and how to create it.

Researchers at Emory University and Georgia Tech demonstrated this connection in two new papers published by Nature Chemistry: “Design of multi-phase dynamic chemical networks” and “Catalytic diversity in self-propagating peptide assemblies.”

“In the first paper we showed that you can create tension between a chemical and physical system to give rise to more complex systems. And in the second paper, we showed that these complex systems can have remarkable and unexpected functions,” says David Lynn, a systems chemist in Emory’s Department of Chemistry who led the research. “The work was inspired by our current understanding of Darwinian selection of protein misfolding in neurodegenerative diseases.”

The Lynn lab is exploring ways to potentially control and direct the processes of these proteins – known as prions – adding to knowledge that might one day help to prevent disease, as well as open new realms of synthetic biology. For the current papers, Emory collaborated with the research group of Martha Grover, a professor in the Georgia Tech School of Chemical & Biomolecular Engineering, to develop molecular models for the processes.

“Modeling requires us to formulate our hypotheses in the language of mathematics, and then we use the models to design further experiments to test the hypotheses,” Grover says.

Darwin’s theory of evolution by natural selection is well-established – organisms adapt over time in response to environmental changes. But theories about how life emerges – the movement through a pre-Darwinian world to the Darwinian threshold – remain murkier.

The researchers started with single peptides and engineered in the capacity to spontaneously form small proteins, or short polymers. “These protein polymers can fold into a seemingly endless array of forms, and sometimes behave like origami,” Lynn explains. “They can stack into assemblies that carry new functions, like prions that move from cell-to-cell, causing disease.”

This protein misfolding provided the model for how physical changes could carry information with function, a critical component for evolution. To try to kickstart that evolution, the researchers engineered a chemical system of peptides and coupled it to the physical system of protein misfolding. The combination results in a system that generates step-by-step, progressive changes, through self-driven environmental changes.

“The folding events, or phase changes, drive the chemistry and the chemistry drives the replication of the protein molecules,” Lynn says. “The simple system we designed requires only the initial intervention from us to achieve progressive growth in molecular order. The challenge now becomes the discovery of positive feedback mechanisms that allow the system to continue to grow.”

The research was funded by the McDonnell Foundation, the National Science Foundation’s Materials Science Directorate, Emory University’s Alzheimer’s Disease Research Center, the National Science Foundation’s Center for Chemical Evolution and the Office of Basic Energy Sciences of the U.S. Department of Energy.

Additional co-authors of the papers include: Toluople Omosun, Seth Childers, Dibyendu Das and Anil Mehta (Emory Departments of Chemistry and Biology); Ming-Chien Hsieh (Georgia Tech School of Chemical and Biomolecular Engineering); and Neil Anthony and Keith Berland (Emory Department of Physics).

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Contact tracing, with indoor spraying, can curb dengue outbreak

A traditional Queenslander home in Cairns, Australia, is open to breezes, as well as to disease-bearing mosquitoes. (Photo via James Cook University.)

By Carol Clark

Contact tracing, combined with targeted, indoor residual spraying of insecticide, can greatly reduce the spread of the mosquito-borne dengue virus, finds a study led by Emory University.

In fact, this novel approach for the surveillance and control of dengue fever – spread by the same mosquito species that infects people with the Zika virus – was between 86 and 96 percent effective during one outbreak, the research shows. By comparison, vaccines for the dengue virus are only 30-to-70-percent effective, depending on the serotype of the virus.

Science Advances published the findings, which were based on analyses from a 2009 outbreak of dengue in Cairns, Australia.

“We’ve provided evidence for a method that is highly effective at preventing transmission of diseases carried by the Aedes aegypti mosquito in a developed, urban setting,” says the study’s lead author, Gonzalo Vazquez-Prokopec, a disease ecologist in Emory’s Department of Environmental Sciences. “We’ve also shown the importance of human movement when conducting surveillance of these diseases.”

“The United States is facing continual threats from dengue, chikungunya and Zika viruses,” says Sam Scheiner, director of the National Science Foundation’s Ecology and Evolution of Infectious Diseases Program, which funded the research. “For now, the response is to intensively spray insecticides. This research shows that a more targeted approach can be more effective.”

While the method would likely not be applicable everywhere, Vazquez-Prokopec says that it may be viable to control Aedes-borne diseases in places with established health systems and similar environmental characteristics to Cairns, such as South Florida or other U.S. states at risk of virus introduction.

“The widespread transmission of dengue viruses, coupled with the birth defects associated with Zika virus, shows the dire need for as many weapons as possible in our arsenal to fight diseases spread by these mosquitos,” he says. “Interventions need to be context dependent and evaluated carefully and periodically.”

A public health worker collects Aedes mosquito larvae from water that has pooled on a tarp at a residence in Cairns, Australia.

During the dengue outbreak in Cairns, public health officials traced recent contacts of people with a confirmed infection – a surveillance method known as contact tracing. This method is commonly used for directly transmitted pathogens like Ebola or HIV, but rarely for outbreaks spread by mosquitos or other vectors.

Using mobility data from the known cases, public health workers targeted residences for indoor residual spraying, or IRS. Walls of the homes – from top to bottom – and dark, humid places where Aedes mosquitos might rest, were sprayed with an insecticide that lasts for months.

The method is time-consuming and labor intensive, and health officials were not able to reach all of the residences that were connected to the infected persons.

The researchers found that performing IRS in potential exposure locations reduced the probability of dengue transmission by at least 86 percent in those areas, in comparison to areas of potential exposures that did not have indoor spraying.

“The findings are important,” Vazquez-Prokopec says, “because they demonstrate one of the few measures that we have for the effectiveness of an intervention to reduce the transmission of dengue.”

Many times, he says, in the face of a dengue outbreak public health officials end up using trucks to spray insecticide – despite the lack of scientific evidence for the effectiveness of fogging from the streets to control Aedes aegypti mosquitos.

Quantifying the effectiveness of existing methods, and the context within which they work, can strengthen the vector-control arsenal. “We need to develop plans for outbreak containment that are context-specific,” Vazquez-Prokopec says.

He is researching ways to scale up this intervention. While it now takes approximately half-an-hour to conduct indoor residual spraying in a single house, he would like to cut that time to as little as 10 minutes.

“We are evaluating how we can scale up and improve IRS for 21st-century urban areas,” Vazquez-Prokopec says.

Co-authors of the study include researchers from Queensland Health, the Rollins School of Public Health and James Cook University, Cairns.

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How dads bond with toddlers: Brain scans link oxytocin to paternal nurturing

The findings show that "fathers, and not just mothers, undergo hormonal changes that are likely to facilitate increased empathy and motvation to care for their children," says Emory anthropologist James Rilling.

By Carol Clark

Fathers given boosts of the hormone oxytocin show increased activity in brain regions associated with reward and empathy when viewing photos of their toddlers, an Emory University study finds. 

“Our findings add to the evidence that fathers, and not just mothers, undergo hormonal changes that are likely to facilitate increased empathy and motivation to care for their children,” says lead author James Rilling, an Emory anthropologist and director of the Laboratory for Darwinian Neuroscience. “They also suggest that oxytocin, known to play a role in social bonding, might someday be used to normalize deficits in paternal motivation, such as in men suffering from post-partum depression.”

The journal Hormones and Behavior published the results of the study, the first to look at the influence of both oxytocin and vasopressin – another hormone linked to social bonding – on brain function in human fathers.

A growing body of literature shows that paternal involvement plays a role in reducing child mortality and morbidity, and improving social, psychological and educational outcomes. But not every father takes a “hands-on” approach to caring for his children.

“I’m interested in understanding why some fathers are more involved in caregiving than others,” Rilling says. “In order to fully understand variation in caregiving behavior, we need a clear picture of the neurobiology and neural mechanisms that support the behavior.”

Researchers have long known that when women go through pregnancy they experience dramatic hormonal changes that prepare them for child rearing. Oxytocin, in particular, was traditionally considered a maternal hormone since it is released into the bloodstream during labor and nursing and facilitates the processes of birth, bonding with the baby and milk production.

More recently, however, it became clear that men can also undergo hormonal changes when they become fathers, including increases in oxytocin. Evidence shows that, in fathers, oxytocin facilitates physical stimulation of infants during play as well as the ability to synchronize their emotions with their children.

In order to investigate the neural mechanisms involved in oxytocin and paternal behavior, the Rilling lab used functional Magnetic Resonance Imaging (fMRI) to compare neural activity in men with and without doses of oxytocin, administered through a nasal spray. The participants in the experiment were all healthy fathers of toddlers, between the ages of one and two. While undergoing fMRI brain scans, each participant was shown a photo of his child, a photo of a child he did not know and a photo of an adult he did not know.

When viewing an image of their offspring, participants dosed with oxytocin showed significantly increased neural activity in brain systems associated with reward and empathy, compared to placebo. This heightened activity (in the caudate nucleus, dorsal anterior cingulate and visual cortex) suggests that doses of oxytocin may augment feelings of reward and empathy in fathers, as well as their motivation to pay attention to their children.

Surprisingly, the study results did not show a significant effect of vasopressin on the neural activity of fathers, contrary to the findings of some previous studies on animals.

Research in prairie voles, which bond for life, for instance, has shown that vasopressin promotes both pair-bonding and paternal caregiving. “It could be that evolution has arrived at different strategies for motiving paternal caregiving in different species,” Rilling says.

Co-authors of the study include Ting Li (Emory Anthropology), Xu Chen (Emory Anthropology and the School of Medicine’s Department of Psychiatry and Behavioral Sciences), Jennifer Mascaro (Emory School of Medicine Department of Family and Preventive Medicine) and Ebrahim Haroon (Department of Psychiatry and Behavioral Sciences)

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Brazilian peppertree packs power to knock out antibiotic-resistant bacteria

The weed whisperer: Ethnobotanist Cassandra Quave uncovered a medicinal mechanism in berries of the Brazilian peppertree. The plant is a weedy invasive species in Florida, but valued by traditional healers in the Amazon as a treatment for infections. (Photos by Ann Bordon, Emory Photo/Video)

By Carol Clark

The red berries of the Brazilian peppertree – a weedy, invasive species common in Florida – contain an extract with the power to disarm dangerous antibiotic-resistant staph bacteria, scientists at Emory University have discovered.

The journal Scientific Reports published the finding, made in the lab of Cassandra Quave, an assistant professor in Emory’s Center for the Study of Human Health and in the School of Medicine’s Department of Dermatology.

“Traditional healers in the Amazon have used the Brazilian peppertree for hundreds of years to treat infections of the skin and soft tissues,” Quave says. “We pulled apart the chemical ingredients of the berries and systematically tested them against disease-causing bacteria to uncover a medicinal mechanism of this plant.”

Brazilian peppertree, Schinus terebinthifolia

The researchers showed that a refined, flavone-rich composition extracted from the berries inhibits formation of skin lesions in mice infected with methicillin-resistant Staphylococcus auereus (MRSA). The compound works not by killing the MRSA bacteria, but by repressing a gene that allows the bacteria cells to communicate with one another. Blocking that communication prevents the cells from taking collective action, a mechanism known as quorum quenching.

“It essentially disarms the MRSA bacteria, preventing it from excreting the toxins it uses as weapons to damage tissues,” Quave says. “The body’s normal immune system then stands a better chance of healing a wound.”

The discovery may hold potential for new ways to treat and prevent antibiotic-resistant infections, a growing international problem. Antibiotic-resistant infections annually cause at least two million illnesses and 23,000 deaths in the United States, according to the Centers for Disease Control and Prevention. The United Nations last year called antibiotic-resistant infections a “fundamental threat” to global health and safety, citing estimates that they cause at least 700,000 deaths each year worldwide, with the potential to grow to 10 million deaths annually by 2050.

Blasting deadly bacteria with drugs designed to kill them is helping to fuel the problem of antibiotic resistance. Some of the stronger bacteria may survive these drug onslaughts and proliferate, passing on their genes to offspring and leading to the evolution of deadly “super bugs.”

In contrast, the Brazilian peppertree extract works by simply disrupting the signaling of MRSA bacteria without killing it. The researchers also found that the extract does not harm the skin tissues of mice, or the normal, healthy bacteria found on skin.

“In some cases, you need to go in heavily with antibiotics to treat a patient,” Quave says. “But instead of always setting a bomb off to kill an infection, there are situations where using an anti-virulence method may be just as effective, while also helping to restore balance to the health of a patient. More research is needed to better understand how we can best leverage anti-virulence therapeutics to improve patient outcomes.”

Quave, a leader in the field of medical ethnobotany and a member of the Emory Antibiotic Resistance Center, studies how indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs.

Cassandra Quave with her lab manager James Lyles, a co-author of the Brazilian peppertree study and a post-doctoral fellow at Emory.

The Brazilian peppertree (Schinus terebinthifolia) is native to South America but thrives in subtropical climates. It is abundant in much of Florida, and has also crept into southern areas of Alabama, Georgia, Texas and California. Sometimes called the Florida holly or broad leaf peppertree, the woody plant forms dense thickets that crowd out native species.

“The Brazilian peppertree is not some exotic and rare plant found only on a remote mountaintop somewhere,” Quave says. “It’s a weed, and the bane of many a landowner in Florida.”

From an ecological standpoint, it makes sense that weeds would have interesting chemistry, Quave adds. “Persistent, weedy plants tend to have a chemical advantage in their ecosystems, which may help protect them from diseases so they can more easily spread in a new environment.”

The study's co-authors include Amelia Muhs and James Lyles (Emory Center for the Study of Human Health); Kate Nelson (Emory School of Medicine); and Corey Parlet, Jeffery Kavanaugh and Alexander Horswill (University of Iowa). The laboratory experiments were conducted in collaboration between the Quave and Horswill labs with funding from the National Center for Complementary and Integrative Health, National Institutes of Health.

The Quave lab is now doing additional research to confirm the safest and most effective means of using the Brazilian peppertree extract. The next step would be pre-clinical trials to test its medicinal benefits. “If the pre-clinical trials are successful, we will apply for an application to pursue clinical trials, under the Food and Drug Administration’s botanical drug pathway,” Quave says.

The Brazilian peppertree finding follows another discovery made by the Quave lab in 2015: The leaves of the European chestnut tree also contain ingredients with the power to disarm staph bacteria without increasing its drug resistance.

While both the Brazilian peppertree and chestnut tree extracts disrupted the signaling needed for quorum quenching, the two extracts are made up of different chemical compounds.

“The latest classes of antibiotics introduced to the market were actually discovered between the 1950s and 1980s,” Quave says. “Scientists have just been building off the same building blocks of earlier classes and modifying them slightly to create new antibiotics. Examining the extracts of plants used by traditional healers for infections may open up discovery of new chemical scaffolds for drug design, and provide important pathways for battling antibiotic-resistance.”

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Tapping traditional remedies to fight modern super bugs
A future without antibiotics?

Astronaut Mark Kelly to launch Atlanta Science Festival at Emory

Captain Mark Kelly, who led NASA missions into space, will lead off the action-packed schedule of this year's Atlanta Science Festival on Tuesday, March 14. His talk is entitled "Endeavor to Succeed." (NASA photo)

By Carol Clark

The 2017 Atlanta Science Festival blasts off on Tuesday, March 14 with a talk by Captain Mark Kelly – commander of Space Shuttle Endeavour’s final mission – at 7 pm in Emory’s Glenn Memorial Auditorium.

“We wanted to start off this year with someone who appeals to people of all ages and who epitomizes science in action,” says Meisa Salaita, co-executive director of the Atlanta Science Festival, which will continue through March 25 with events throughout the metro area. “Who better than an astronaut to show us how science can take us to new and exciting places?”

The title of Kelly’s talk is “Endeavour to Succeed.” Tickets for the event can be bought in advance on the Atlanta Science Festival’s web site for $12 ($8 for children 12 and under). They will also be available at the door the day of the event for $15.

Starting at 5:30 pm, during the countdown to Kelly’s talk, the public is invited to join toy rocket launching activities on the Glenn Memorial lawn, led by members of the Georgia Tech Ramblin’ Rocket Club and the Institute of Electronic and Electrical Engineers.

Kelly, who began his NASA career in 1996, commanded the Space Shuttle Discovery, as well as the Endeavour. He left the astronaut corps in the summer of 2011 to help his wife, former U.S. Congresswoman Gabrielle Giffords, recover from gunshot wounds she received in an assassination attempt on her life. The couple’s story captivated the nation, and they went on to found Americans for Responsible Solutions to advocate for gun control.

NASA is comparing biological data from the Earth-bound Kelly with his identical twin brother, Scott Kelly, who recently spent a year in space. The unique Twins Study may offer insights into how to prepare astronauts for a long-term mission to Mars.

Kelly is also a prolific author, including numerous children’s books with space themes, and he will be available for a book signing following his talk at Emory.

The 12-day Atlanta Science Festival features talks, lab tours, film screenings, participatory activities and science demonstrations — more than 100 events at dozens of different venues, including the Emory campus. “We’ve expanded the number of days at the festival of the year, to avoid scheduling conflicts and give people a chance to experience more of the festival,” Salaita says. (Click here for the full schedule of events.)

Physics Live (at the Emory Mathematics and Science Center) and a Chemistry Carnival (at the Atwood Chemistry Center) will be among the Emory campus highlights, featuring lab tours and science demonstrations from 3:30 to 7 pm on Friday, March 24. (Click here for a full listing of Emory-related events.)

New at the festival this year will be an appearance by New York rap artist Baba Brinkman. He will perform “Rap Guide to Climate Chaos” at 1:30 on Saturday, March 18 at the Drew Charter School. 

Also new this year is “The Art and Science of Cooking with Insects,” featuring free tastings, at 7:30 pm on Thursday, March 23 at Manuels Tavern.

About 20,000 visitors are expected for the festival’s culminating event, the Exploration Expo, from 11 am to 4 pm on Saturday, March 25 at Centennial Olympic Park. Around 100 interactive exhibits will delight curious minds of all ages, from Emory chemist’s Doug Mulford’s “Ping Pong Big Bang” to the immersive Google Village experience.

Leading sponsors of this year’s Atlanta Science Festival include Emory, Georgia Tech, the Metro Atlanta Chamber, Delta Airlines and Google.

How will the shifting political winds affect U.S. climate policy?

Emory seniors Emily Li (left) and Jennie Sun were part of an Emory delegation to Marrakech, Morocco, in November for a U.N. Climate Change Conference. Shortly after the event began, Donald Trump, who has called climate change a hoax, won the U.S. presidential election. “We need to think about how to move forward," Li says, "because focusing on the negatives is ultimately not going to be useful.”

By Carol Clark

“No U.S. president has been as vocal about climate change, or as focused on mitigating it, as Barack Obama,” says Eri Saikawa, an assistant professor in Emory’s Department of Environmental Sciences and an expert in public policy and the science of emissions linked to global warming.

President-elect Donald Trump, however, has repeatedly called climate change a hoax.

“The concern about how Trump will deal with climate change is worldwide,” Saikawa says. “We all share the same atmosphere and the United States is a leading emitter of greenhouse gases. The impacts of global warming will affect the entire planet.”

Among Obama’s initiatives is the U.S. Clean Power Plan – which established the first national carbon pollution standards for power plants. U.S. leadership was also instrumental in the historic Paris Agreement to combat climate change. The 2015 agreement, organized by the United Nations’ Framework Convention on Climate Change (UNFCC), brought more than 190 countries together to commit to a framework to reduce greenhouse gas emissions.

“The Paris Agreement is an amazing achievement, and there was so much momentum and excitement surrounding it,” Saikawa says.

On November 7, delegates from around the world gathered in Marrakech, Morocco, to hammer out details resulting from the Paris Agreement. Saikawa headed a 10-member Emory delegation to Marrakech for the two-week event, known as the U.N. 22nd Conference of the Parties (COP 22). (Emory, one of the few universities approved as an official U.N. observer by the COP, also sent a delegation to the Paris talks last year.)

Emory’s Marrakech delegation included six students and three staff members. They split into two teams, with half participating at COP 22 during the first week and the other half during the second. 

Emory delegates on the ground in Marrakech, including senior Emily Li (front left), and, from upper left: Kate Lee (clinical fellow and staff attorney for the Turner Environmental Law Clinic), sophomore Maya Bornstein, senior Jennie Sun and Tyler Stern (an Emory grad who is now a Residence Life Fellow).

Emily Li, a senior majoring in environmental sciences and English, was there when the U.S. presidential election results were announced.

“Everyone was in shock,” Li says, of the surprise victory by Trump. “You could tell which delegates were from the U.S. because they just looked so tired that morning. The U.S. press office was total chaos.”

Li also struggled to take in the turn of events. “It was discouraging at first,” she says. “I’m really passionate about mitigating climate change and to have a national leader who doesn’t recognize it as an important issue is really disheartening.”

During the election campaign, Trump threatened to ax the Clean Power Plan and to pull the United States out of the Paris Agreement. After winning, Trump seemed to soften his stance somewhat, saying he would keep an “open mind” about the agreement. But he tapped Myron Ebell, a well-known climate-science denier, to lead his administration’s revamping of the Environmental Protection Agency (EPA).

Li summed up the post-election mood at COP 22 in a blog post called “Talking about the Elephant in the Room.” You can read it, along with posts by other members of the Emory delegation, on the Emory Climate Organization (ECO) web site, founded by students focused on understanding climate change.

The mood at COP 22 soon shifted from shock to a sense of renewed urgency. “A lot of the younger delegates, in particular, were saying how the Trump administration could help bring people together and motivate more engagement and action,” Li says. “We need to think about how to move forward because focusing on the negatives is ultimately not going to be useful.”

Local initiatives are more important than ever, she noted. For her senior thesis in environmental sciences, Li is zeroing in on ways that climate change may affect public health in Atlanta. “I’m doing a lot of research, looking at different studies to learn the scientific consensus. I’m also interviewing policy makers and people affected by events like the drought and the recent wildfires,” she says.

She plans to translate the science into engaging stories that she will post to a public web site, along with possible solutions. “I want to help communicate the direct effects of climate change on public health in Atlanta, so people living here can better understand the potential impact on themselves and their children,” Li explains. “I think that the more local an issue is, the more people tend to care about it.”

Geoff Martin, who is working on a master degree in environmental sciences, participated in the second week of COP 22. “In the month leading up to Morocco, I was really excited,” he recalls. “The Paris Agreement had finally gotten things moving in the right direction and I was going to this great event, COP 22, the first step towards implementation.”

The election results took the wind out of his sails, but only momentarily. “Being at the conference helped me regain my perspective,” Martin says. “People from all different levels and areas – government officials, those from the private sector and from non-governmental agencies – found reasons to still be hopeful.”

One of the major take-home messages for him is that the international community is going to continue to move forward in combating climate change, with or without the United States.

Another theme he heard repeatedly was that governing is a lot different from campaigning. “Trump will likely find that many of the things he said he was going to do during his campaign, like dismantle the EPA and cancel the Paris Agreement, may be easier said than done,” Martin says.

He also draws hope from the fact that the energy market is shifting. “The price of renewable energy keeps going down, making it increasingly competitive with fossil fuels in many places,” he says. “Regardless of government policy, the market could continue to drive a transition towards renewable energy.”

Martin is at work on a thesis, focused on analyzing the effectiveness of state-level climate and energy policies. He agrees with Li that the election of Trump could serve as a wake-up call for those concerned about climate change to take action at the local level, and not wait for the federal government to take the lead.

“Lots of talks at COP 22 were focused on sub-national efforts to mitigate climate change, not just in the United States, but throughout the world,” Martin says. He cites the Regional Greenhouse Gas Initiative, a successful cap-and-trade program for the power sector comprising nine U.S. states in the northeast.

The recent victory by the Standing Rock Sioux Tribe to block the $3.7 billion Dakota Access pipeline is another hopeful sign, Martin says. “Their victory was entirely a result of grassroots activism,” he says. “It shows how, if people really care about an issue and come out to protest and pressure government officials, they can make a difference.”

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

The top 10 policies needed now to protect pollinators

Bee thankful: “If you enjoyed a bountiful Thanksgiving Day dinner, you should give thanks to pollinators,” says Emory biologist Berry Brosi.

By Carol Clark

Scientific experts from eight different countries developed a list of the top 10 policies needed to reverse the decline of pollinators crucial to the world’s food supply.

The journal Science is publishing the recommendations for the global community in a forum article, “10 Policies for Pollinators.” The recommendations will be presented at the United Nations Convention of the Parties on Biological Diversity (CoP13), to take place in Mexico December 4 to 17.

“If you enjoyed a bountiful Thanksgiving Day dinner, you should give thanks to pollinators,” says Berry Brosi, a biologist and ecologist in Emory University’s Department of Environmental Sciences and a co-author of the article.

Brosi cites the first policy recommendation on the list as the most concrete and actionable: Better pesticide regulatory standards.

He adds that several of the recommendations related to sustainable agriculture more broadly include making chemical control for insects and other pests a last resort.

“Especially in light of the emergence of the Zika virus, and widespread public concern about mosquito-borne diseases, we are likely to see increased demands for pesticide use,” Brosi says. “Mosquito control is, of course, important, but we also need to be thoughtful about what kinds of pesticides we use and how we use them. We should carefully consider the impact on pollinators and other biodiversity.”

The Environmental Protection Agency is currently reviewing a class of insecticides commonly used in agriculture, neonicotinoids, which have been linked to wide-scale bee declines and impacts to other pollinator species by a range of scientific studies.

"Neonicotinoids are known to kill bees and other insect pollinators in very low doses, and to cause behavioral disruptions in even minute concentrations, measured in parts-per-billion," says Brosi, whose research focuses on both managed honeybees and wild bees.

In 2014, Emory began taking steps to eliminate the use of neonicotinoid-based pesticides and pre-treated plants on its campus grounds, the first university to do so worldwide.

The EPA’s review of the safety of neonicotinoids is not due until 2017.

The complete list of recommended policies for pollinators is as follows:

1. Raise pesticide regulatory standards
2. Promote integrated pest management
3. Include indirect and sublethal effects in GM crop risk assessments
4. Regulate movement of managed pollinators
5. Develop insurance schemes to help farmers
6. Recognize pollination as agricultural input in extension services
7. Support diversified farming systems
8. Conserve and restore “green infrastructure” (a network of habitats that pollinators can move between) in agricultural and urban landscapes
9. Develop long-term monitoring of pollinators and pollination
10. Fund participatory research on improving yields in organic, diversified and ecologically intensified farming

The policy recommendations follow a United Nations warning in February that pollinators were under threat. Brosi was among 77 international experts who worked on that report, the first global pollinator assessment for the U.N.’s Intergovernmental Panel for Biodiversity Ecosystem Services (IPBES).

The assessment found that more than 40 percent of invertebrate pollinator species, particularly bees and butterflies, face extinction. And 16 percent of vertebrate pollinators are under threat. The issue is critical to agricultural, economics and the health of humans and ecosystems: 75 percent of the world’s food crops depend on pollination by at least one of 20,000 species of pollinators, including bees, butterflies, moths, wasps, beetles, birds, bats and other vertebrates.

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Pollinators vital to food supply facing extinction, U.N. report warns 
Emory to ban bee-harming pesticides, protect pollinators

Learning to love our bugs

Each of us is a mobile ecosystem, teeming with trillions of living organisms. (Illustration by Giula Ghigini) 

By Jerry Grillo
Emory Medicine

They live on us and inside us, surround us like an invisible cloud, maintain and sustain us, ignore us, occasionally attack and kill us, and, ultimately, define us.

The human microbiome is made up of bacteria, fungi, viruses, and the like, and they cover every surface of our bodies.

"These microbiota are mostly in your gut, but also in your mouth, on your skin, in your lungs," says Emory biologist Nicole Gerardo. "They're playing critical roles in how you interact with the environment, how you process food, how you fight off pathogens, how you interact with drugs.

"Some of our remarkably fertile microbes are identical to those that live in other humans. But many are a distinct reflection of our individual experiences, shaped by who or what we've touched, where we've been, what we've breathed, and what we've consumed.

"Research interest in the human microbiome is exploding now," says Gerardo, who gave the introductory presentation at Emory's first microbiome symposium in November.

Spurred on by ambitious efforts like the National Institutes of Health's Human Microbiome Project, such research is demystifying the role of our myriad microbial passengers.

"It's like we're entering a new frontier of science, something that was basically ignored by medicine for a long time," says infectious disease researcher David Weiss, director of Emory's Antibiotic Resistance Center. "We're really at the beginning of studying all this, but I do think that in our lifetime, we'll be able to monitor each person's microbiome and intervene to improve their health. Looking at what type of bacteria we have and how resistant or sensitive they are to drugs will be an important part of health care. Most of the bugs we tote around are helpful, but they can also be ticking time bombs."

We may be able to someday diffuse the situation, replacing pathogenic microbes with a friendlier variety.

"There's great promise in manipulating the microbiome, in actually changing it," says geneticist Michael Zwick. "Actually, it's already happening."

Read the whole article in Emory Medicine.

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Companies pushing 'toddler milk' for 'growth' need oversight, experts warn

"Parents are commonly concerned about the size of their children and how well they are doing developmentally," says Emory's Michelle Lampl, MD, PhD, adding: "Not all kids who are smaller than average have a problem."

By Carol Clark

Liquid-based nutritional supplements, originally formulated for malnourished or undernourished children, need more regulatory oversight as they are increasingly marketed to promote growth in children generally, warn researchers at Emory University.

The journal Healthcare published their commentary article, citing the lack of scientific evidence to support marketing claims of the benefits for growth of giving healthy children liquid-based nutritional supplements, commonly known as “toddler milks.”

“A plumper baby is not necessarily a healthier baby,” says Michelle Lampl, who is the lead author of the article, director of the Center for the Study of Human Health at Emory University and an internationally recognized expert in human growth.

In fact, toddler milk supplements may actually be doing harm by fueling rapid, unnecessary weight gain in young children in the midst of a global obesity epidemic, she adds.

She notes that the liquid supplements may have as much as 240 calories per serving and have the potential to turn a healthy, lean toddler into an overweight one. “Healthy developmental growth does not mean gaining weight and getting fat,” she says. “It is primarily measured by whether a child is growing a stronger, longer skeleton.”

Liquid-based nutritional supplements fall into a regulatory loophole, because the Food and Drug Administration (FDA) does not consider supplements to be a drug or a “conventional” food. “When a mother goes into a store and sees a toddler milk supplement on a shelf, she has no idea that it falls into a less rigorous FDA category than those covering so-called conventional food and medicine,” Lampl says. “We have a product aimed at a vulnerable population – infants and young children – that does not have adequate oversight.”

Co-authors of the commentary article are: Meriah Schoen, a research assistant at Emory’s Center for the Study of Human Health and a graduate student focused on nutrition at Georgia State University; and Amanda Mummert, who recently received a PhD in Anthropology from Emory's Laney Graduate School.

The commentary appears in a special issue of Healthcare, dedicated to the physician-scientist David Barker, who died in 2013. He originated the Barker Hypothesis, also known as the Developmental Origins of Health and Disease model, linking fetal and early infant experiences to an individual’s health status across the lifespan.

“David Barker opened the door to the importance of early influences, including nutrition and other environmental factors, for lifelong health,” Lampl says. “He believed that we have an ethical responsibility to ensure that the next generation is as healthy as it can be.”

Companies have marketed infant formulas for decades. In 1981, however, the World Health Organization (WHO) voted to recommend banning marketing of formulas for babies under six months, since the formulas were associated with lower rates of breastfeeding, and increased disease and malnutrition in the developing world.

Countries around the world adopted the rules and breastfeeding rates went up globally. The formula industry responded by focusing on toddler milk supplements, aimed at children ages six months and up.

Liquid-based supplements containing vitamins and minerals may be beneficial to children that are malnourished, or suffering from chronic diseases that prohibit their ability to consume solid foods, Lampl says. The problem, she adds, is that toddler milks have grown into a multi-billion-dollar industry that is expanding internationally to encompass healthy children.

Rapidly boosting the weight of children who are simply smaller than average but healthy could have lifelong consequences, she says. Barker, for instance, found a direct link to higher rates of metabolic disorders among individuals who were born relatively small and grew rapidly in the first few years of life.

“Parents are commonly concerned about the size of their children and how well they are doing developmentally,” Lampl says, adding that the growth charts used in pediatrician offices are often misunderstood. “Not all kids who are smaller than average have a problem.”

Busy mothers on the go, who may be consuming “energy drinks” and liquid supplements themselves, are primed to buy toddler milk for young children under the assumption that they are healthy choices, particularly for children who may be picky eaters.

“Although it can take a picky eater up to 20 times of trying a food to decide if they like it, most mothers offer a food fewer than five times before switching to something more convenient,” Lampl says. “It’s much easier to hand your child a sugary ‘toddler milk,’ thinking it’s healthy and it helps them grow.”

The WHO is set to consider recommendations concerning calorie amounts and ingredients for liquid-based nutritional supplements marketed to toddlers and older children during a meeting in early December.

Those recommendations will not have teeth, however, and it will be up to individual governments whether they decide to adopt them and enforce them.

“We are really behind when it comes to regulatory oversight for the marketing of these supplements, and for rigorous scientific research showing the impact of their widespread use on children,” Lampl says.

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Grandma was right: Infants wake up taller

Emory's Rolosense wins bronze in Collegiate Inventors Competition

Emory graduate student Aaron Blanchard, left, and Kevin Yehl, who recently received his PhD in chemistry from Emory, were awarded bronze medals at the recent Collegiate Inventors Competition in Washington D.C. (Photo by the National Inventors Hall of Fame.)

By Carol Clark

Emory University’s Rolosense – the first rolling DNA motor – took the bronze medal in the graduate division of the 2016 Collegiate Inventors Competition, held recently in Washington D.C.

The Rolosense, and its application as a chemical sensor, was developed in the lab of Emory chemist Khalid Salaita by his students Aaron Blanchard and Kevin Yehl. Blanchard is a PhD student in Emory’s Laney Graduate School and the Coulter Department of Biomedical Engineering (BME) at Georgia Tech and Emory, while Yehl recently received his PhD in chemistry from Emory.

The Rolosense is the biological equivalent of the invention of the wheel for the field of DNA machines. “It’s a completely new approach at using DNA motors for sensing and diagnostics,” Yehl says. “We now hope to keep broadening the scope of the technology and really prove it out in the field.”

The Rolosense is 1,000 times faster than other synthetic DNA motors. Its speed, which is powered by ribonuclease H, means a simple smart phone microscope can capture its motion through video.

Watch a video to learn more about the rolling DNA motor:


The researchers have filed an invention disclosure patent for the concept of using the particle motion of the rolling molecular motor as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water. It offers a way of doing low-cost, low-tech diagnostics for researchers working in settings with limited resources, or for consumers themselves.

Yehl and Blanchard were one of six teams of graduate students that competed in early November in the finals at the National Inventors Hall of Fame in Washington D.C. The Collegiate Inventors Competition is considered the foremost program in the country encouraging invention and creativity in undergraduate and graduate students. The entries of the elite student teams represent the most promising inventions from U.S. universities.

The judges included inductees to the National Inventors Hall of Fame, officials from the U.S. Patent and Trademark Office and scientists from the global healthcare firm AbbVie.

“It was really cool to meet students from the other teams, and also the judges, to get their feedback,” Yehl says.

His main takeaway message: Keep on inventing.

Yehl is taking that advice to heart. In his new position as a post-doctoral associate in a synthetic biology lab at MIT, he’s now working on novel therapeutics to target drug resistant bacteria.

Blanchard agrees that a highlight of the competition was networking with the other competitors and the judges. “Several of the judges encouraged me to focus on areas of research that I’m passionate about, and not just choose things to pad my resume,” he says. “The judges are inventors themselves and, in some cases, they’ve had an impact on millions of people, so their input is important to me. I really took a lot away from the competition besides a bronze medal.”

The National Inventors Hall of Fame does outreach around the country. Blanchard says he hopes to get involved in future outreach projects in his hometown of El Paso, Texas. “It’s an amazing city,” he says, because it’s in the United States but is predominantly Hispanic. You encounter many different types of people and that helps drive adaptability and creativity. Unfortunately, it’s also geographically and culturally isolated so it’s harder for students to obtain exposure to scientific research. El Paso produces some great minds with great potential to make a difference in science, technology, engineering and math disciplines. I think it’s important to give kids there more exposure to STEM fields so they have an idea of the possibilities.”

Meanwhile, Blanchard and Yehl will continue developing the Rolosense with Salaita.

“We have this phenomenal technology that can make a difference in the world and we want to keep moving forward with it,” Blanchard says.

Related:
Emory's 'Rolosense' rolling to finals of Collegiate Inventors Competition
Nano-walkers take speedy leap forward with first rolling DNA motor

BRAIN grant to fund study of how the mind learns

Biophysicist Ilya Nemenman, left, is developing theories about the brain that can be tested in the lab of biologist Sam Sober, right. (Emory Photo/Video).

By Carol Clark

How does the brain correct mistakes and guide the process of learning a skill? Why do some individuals learn faster than others?

Two Emory researchers – biophysicist Ilya Nemenman and biologist Sam Sober – recently received a $1 million grant from the National Institutes of Health BRAIN Initiative to explore these questions through a theoretical-experimental framework. Their research into how the sensory-motor loop controls and optimizes learning could lead to better protocols to help those dealing with major disruptions to their learned behaviors, such as when recovering from a stroke.

The BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) was launched by President Obama in 2014 as part of a widespread effort to gain fundamental insights for treating a range of brain disorders.

Emory has received other grants from the BRAIN Initiative: In 2015, a $1.7 million award went to neuroscientists Dieter Jaeger (Department of Biology) and Garrett Stanley (Emory-Georgia Tech’s Wallace H. Coulter Department of Biomedical Engineering). They will use the award to explore neural circuits related to sensing and physical action. In 2016, neurosurgeon Robert Gross in the School of Medicine received a $5 million grant to focus on optimizing neurostimulation therapies for epilepsy.

The grant received by Nemenman and Sober is part of a new cohort, opening another phase of the BRAIN Initiative: The development of theoretical, computational and statistical tools.

“Big data by itself is not useful,” Nemenman says. “We also need to come up with methods for understanding such data.”

Nemenman is working on a theory to help explain how the brain learns. “If you are learning something similar to something that you already know, it’s easier than if you are learning something entirely new,” he says. “We see this effect across the animal kingdom, including in humans. And this ability to learn something new changes with age.”

He gives the example that he will always speak English with an accent, since he is a native of Belarus and did not move to an English-speaking country until shortly before he became a student at Princeton. His children, however, will speak English without an accent since they were born in the United States and immersed in English from birth.

Nemenman is collaborating with Sober, who conducts experiments with Bengalese finches. “These songbirds are one of the best model systems available for studying how the brain learns to communicate,” Sober says.

The male songbirds sing to attract a mate, but they are not born with this ability, Sober explains. Instead, the young males learn to sing by memorizing, and then imitating, the singing of their fathers. When a young bird sings the wrong note, it tries to correct its mistake to match the memorized “target” sound.

In experiments, the Sober lab places tiny earphones on a songbird. When the bird sings, the researchers distort some of the notes slightly and play back the sound through the earphones. The bird is tricked into thinking it has sung a note incorrectly and tries to correct it.

Through this method, the lab has found that the birds are able to correct small distortions of sound, but they cannot correct large distortions.

“Many errors are distributed as a bell-shaped curve, but the distribution of singing errors in the birds is not bell-shaped,” Nemenman says. He is developing theories to explain how the difficulty of learning and correcting for large disturbances is related to this peculiar shape of the distribution of errors produced by the brain during learning.

“We can test the theories through experiments and learn more about the process,” he says. “The ultimate goal is to develop predictive models of how individuals learn from their errors that can be extended to other organisms, including humans.”

Nemenman also recently received a grant from the Kavli Foundation, to support workshops, symposiums and journal clubs that foster interdisciplinary theoretical and computational approaches to neuroscience, and bridge researchers at Emory and Georgia Tech.

It is important for physicists to share their expertise and collaborate with other scientists focused on understanding the brain, Nemenman says. As chair of the American Physical Society’s division of biological physics, he strives to establish programs that attract young physicists to neuroscience.

“Physicists are well posed to have a dramatic impact in this area,” he says. “We are trained to do science by combining theory and experiments. We can apply the same techniques to study the brain that we use to study other mysteries of the universe. Many graduate students in physics who came in intending to work on string theory, like I did, are coming out with a PhD focused on theoretical neuroscience.”

Related:
How songbirds learn to sing 
Biology may not be so complex after all

Biology professor holds meetings on the run

Emory biology lecturer Patrick Cafferty (left, blue shorts and shirt) takes one of his weekly office hours on the road for a three-mile run through campus. Emory Photo/Video

By April Hunt
Emory Report

There’s a very good chance Patrick Cafferty runs a different meeting than you do.

The Emory University biology lecturer takes one of his weekly office hours on the road, heading out for a three-mile run through campus with students. It’s part of an overarching goal to truly connect with students in his human physiology class as a teacher and mentor.

“I invite every student to just come in and chat,” says Cafferty, decked out in running shorts and a tank top before one of the weekly runs. “Some are too shy to do it, but they can join a run and just listen, and we get to know each other on a personal level. There is an equalizing aspect of sport.”

Early in the semester, Cafferty is the one doing most of the talking. Part of that is his 10-minute mile pace — slow for a serious triathlete like him but a challenge for some students. But it also lets Cafferty discuss class topics, such as the neurobiology behind cramped muscles or the dilatation of blood vessels serving muscles during exercise, as they are happening to some of the runners.

“This is great for me, because it’s an outlet to exercise, study and develop a relationship with faculty and students all at once,” says Amancio Romero, a junior behavioral biology and neuroscience major who last ran regularly, as a sprinter, in high school.

Call it active learning, something Cafferty has experienced personally. He grew up in Canada, interested first in exploring wildlife and later, studying life from the molecular level. At the same time he grew to understand complex cellular behavior from a biology perspective, he was applying those lessons to his training in Iron Man competitions and cycling. But it was not until graduate school at McGill University in Montreal, when he joined a swim club that welcomed students, staff and faculty, that he realized the value of linking those two worlds.

At McGill, Cafferty ended up in the pool with some professors he never would have otherwise met. He also connected with a professor who ended up being a doctoral mentor.

“There is a reason we have business meetings at lunch or over golf. It’s about being comfortable and being able to have natural conversations,” Cafferty says.

Those realizations prompted Cafferty to launch a run club when he came to Emory as a faculty-in-residence in 2011. Students, faculty and community members participated in that club, which became the model for what he calls his Active Office Hours.

Students who have participated so far include an Emory swimmer who gave up the sport to make time for studying, students who last ran during high school track or cross country, and even one person who had never run before.

One of the students has joined while listening to Cafferty’s lectures on an MP3 device, asking questions as they arise in his headphones.

Another, senior Maiya Smith, came with a screenshot of questions to ask Cafferty during the run through Lullwater Preserve.

“I never heard of a professor doing this before, and I love it,” says Smith, an anthropology and human biology major who ran marathons in high school. “I can see our runs directly connecting to class, and that just makes me want to ask even more questions.”

Like typical desk-bound office hours, the active versions are also a valuable resource for students beyond the classroom.

Cafferty welcomes students outside his class to the runs. He also plans on interval training runs, which will help some runners improve their times while letting everyone regroup to chat.

Conversations vary from campus gossip to current TV shows to classroom lessons, he says. Inevitably, questions come up about fitness or diet trends, issues directly linked to classroom work on nutrition and exercise.

“Running is completely new to me,” says Luke Roberts, a junior biology major who spent a year on Emory’s swim team. “I don’t have any breath left to ask questions, but it’s interesting just to listen and put it all together.”

The benefits spill over to students who don’t want to run, too. More of those students appear to have noticed Cafferty’s passion for biology in general and physiology in particular, and they are showing up more often in his Rollins Research Center office to talk.

“I hope to share something I’m kind of good at and enjoy with them, because I want them to know me,” Cafferty says. “And I think students see if you have a genuine interest in getting to know them.”

Emory's 'Rolosense' rolling to finals of Collegiate Inventors Competition

“I think the advantage we have with our technology is that it's so simple," says Aaron Blanchard, left (a PhD student in Emory's Laney Graduate School and Coulter Department of Biomedical Engineering at Georgia Tech and Emory), shown using the Rolosense with his advisor, Emory chemist Khalid Salaita. 

By Carol Clark

The first rolling DNA motor – the biological equivalent of the invention of the wheel for the field of DNA machines – is headed from its origins in an Emory University chemistry lab to the finals of the 2016 Collegiate Inventors Competition in Washington D.C.

Kevin Yehl and Aaron Blanchard make up one of six teams of graduate students who will be flown to the finals in early November. Yehl and Blanchard developed the DNA motor (dubbed Rolosense), and its application as a chemical sensor, in the laboratory of their advisor – Emory chemist Khalid Salaita.

Blanchard is a PhD student in Emory's Laney Graduate School and the Coulter Department of Biomedical Engineering (BME) at Georgia Tech and Emory, while Yehl recently graduated from Emory with a PhD in chemistry.

The entries of the elite student teams represent the most promising inventions from U.S. universities. “Their ideas will shape the future,” wrote Michael Oister, CEO of the National Inventors Hall of Fame, in a letter announcing the finalists.

The Collegiate Inventors Competition annually gives out about $100,000 in cash prizes and is considered the foremost program in the country encouraging invention and creativity in undergraduate and graduate students. The competition also promotes entrepreneurship, by rewarding ideas that hold value for society.

The Rolosense is 1,000 times faster than any other synthetic DNA motor. Its speed means a simple iPhone microscope can capture its movement through video, giving it potential for real-world applications, such as disease diagnostics.

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

"It's exciting," Yehl says. "Previous winners have gone on to start companies with their inventions and become successful scientists. It will be great to get feedback from the judges on the Rolosense."

The judges will include inductees to the National Inventors Hall of Fame, officials from the U.S. Patent and Trademark Office, and scientists from the global healthcare firm AbbVie.

Some of the best discoveries involve serendipity, and that was the case for the Rolosense. Yehl was working last year as a post-doctoral fellow in the Salaita lab, which specializes in visualizing and measuring mechanical forces at the nano-scale. He was conducting experiments using enzymatic nano-particles – micron-sized glass spheres. “We were originally just interested in understanding the properties of enzymes when they’re confined to a surface,” Yehl says.

During the experiments, however, he learned by accident that the nano-particles roll. That gave him the idea of constructing a rolling DNA-based motor using the glass spheres.

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. 

So far, however, mankind’s efforts have fallen far short of nature’s myosin, which speeds effortlessly about its biological errands. Some synthetic nano-walkers move on two legs. They are essentially enzymes made of DNA, powered by the fuel 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.

 A cell phone app is in the works.

The Rolosense design mows over these limitations. 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.

“The Rolosense can travel one centimeter in seven days, instead of 20 years, making it 1,000 times faster than other synthetic DNA motors,” Salaita says. “In fact, nature’s myosin motors are only 10 times faster than the Rolosense, and it took them billions of years to evolve.”

The researchers next demonstrated the Rolosense could be used to detect a single DNA mutation by measuring particle displacement. Yehl simply glued lenses from two inexpensive laser pointers to the camera of an iPhone to turn the phone’s camera into a microscope and capture videos of the particle motion.

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

Nature Nanotechnology published the work on the rolling DNA motor. The researchers have filed an invention disclosure patent for the concept of using the particle motion of the Rolosense as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water.

Yehl has since left Emory for a position at MIT, but he continues to work with Salaita and Blanchard on refining the Rolosense.

Blanchard, who has a background in computer coding, is integrating the data analysis of the Rolosense into a smart phone app that will provide a readout of the results.

“I feel really fortunate as a graduate student to be working on this project,” Blanchard says. “As the molecular detection field grows, I think that Rolosense will grow with it.”

For their demonstration during the finals, Yehl and Blanchard plan to hand the judges smart phones and samples of water (including some containing lead), and let the judges use Rolosense to test the samples.

“It can be easy to dazzle with complex technologies like a robot,” Blanchard says, “but I think the advantage that we have with our technology is that it’s so simple. We can let the judges see for themselves how they can use Rolosense to quickly learn something useful, like whether a water source is contaminated with a heavy metal.”

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Nano-walkers take speedy leap forward with first rolling DNA motor
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Molecular beacons shine light on how cells crawl

Cardinals may reduce West Nile virus spillover in Atlanta

One more reason to love the northern cardinal: In addition to being beautiful to look at, in Atlanta these birds appear to help shield humans from West Nile virus. (Photo by Stephen Wolfe.)

By Carol Clark

Northern cardinals act as “super suppressors” of West Nile virus in Atlanta, slowing transmission and reducing the incidence of human cases of the mosquito-borne pathogen, suggests a new study published in the American Journal of Tropical Medicine and Hygiene.

“Previous research has shown that the American robin acts like a ‘super spreader’ for West Nile virus in Chicago and some other cities,” says Rebecca Levine, who led the research as a PhD student in Emory University’s Department of Environmental Sciences. “Now our study provides convincing data that northern cardinals and some other bird species may be ‘super suppressors’ of the virus in Atlanta.”

The researchers also found that birds in Atlanta’s old-growth forests had much lower rates of West Nile virus infection compared to birds tested in the city’s secondary forests and other urban micro-habitats.

“This finding suggests that old growth forests may be an important part of an urban landscape,” Levine says, “not just because of the natural beauty of ancient trees, but because these habitats may also be a means of reducing transmission of some mosquito-borne diseases.”

Levine has since graduated from Emory's Laney Graduate School and now works as an epidemiologist and entomologist for the Centers for Disease Control and Prevention.

Uriel Kitron, chair of Emory’s Department of Environmental Sciences and an expert in mosquito-borne pathogens, is senior author of the paper.

Rebecca Levine in the field with one of the cardinals that was tested. The birds in the study were captured with mist nets and released unharmed after blood samples were drawn. (Photo courtesy of Rebecca Levine.)

West Nile virus (WNV) is zoonotic, meaning that it is an infection of animals that can spill over to humans by a bridge vector, in this case Culex mosquitos. Since its introduction to the United States in 1999, WNV has become the most common zoonotic mosquito-borne pathogen in the country, infecting an estimated 780,000 people (including more than 1,700 fatal cases), in addition to birds and other mammals, such as horses.

The Kitron lab wanted to find out why Georgia’s infection rate for WNV since 2001 is relatively low, at about 3.3 cases per 100,000 people, compared to some states in the north. A 2002 outbreak in Illinois, for instance, recorded about 7.1 cases per 100,000 people.

“When West Nile virus first arrived in the United States, we expected more transmission to humans in the South,” Kitron says, “because the South has a longer transmission season and the Culex mosquitos are common. But even though evidence shows high rates of the virus circulating in local bird populations, there is little West Nile virus in humans in Atlanta and the Southeast in general.”

During the three-year study, the research team collected mosquitoes and birds from different sites across Atlanta, tested them for WNV, and ran a DNA analysis of the mosquitos’ blood meals to see which species of birds they had bitten.

“We found that the mosquitoes feed on American robins a lot from May to mid-July,” Levine says. “But for some unknown reason, in mid-July, during the critical time when the West Nile virus infection rate in mosquitos starts going up, they switch to feeding primarily on cardinals.”

American robins do a great job of amplifying the virus in their blood once they are infected. That trait means they can more efficiently pass the virus to other mosquitos that bite them, so robins are known as “super spreaders.” The virus does not efficiently reproduce, however, in the blood of northern cardinals.

“You can think of the cardinals like a ‘sink,’ and West Nile virus like water draining out of that sink,” Levine says. “The cardinals are absorbing the transmission of the virus and not usually passing it on.”

The study results showed that, to a somewhat lesser extent, birds in the mimid family – including mockingbirds, brown thrashers and gray catbirds – also appear to be acting like sinks for WNV in Atlanta.

The researchers found significantly fewer avian WNV infections in the old growth forest sites sampled in Atlanta – including Fernbank Forest and Wesley Woods Preserve – compared to secondary forests such as Grant Park and the Atlanta Botanical Garden. The rate of infections in mosquitos, however, was similar for both types of forests.

“These are really complex ecosystems, so we cannot single out the specific reasons for these findings,” Levine says. “They suggest that there is something unique about these old growth forests and how they affect avian systems in Atlanta.”

Atlanta, nicknamed “City in the Forest,” is one of only seven U.S. cities with a high population density to have urban tree cover of 40 percent or more. In contrast, Chicago retains only 11 percent tree cover.

“As new mosquito-borne diseases enter and spread in America, we need to better understand all aspects of pathogen transmission cycles, said Stephen Higgs, present of the American Society of Tropical Medicine and Hygiene. “By shedding light on the reasons behind a curious discrepancy in West Nile virus human infection rates in different regions of the United States, this study has the potential to better protect Americans’ health while continuing to demonstrate the link between animal and human health.”

Co-authors of the paper also include researchers from the University of Georgia, Texas A&M and the Georgia Department of Transportation’s Office of Environmental Services.

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Chasing fire: Fever and human mobility in an epidemic

Dengue fever is common in Iquitos, Peru, a densely packed city surrounded by the Amazon. With the imminent arrival of Zika virus to Iquitos, the researchers expect that the data they have collected on dengue transmission will also add to the understanding of how Zika spreads through a population.

By Carol Clark

Disease ecologists working in the Amazonian city of Iquitos, Peru, have quantified for the first time how a fever affects human mobility during the outbreak of a mosquito-borne illness. The findings were published by Proceedings of the Royal Society B.

“When you are sick with dengue, or another illness causing fever, your behavior can change,” says Gonzalo Vazquez-Prokopec, an assistant professor in Emory University’s Department of Environmental Sciences, and senior author of the study. “We’ve found that people with a fever visit 30 percent fewer locations on average than those who do not have a fever, and that they spend more time closer to home. It may sound like stating the obvious, but such data have practical applications to understand how human behavior shapes epidemics. No one had previously quantified how a symptom such as fever changes mobility patterns, individually and across a population, in a tropical urban setting like Iquitos.”

An issue in tracking an infectious disease like dengue, chikungunya and Zika is that most of the people infected are asymptomatic, or do not have symptoms severe enough to trigger a doctor visit. “They may not feel sick at all, and yet they could be infecting others, which could help explain how these pathogens move explosively across a population,” Vazquez-Prokopec says. “We need to rethink the way we do disease surveillance and control if asymptomatic people are important drivers of transmission.”

Trying to control the spread of a disease is like chasing a fire, he adds. “You know that a fire may be at the home of a sick person but, using the data we have for current models, you don’t really know where the fire is going next.”

About 550 people from Iquitos participated in the study. They included subjects who did not have a fever at the time of the study and those who did. The feverish subjects were also divided into those who tested posted for dengue and those who did not. Data on the movement of participants was collected through interviews and validated using wearable global positioning system loggers.

The study was part of a major research project in Iquitos, which began in 2008, to study the ecology of dengue fever. Dengue is spread by the Aedes aegypi mosquito, the same species that spreads the chikungunya and Zika viruses.

With the imminent arrival of Zika virus to Iquitos, the researchers expect that the data they have collected on dengue transmission will also add to the understanding of how Zika and chikungunya spread through a population.

During the first phase of the project, the researchers showed that human movement is a major driver of the spread of a vector-borne disease like dengue in an urban environment. They are now trying to learn more details about how symptoms and behavior are coupled to drive disease outbreaks.

Symptoms of people infected with a disease fall on a continuum, from no symptoms at all, to so severe they are hospitalized. For the current study, the researchers focused on the impacts of fever, since it is a classic marker of disease, and it is objective and easy to quantify.

The researchers are continuing to investigate how variation in symptoms of illness affects human mobility, using both objective and subjective signs, to refine the data and hone in on more detailed patterns of disease transmission.

“The more we learn about the role of human movement in the transmission of a mosquito-borne disease, the more we realize that we need to change the way we approach controlling these diseases,” Vazquez-Prokopec says.

The Iquitos project is supported by funding from the U.S. National Institutes of Health and the Department of Homeland Security. Co-authors of the study include researchers from the University of Notre Dame, the University of California, Davis, the National Institutes of Health, Tulane University, the Universidad Peruana Cayetano Heredia in Peru, Andrews University and San Diego State University.

Related:
Zeroing in on 'super spreaders' and other hidden patterns of epidemics
Human mobility data may help curb epidemics

Adding anthropology to genetics to study ancient DNA

Kendra Sirak, an Emory PhD candidate in anthropology, is working as a visiting researcher at the Earth Institute at University College Dublin.

By Leslie King
Emory Report

Kendra Sirak, a PhD candidate in anthropology in the Laney Graduate School, is currently working in Ireland, testing the DNA of people ranging from medieval Nubians to an ancient Chinese specimen to an Irish rebel.

Originally from the small town of Dallas, Pennsylvania, Sirak attended Northwestern University on an athletic scholarship for field hockey. "Starting out in psychology, I was inspired by an amazing young professor and became hooked after writing a research paper about the allegedly extinct subspecies Homo sapiens idaltu," Sirak recalls. "I wanted to study the past of humanity so I added anthropology for a double major."

Sirak came to Emory in 2012, drawn by the opportunity to work with George Armelagos, Goodrich C. White Professor of Anthropology (who passed away in 2014).

"I emailed George, who was one of the gods of anthropology, not expecting an answer," she says. "He responded in 37 minutes."

Now, Sirak is working as a visiting researcher at the Earth Institute at University College Dublin. Her research has also taken her to Russia, Hungary, Romania, China, India and Italy to access DNA in human skeletons and train other researchers in those techniques.

In an interview from Ireland, Sirak talks about her work and how she came to add genetics to anthropology, resulting in fascinating research and career paths.

What led you to add genetics to anthropology? 

I had no interest in genetics, being totally dedicated to the study of human osteology and paleopathology. But George [Armelagos] believed DNA was going to become a critical part of anthropological research — and he couldn’t have been more right.

He proposed that I take some Nubian skeletal remains he had excavated in the 1970s to Ireland and learn how to do ancient DNA analysis at Trinity College Dublin.

I went home and cried because I didn’t want to say no, but I really, really did not want to go. However, I decided to just go anyway. It was the best academic decision I could have ever made. I stepped into the ancient DNA lab at Trinity and realized that I had been spelling “chromosome” wrong for as long as I could remember, which was where my knowledge of DNA was then.

What do you gain by combining anthropology with genetics in your research?

Genetics provides really fantastic, concrete data. However, it doesn’t provide the context that anthropology does. I like to think of genetics giving me the hard scientific data that I want, but anthropology adding in the human context and making the molecular data a human reality.

At Emory, I have learned how to think from a “biocultural” point of view. While many other anthropology programs stress only either a “biological” or a “cultural” approach, Emory combines the two.

I study the biology of past populations and I think about the way their culture and social environment could have influenced individual health and well-being, population demographics, patterns of morbidity and mortality, etc.

What have you been working on in Ireland? 

Primarily extracting and sequencing DNA from skeletal remains from two socially disparate medieval cemeteries at the site of Kulubnarti in Sudanese Nubia. I am also part of a collaboration between University College Dublin and Harvard Medical School’s Department of Genetics lab.

We were recently contacted by the Irish National Police to help identify the remains of Thomas Kent, executed by the British for his part in the Easter Rising insurrection in 1916 and buried in a shallow grave on the grounds of Cork Prison; however, his body could not be positively identified. Collaborating with another team, we came up with this novel method to compare genetic data collected from two of Kent’s known living relatives and confirm his identity. He was given an honorable burial and a big state parade.

What other projects do you have in the works? 

We hope to become involved in the Duffy’s Cut Project. Duffy’s Cut is the location of railroad tracks west of Philadelphia built by 57 Irish immigrants in the mid-1800s. All 57 are thought to have died from cholera. However, forensic evidence suggests that some might have been murdered, perhaps because of fear of contagion. We are hoping a DNA analysis on these samples will help identify these men and their family relationships.

We are in conversation with an Irish human rights group about identifying the remains of more than 800 Irish babies uncovered in a mass grave in western Ireland. This grave was a consequence of the period when it was not socially acceptable for a woman to have a baby out of wedlock. The ultimate goal would be a database of the unidentified infants’ genetic information. Then people who believe they might have some relative in this mass grave could be tested for a genetic match. This project was presented at the United Nations.

What are your post-Emory plans and goals?

My goal is to start writing my dissertation, a bioethnography of the ancient Nubians, this fall and be graduated from Emory in June 2018. Post-Emory, I can see myself applying for a postdoc position to expand my research, or I might like to get involved with scientific communication to the lay public. After taking a human genetics course taken at Emory, I’m really interested in genetic counseling. I’ve been thinking about becoming a certified genetic counselor.

What do you like to do in your “off” time? 

I am a world traveler, marathon runner and craft beer connoisseur. Studying anthropology and working in ancient DNA has given me incredible opportunities to travel around the world to collect samples for our analyses.

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