The search for secrets of ancient remedies

Cassandra Quave is a world leader in the field of medical ethnobotany — studying how indigenous people used plants in their healing practices to identify promising candidates for modern drugs.

Cassandra Quave (it rhymes with “wave”) is an assistant professor in Emory’s Center for the Study of Human Health and in the School of Medicine’s Department of Dermatology. She is also a member of the Emory Antibiotic Resistance Center.

The Florida native looks at home in the sweltering heat of South Georgia, standing behind a pick-up truck parked on a dirt road that winds through a longleaf pine forest. She tilts a straw cowboy hat back from her face and waves off a flurry of gnats. Her utility belt bristles with shears and a hunting knife. The unfolded gate of the truck bed serves as her desk, as she wrangles a leafy vine of passionflower into a wooden plant press.

 “The Cherokee pounded the roots of passionflower into a poultice to draw out pus from wounds, boils and abscesses,” Quave says. “Everywhere I look in this ecosystem I see plants that have a history of medicinal use by native peoples. The resin of the pine trees all around us, the fronds from the ferns beneath them and the roots of those beautiful yellow flowers over there — black-eyed Susans — were all used to treat wounds and sores.”

Read more here about Quave's field work this summer, and the undergraduates who helped her collect plants of importance to Native Americans.

Neuroscientists team with engineers to explore how the brain controls movement

The labs of Georgia Tech's Muhannad Bakir (far left) and Emory's Samuel Sober (far right) combined forces for the project. The work will be led by post-doctoral fellows in their labs, Georgia Tech's Muneeb Zia (center left) and Emory's Bryce Chung (center right). Photos by Ann Watson, Emory Photo/Video.

By Carol Clark

Scientists have made remarkable advances into recording the electrical activity that the nervous system uses to control complex skills, leading to insights into how the nervous system directs an animal’s behavior.

“We can record the electrical activity of a single neuron, and large groups of neurons, as animals learn and perform skilled behaviors,” says Samuel Sober, an associate professor of biology at Emory University who studies the brain and nervous system. “What’s missing,” he adds, “is the technology to precisely record the electrical signals of the muscles that ultimately control that movement.”

The Sober lab is now developing that technology through a collaboration with the lab of Muhannad Bakir, a professor in Georgia Tech’s School of Electrical and Computer Engineering. The researchers recently received a $200,000 Technological Innovations in Neuroscience Award from the McKnight Foundation to create a device that can record electrical action potentials, or “spikes” within muscles of songbirds and rodents. The technology will be used to help understand the neural control of many different skilled behaviors to potentially gain insights into neurological disorders that affect motor control.

“Our device will be the first that lets you record populations of spikes from all of the muscles involved in controlling a complex behavior,” Sober says. “This technique will offer unprecedented access to the neural signals that control muscles, allowing previously impossible investigations into how the brain controls the body.”

“By combining expertise in the life sciences at Emory with the engineering expertise of Georgia Tech, we are able to enter new scientific territory,” Bakir says. “The ultimate goal is to make discoveries that improve the quality of life of people.”

A prototype of the proposed device has 16 electrodes that can record data from a single muscle. The McKnight Award will allow the researchers to scale up to a device with more than 1,000 electrodes that can record from 10 or more muscles.

The Sober lab previously developed a prototype device — electrodes attached to flexible wires — to measure electrical activity in a breathing muscle used by Bengalese finches to sing. The way birds control their song has a lot in common with human speech, both in how it is learned early in life and how it is produced in adulthood. The neural pathways for birdsong are also well known, and restricted to that one activity, making birds a good model system for studying nervous system function.

“In experiments using our prototype, we discovered that, just like in brain cells, precise spike timing patterns in muscle cells are critical for controlling behavior — in this case breathing,” Sober says. 

The prototype device, however, is basic. Its 16 electrodes can only record activity from a single muscle — not the entire ensemble of muscles involved in birdsong. In order to gain a fuller picture of how neural signals control movement, neuroscientists need a much more sophisticated device.

The McKnight funding allowed Sober to team up with Bakir. Their goal is to create a micro-scale electromyography (EMG) sensor array, containing more than 1,000 electrodes, to record single-cellular data across many muscles.

The engineering challenges are formidable. The arrays need to be flexible enough to fit the shape of small muscles used in fine motor skills, and to change shape as the muscles contract. The entire device must also be tiny enough not to impede the movement of a small animal.

“Our first step is to build a flexible substrate on the micro-scale that can support high-density electrodes,” Bakir says. “And we will need to use microchips that work in parallel with 1,000 electrodes, and then attach them to that substrate.”

To meet that challenge, the Bakir lab will create a 3D integrated circuit. “Essentially, it’s building a miniature skyscraper of electrical circuits stacked vertically atop one another,” Bakir says. This vertical design will allow the researchers to minimize the size of the flexible substrate.

“To our knowledge, no one has done what we are trying to do in this project,” Bakir says. “That makes it more difficult, but also exciting because we are entering new space.”

The Sober lab will use the new device to expand its songbird vocalization studies. And it will explore how the nervous system controls the muscles involved when a mouse performs skilled movements with its forelimbs.

An early version of the technology will also be shared with collaborators of the Sober lab at three different universities. These collaborators will further test the arrays, while also gathering data across more species.

“We know so little about how the brain organizes skilled behaviors,” Sober says. “Once we perfect this technology, we will make it available to researchers in this field around the world, to advance knowledge as rapidly as possible.”

The mission of the McKnight Foundation’s Technological Innovations in Neuroscience Award, as described on its website, is “to bring science closer to the day when diseases of the brain and behavior can be accurately diagnosed, prevented and treated.”

Related:
Singing in the brain: Songbirds sing like humans
Dopamine key to vocal learning, songbird study finds

Science on stage: Atlanta playwrights explore the human microbiome

Learning about the microbiome "is shifting my perspective of what it means to be human and an individual," says playwright Margaret Baldwin. "What bacteria are driving our dreams?"

Four Atlanta playwrights + 48 hours = four new plays at the forefront of art and science.

That’s the premise of Theater Emory’s “ 4:48,” a frenetic yet focused showcase of new works inspired by the human microbiome that will be performed July 14 at the Schwartz Center for Performing Arts.

The annual speed-writing challenge always yields compelling results, as talented local playwrights come together at Emory to quickly produce plays based on common source material. But this year, for the first time, the Playwriting Center of Theater Emory is teaming up with the Emory Center for the Study of Human Health for “4:48” — an innovative, interdisciplinary collaboration that promises to push the boundaries of both fields.

“Theater offers an exciting communication mechanism to convey cutting edge-research findings to a wide audience, while simultaneously encouraging curiosity and imagination,” says Amanda Freeman, instructor in the Center for the Study of Human Health.

The collaborators hope that this project will introduce the human microbiome — the trillions of microorganisms that live in us and on us — to a whole new audience, providing a spotlight for research that is being done right here on campus.

“I have found very few venues where new science and new art can emerge from a single exercise, so ‘4:48’ is special,” says David Lynn, Asa Griggs Candler Professor of Chemistry and Biology, one of several Emory science faculty offering support as resources for the writers.

Readings of the work developed during "4:48" begin at 4 pm on Saturday, July 14, in the Theater Lab of Schwartz Center. All readings are free and open to the public. For the schedule of readings and play titles, visit the Theater Emory website.

Click here to learn more.

Related:
Learning to love our bugs: Meet the microorganisms that help keep us healthy
Environment, the microbiome and preterm birth

New Atlanta NMR Consortium links resources of Emory, Georgia Tech and Georgia State

The Atlanta Nuclear Magnetic Resonance Consortium "lowers the activation energy to take advantage of partners’ expertise," says Emory chemist David Lynn.


NMR – nuclear magnetic resonance – is a powerful tool to investigate matter. It is based on measuring the interaction between the nuclei of atoms in molecules in the presence of an external magnetic field; the higher the field strength, the more sensitive the instrument.

For example, high magnetic fields enable measurement of analytes at low concentrations, such as the compounds in the urine of blue crabs, opening doors to understanding how chemicals invisibly regulate marine life. High-field NMR also allows scientists to “see” the structure and dynamics of complex molecules, such as proteins, nucleic acids, and their complexes.

NMR is used widely in many fields, from biochemistry, biology, chemistry, and physics, to geology, engineering, pharmaceutical sciences, medicine, food science, and many others.

David Lynn

NMR instruments, however, are a major investment. The most advanced units can cost up to up to millions of dollars per piece. Maintenance can cost tens of thousands of dollars a year. The investment in people is also significant. It can take years of training before a user can perform some of the most advanced techniques.

For these and other reasons, Emory University, Georgia Institute of Technology, and Georgia State University have formed the Atlanta NMR Consortium. The aim is to maximize use of institutional NMR equipment by sharing facilities and expertise with consortium partners.

Through the consortium, students, faculty, and staff of a consortium member can use the NMR facilities of their partners. The cost to a consortium member is the same as what the facility charges its own constituents.

“NMR continues to grow and develop because of technological advances,” says David Lynn, a chemistry professor at Emory University. To keep up, institutions need to keep buying new, improved instruments. Such a never-ending commitment is becoming untenable and redundant across Atlanta, Lynn says. Combining forces is the way to go.

Immediately, the consortium offers access to the most sensitive instruments now in Atlanta – the 700- and 800-MHz units at Georgia Tech. Georgia Tech invested more than $5 million to install the two high-field units, as well as special capabilities, in 2016.

Partners can gain access to Georgia State’s large variety of NMR probes. Solid-state capability, which is well established in Emory and advancing at Georgia Tech, will be available to partners.

Needless to say, the consortium offers alternatives when an instrument at a member institution malfunctions.

Beyond maximizing use of facilities, the consortium offers other potential benefits.

Anant Paravastu

“The biggest benefit is community,” says Anant Paravastu. Paravastu is an associate professor in the Georgia Tech School of Chemical and Biomolecular Engineering. He is also a member of the Parker H. Petit Institute for Bioengineering and Bioscience (IBB).

“Each of us specializes the hardware and software for our experiments,” Paravastu says. “As we go in different directions, we will benefit from a cohesive community of people who know how to use NMR for a wide range of problems.”

Paravastu previously worked at the National High Magnetic Field Laboratory, in Florida State University. That national facility sustains a large community of NMR researchers who help each other build expertise, he says. “We Atlanta researchers would benefit from a similar community, and not only for the scientific advantage.”

Both Lynn and Paravastu believe the consortium will help the partners jointly compete for federal grants for instrumentation. “A large user group will make us more competitive,” Lynn says. “The federal government would much rather pay for an instrument that will benefit many scientists rather than just one research group in one university,” Paravastu says.

“The most important goal for us is the sharing of our expertise,” says Markus Germann, a professor of chemistry at Georgia State. A particular expertise there is the study of nucleic acids. More broadly, Georgia State has wide experience in solution NMR. Researchers there have developed NMR applications to study complex structures of biological and clinical importance.

Germann offers some examples:
Structure and dynamics of damaged and unusual DNA
Structure and dynamics of protein—DNA and protein—RNA complexes
Structural integrity of protein mutants
Small ligand-DNA and -RNA binding for gene control
Protein-based contrast agents for magnetic resonance imaging

“For me, there’s a direct benefit in learning from people at Georgia State about soluble-protein structure,” Paravastu says. He studies the structures of peptides; of particular interest are certain water-soluble states of beta-amyloid peptide, in Alzheimer’s disease. These forms, Paravastu says, have special toxicity to neurons.

Markus Germann

Paravastu also studies proteins that self-assemble. “People at Emory have a different approach to studying self-assembling proteins,” he says. “We have a lot of incentive to strengthen our relationships with other groups.”

“Different labs do different things and have different expertise,” Lynn says. “The consortium lowers the activation energy to take advantage of partners’ expertise.”

Even before the consortium, Germann notes, his lab has worked with Georgia Tech’s Francesca Storici on studies of the impact of ribonucleotides on DNA structure and properties. Storici is a professor in the School of Biological Sciences and a member of IBB.

Germann has also worked with Georgia Tech’s Nicholas Hud on the binding of small molecules to duplex DNA. Hud is a professor in the School of Chemistry and Biochemistry and a member of IBB.

“While collaborations between researchers in Atlanta universities is not new,” Paravastu says, “the consortium will help facilitate ongoing and new collaborations."

What will now be tested is whether the students, faculty, and staff of the partners will take advantage of the consortium.

Travel from one institution to another is a barrier, Lynn says. “Are people going to travel, or will they find another way to solve the problem? How do you know that the expertise over there will really help you?” he asks.

“The intellectual barrier is very critical,” Lynn says. “We address that through the web portal.”

The website defines the capabilities, terms of use, training for access, and institutional fees, among others. Eventually, Lynn says, it will be a place to share papers from the consortium partners.

“Like many things in life, the consortium is about breaking barriers,” Paravastu says. It’s about students meeting and working with students and professors outside their home institutions.

Already some partners share a graduate-level NMR course. For the long-term, Paravastu suggests, the partners could work together on training users to harmonize best practices and ease the certification to gain access to facilities.

“We can think of students being trained by the consortium rather than just by Georgia Tech, or Emory, or Georgia State,” Paravastu says. “By teaming up, we can create things that are bigger than the sum of the parts.”

Written by by Maureen Rouhi, Georgia Tech

Related:
How protein misfolding may kickstart chemical evolution
Peptides may hold 'missing link' to life

Study reveals how the brain decides to make an effort

"Understanding how the brain works normally when deciding to expend effort provides a way to pinpoint what's going on in disorders where motivation is reduced," says Emory psychologist Michael Treadway, whose lab conducted the study.

By Carol Clark

From deciding to quit hitting the snooze button and get out of bed in the morning to opting to switch off the TV and prepare for sleep at night, the mind weighs the costs versus benefits of each choice we make. A new study reveals the mechanics of how the brain makes such effortful decisions, calculating whether it is worth expending effort in exchange for potential rewards.

The Proceedings of the National Academy of Sciences (PNAS) published the findings by psychologists at Emory University.

“We showed that the brain’s ventromedial prefrontal cortex, which was not previously thought to play a key role in effort-based choices, actually appears to be strongly involved in the formation of expectations underlying those choices,” says Emory psychologist Michael Treadway, senior author of the paper.

Treadway’s lab focuses on understanding the molecular and circuit-level mechanisms of psychiatric symptoms related to mood, anxiety and decision-making.

“Understanding how the brain works normally when deciding to expend effort provides a way to pinpoint what’s going on in disorders where motivation is reduced, such as depression and schizophrenia,” he says.

Previous research had observed three brain regions in decision-making; the dorsal anterior cingulate cortex (dACC), the anterior insula (aI) and the ventromedial prefrontal cortex (vmPFC). Studies had pointed to the vmPFC as central to the computation of subjective value during probability decision-making. But prior evidence also suggested that when it comes to decisions about effort expenditure, those subjective value estimates were not computed by the vmPFC but by the other two brain regions.

A limitation to previous studies on effort-based choices is that they simultaneously presented the costs and benefits of a choice to experimental subjects.

“In the real world, however, we usually have to make decisions based on incomplete information,” says Amanda Arulpragasam, first author of the PNAS paper and a psychology PhD candidate in Treadway’s lab.

Arulpragasam designed a study that allowed the researchers to model distinct neural computations for effort and reward.

Subjects underwent functional magnetic resonance imaging (fMRI) while performing an effort-based decision-making task where the effort costs and rewards of a choice were presented separately over time.

The subjects could choose to make no effort and receive $1, or make some level of physical effort in exchange for monetary rewards of varying magnitude, up to $5.73. The physical effort involved rapid button pressing at varying percentages of each participant’s maximum button pressing rate. Participants were required to press the button using their non-dominant pinkie finger, making the task challenging enough to be unpleasant, although not painful.

In the effort-first trials, participants were shown a vertical bar representing the percentage of their maximum button pressing rate that would be required to do the task. They were then shown the size of the reward for performing the task. The reward-first trials presented the information in the opposite order.

After receiving both sets of information, participants were prompted to choose the no-effort option or the effort option.

The experimental design allowed the researchers to tease apart the effects of recent choices on the formation of value expectations of future decisions.

The results revealed a clear role for the vmPFC in encoding an expected reward before all information had been revealed. The data also suggested that the dACC and aI are involved in encoding the difference between what participants were expecting and what they actually got, rather than effort-cost encoding.

“Some have argued that decisions about effort have a different neural circuitry than decisions about probability and risk,” Treadway says. “We’ve showed that all three brain regions come into play, just in a different way than was previously known.”

Co-authors of the PNAS paper include Jessica Cooper, a post-doctoral fellow in the Treadway lab and Makiah Nuutinen, a research interviewer in the lab.

Related:
Twitter reveals how future-thinking Americans are and how that affects their decisions

Dengue 'hot spots' provide map to chikungunya and Zika outbreaks

A street scene in Merida, Mexico, a city of about one million in the Yucatan Peninsula where the study was based. Merida had a little over 40,000 reported dengue cases during 2008 to 2015 and nearly half of them were clustered in 27 percent of the city.

By Carol Clark

Identifying dengue fever “hot spots” can provide a predictive map for outbreaks of chikungunya and Zika — two other viral diseases that, along with dengue, are spread by the Aedes aegypti mosquito.

PLOS Neglected Tropical Diseases published the findings, the first confirmation of the spatial-temporal overlap for outbreaks of the three diseases, led by Emory University.

“We had hypothesized that we would see some overlap between these diseases, but we were surprised at the strength of that overlap,” says Gonzalo Vazquez-Prokopec, a disease ecologist in Emory’s Department of Environmental Sciences and lead author of the study. “The results open a window for public health officials to do targeted, proactive interventions for emerging Aedes-borne diseases. We’ve provided them with a statistical framework in the form of a map to guide their actions.”

The analysis drew from eight years of data from Merida, Mexico, on symptomatic cases. A city of one million located in the Yucatan Peninsula, Merida had about 40,000 reported dengue cases during 2008 to 2015, and nearly half of them were clustered in 27 percent of the city. The neighborhoods comprising these dengue hot spots contained 75 percent of the first chikungunya cases reported during the outbreak of that disease in 2015 and 100 percent of the first Zika cases reported during the Zika outbreak in 2016.

“Currently, most mosquito control efforts are not done until cases of mosquito-borne diseases are detected,” Vazquez-Prokopec says. “But by the time you detect a virus in an area, it has likely already begun to spread beyond that area.”

Mosquito control efforts generally involve outdoor spraying that covers broad swaths of a city, further reducing efficacy, he adds. Outdoor spraying is particularly ineffective for the Aedes aegypti mosquito. “This mosquito is highly adapted to urban environments,” Vazquez-Prokopec says. “It likes to live inside houses and to feed on people.”

A targeted approach would make it more feasible to implement time-consuming and costly interventions such as indoor residual spraying.

A technician sprays the ceiling and walls of a home in Merida. Indoor residual spraying is effective, but is not practical for large areas of a city, due to the time and expense involved. Photo by Nsa Dada.

“The statistical framework that we have developed allows public health officials to harness the power of big data to do more effective and efficient mosquito control by focusing on high-risk areas — even before an epidemic begins,” Vazquez-Prokopec says.

The study used disease case reports at the household level and then scaled them up to neighborhoods to protect individuals’ privacy in the final map. The hot spots for reported dengue cases were confirmed by data from laboratory blood tests of a cohort of 5,000 people. The analysis showed that people living in a dengue hot spot had twice the rate of infection of those outside of the hot spots.

The research team included scientists from the Autonomous University of Yucatan and health officials from the state and federal level in Mexico. Other members of the team were scientists from seven other universities and health research institutions, including the U.S. Centers for Disease Control and Prevention.

The researchers are now working with the Pan American Health Organization (PAHO) to develop a manual and training materials, based on open-access software, for mapping risks of Aedes-borne diseases to guide proactive interventions throughout urban areas of the developing world.

More than one third of the world’s population lives in areas at high risk for infection with the dengue virus, a leading cause of illness and death in the tropics and subtropics, according to the Centers for Disease Control and Prevention. Dengue fever is sometimes called “break bone fever” due to the excruciating pain that is among its symptoms.

The chikungunya virus emerged in the Americas in 2013, sweeping through many countries where dengue is endemic. Common symptoms of chikungunya infection may include headache, muscle pain, joint swelling and rash.

Zika virus followed in 2016, causing little alarm at first due to its relatively mild symptoms. It soon became apparent, however, that the Zika virus could cause birth defects in the babies of pregnant women who were infected.

“You tend to see transmission go down right after large numbers of a population are infected with these Aedes-borne viruses, leading to herd immunity,” Vazquez-Prokopec says. “But these viruses do not disappear. They keep circulating and can reappear later.”

Meanwhile, new Aedes-borne viruses are likely to emerge, he adds, as rapid urbanization and a warming climate help the mosquito thrive.

Vaccines are not yet available for chikungunya or Zika, and efforts to roll out a vaccine for dengue are complicated by the fact that the virus comes in different serotypes.

“Although effective vaccines would be the ultimate line of defense against these diseases, we cannot give up on mosquito control,” Vazquez-Prokopec says.

Related:
Contact tracing, with indoor spraying, can curb dengue outbreak
Zeroing in on 'super spreaders' and other hidden patterns of epidemics
Human mobility data may help curb epidemics

Science Art Wonder: Students team with labs to bring research to life

Art by Emory senior Pamela Romero, Science.Art.Wonder. founder and president, portrays how aphids can develop wings in response to environmental changes. The DNA painted along the edges of the canvases is the same, except that different genes are switched on. Photo by Ann Watson, Emory Photo/Video

By Carol Clark

A small crowd gathers in Emory’s White Hall before the menacing sight: Large rubber worms arrayed on triangular red spikes. The jagged spikes, from a few inches to more than a foot tall, lean crazily in all directions. Some of the worms — suspended on near-invisible fishing line — appear to rise off the spikes, escaping to a circular mirror hanging from above.

“This is how evolution works!” says Ethan Mock, a sophomore majoring in ancient history, who created the sculpture, titled "The Crucible." He looks dapper in a leather vest and tweed cap and speaks with theatrical flair to the crowd. “The spikes represent the trials and tribulations of the worms’ struggles. Most are trapped in the spikes but a few climb out, not realizing that they are simply climbing into a new trial, a new test.”

The onlookers include a mix of college students, children and their parents, brought together by campus events during the recent Atlanta Science Festival. Joining the regular attractions of Physics Live! and Chemistry Carnival is the debut of an art exhibit by a new, student-run program called Science.Art.Wonder., or S.A.W. Just over 100 artists — most of them untrained college students — teamed with scientists from Emory and Georgia Tech to translate their research into art.

Ethan Mock and his art, "The Crucible"

Mock worked with the lab of Levi Morran, an assistant professor in Emory’s Department of Biology who studies co-evolutionary dynamics by experimenting with a host (a microscopic worm called C. elegans) and a parasite (a bright red species of bacteria called Serratia marcescens that is lethal to C. elegans upon consumption).

“This is so cool!” says Pareena Sharma, a first-year biochemistry major at Emory, as she snaps a photo of the sculpture. “It’s so relatable to me. I’ve been doing this same experiment since the first of the semester in Biology 142.”

Two young boys draw near the spikes. “Look up into the mirror,” Mock encourages them. “Now tell me what you see.”

“The same thing,” one of the boys replies.

“That’s right!” Mock says. “The process of evolution keeps repeating, going in a loop.”

Morran, arriving with his eight-year-old daughter, Maggie, is impressed. “You could see the light come on in those boys’ eyes,” he says. “They understood what Ethan is trying to convey. And it’s not an easy concept to grasp — the continual evolutionary struggle.”

Both artists and researchers engage with visitors as they peruse more than 140 works of art, set up on the Quad, in White Hall, the Math and Science Center and the Atwood Chemistry Center during the festival.

“This artwork gives you a snapshot of how much research is being done in Atlanta. I’m taken aback by how cutting edge and varied it is,” says Pamela Romero, president of S.A.W. The program is the brainchild of Romero, a senior majoring in neuroscience and behavioral biology and minoring in computer science.

Young visitors to the Emory campus peruse science-inspired art on the Quad. Photo by Ann Watson, Emory Photo/Video

The Emory S.A.W. contributions span labs across the University and beyond. The artists picked their mediums, from acrylic to watercolor and everything in between.

Emily Isaac, a first-year Emory student majoring in environmental sciences and theater, stands on the Quad next to a large watercolor she painted. “Art can help scientists make a point without using any scientific jargon,” she says.

She teamed with Robert Wallace from Georgia Tech’s Agricultural Technology Research Program. One of Wallace’s projects gave plots of farmland to women in India who had been victims of an acid attack. Isaac did a portrait of a woman with a scarred face. The woman’s head is partially wrapped in strips of bandages that Isaac painted to look like rows of newly sprouting plants. “I wanted to show hope, and how connecting with the environment can help people,” Isaac says.

This year’s 36 Emory S.A.W. artists are mainly undergraduates — many of them science majors — but they also include a few graduate students, faculty and staff members. Georgia Tech makes up the bulk of other contributing artists and researchers in this year’s S.A.W., although 10 independent artists also got involved, along with Georgia State University undergraduates and the Atlanta campus of SCAD.

“S.A.W. is collaborative, not only across disciplines and institutions, but also across students, faculty, staff and members of the Atlanta community,” Romero says. “We even have one international artist, from Puerto Rico.”

A painting by Georgia Tech student Bianca Guerrero portrays a virtual reality game used to measure players' perception of time as well as eye movement. The art is based on research by Georgia Tech psychologist Malia Crane. Photo by Ann Watson, Emory Photo/Video.

As long as she can remember, everyone thought Romero would become an artist, or maybe an architect. She began taking art classes at the age of three in her home town of Tegucigalpa, Honduras. She continued making and studying art, developing a surrealist style.

In ninth grade, however, a psychology course sparked a fascination for neurobiology. Romero took online classes and started reading up on subjects like optogenetics and deep-brain stimulation.

By the time she was accepted to Emory, she had decided to forge a career as a scientist. “A lot of people told me that if I chose neuroscience I would have to forsake art, because I would be a bad scientist if I tried to do both,” she recalls. “I was determined to prove them wrong.”

Romero sought out kindred spirits like Nicole Gerardo, associate professor of biology, who also grew up with twin passions for science and art. Gerardo once had students create artwork using microbes in her lab under the direction of Nancy Lowe — a former lab technician at Emory who went on to create a retreat center in North Carolina called AS.IF: Art and Science in the Field.

Gerardo later paired students with labs to create ceramic representations of research under the direction of Diane Kempler, who formerly taught visual arts at Emory.

“Art provides a way to reach people who may be intimidated by science,” Gerardo says. “And working with an artist lets scientists see their own work in a different way. That could lead to new scientific approaches.”

When Romero first joined forces with Gerardo it was simply to produce art for her lab, which focuses on evolutionary ecology. “We were test subjects for S.A.W.,” Romero says.

Emory senior Maureen Ascona, a neuroscience and behavioral biology major, discusses her art with visitors to the Quad. Ascona teamed with Helen Mayberg, from the Emory School of Medicine, who uses deep-brain stimulation to help patients with treatment-resistant depression. Photo by Ann Watson, Emory Photo/Video.

One of the pieces Romero created consists of triangular canvases that can be shifted into different positions. The acrylic painting depicts how aphids develop wings in the presence of predators, like ladybugs, or if food becomes scarce. “When Dr. Gerardo explains her work to people, she can move the canvases to show how the aphids change in response to their environment,” Romero says.

Romero wanted to give other students the chance to enter research labs and experiment with art.

“Pamela is an amazing woman, a force of nature,” says Gerardo, who is the faculty mentor for S.A.W. “What she has done with the support of her fellow students is incredible. I had envisioned maybe 20 pairings of scientists and artists. I’m still surprised by how big it became.”

Connections from across the University helped S.A.W. grow. Wei Wei Chen and John Wang, student leaders of Emory Arts Underground, provided the platform for Romero to launch S.A.W. and encouraged her to form a charter, bylaws and an executive team. That team includes Emory undergraduates Alex Nazzari (vice-president), Aila Jiang, Veronica Paltaraskaya, Anne Pizzini, Deborah Seong and John Wang, along with Georgia Tech students Olivia Cox, Siyan Li and Iris Liu.

The students’ efforts paid off with S.A.W.’s smash debut at the Atlanta Science Festival.

“One of my favorite parts was guiding artists through the process of disentangling the science, reassuring them that they could do it,” Romero says. “Many of them felt overwhelmed after first talking to a scientist. Some of them were first-year students who hadn’t even had introductory biology or chemistry.”

A piece by Alice Yang, a first-year Emory student majoring in neuroscience and behavioral biology who teamed with researchers of human genetics in the Emory 3q29 Project. Photo courtesy of S.A.W.

Exploring a lab through an art project allows students to develop a relationship with a researcher and often find a mentor, Romero says.

Alice Yang, a first-year Emory student majoring in neuroscience and behavioral biology, teamed with Jennifer Mulle, assistant professor at Rollins School of Public Health. Mulle is co-principal investigator of the Emory 3q29 Project, which seeks to understand a genetic deletion associated with an increased risk for schizophrenia.

“I’m so grateful for the experience,” Yang says of spending time with the 3q29 Project team. “I learned what it’s like to actually do science. And I caught their passion. People are just now realizing how genetics can be involved in mental illness. It’s a very new field.”

To create her art pieces, Yang ordered special scratch-off paper from her native China. “This paper’s easy to work with and it’s great for showing patterns and textures,” she says. She explains how she carefully cut slices from the black top layer of the paper to reveal the glowing, rainbow colors beneath. Her pictures portray the nanomapping of fluorescent-labeled alleles from the 3q29 lab while also paying tribute to Salvador Dali’s surrealism.

Even those who are not aspiring scientists can catch the science-art bug. Independent artist Aaron Artrip teamed with scientists Matthew Jackson and Dan Cook at Georgia Tech to demonstrate interaction with sound. A group of children buzzes around Artrip’s exhibit in White Hall. A piece of paper sprinkled with powdered black ink is taped to a wooden speaker, which is plugged into an electronic synthesizer. As Artrip taps a keyboard, the powder moves across the page, creating patterns.

“I’m making drawings with vibrations. Forcing sound through the ink causes it to move,” he explains.

“Would you like to try?” he asks a young girl watching him.

She doesn’t have to be asked twice.

A painting by Georgia Tech student Kate Bernart, "Connecting the Cycle," portrays Austin Ladshaw's research at Georgia Tech's School of Environmental Engineering on the nuclear fuel cycle and ways to prevent excessive accumulations of radioactive waste. Photo by Ann Watson, Emory Photo/Video

Ultimately, S.A.W. hopes to find ways to integrate its art-science model into grades K-12. “We would like to have artists and researchers go into K-12 classrooms to talk about the art and the research together,” Romero says.

She presented S.A.W. at the recent Georgia Tech STEAM Leadership Conference, which brought together educators and policymakers to explore new ways to teach science, technology, engineering, art and math, or STEAM. S.A.W. is now working to put together an anthology of its art into a booklet, to include descriptions of the science. The booklet will be aimed at high school students “to give them a glimpse of some of the possible fields available to them in college,” Romero says.

S.A.W. is also creating a web site where the art will be accessible in digital form, including videos of some of the interactive art pieces, along with other resources for K-12 teachers.

After graduating this spring, Romero plans to take a gap year, then go on to graduate school with the aim of becoming a professor with a research lab. “S.A.W. has an incredible executive team and I’m making sure that the program continues after I leave Emory,” she says. “I would also like to stay involved with it in some way.”

As she prepares for graduation, Romero is working on an art narrative piece funded by the Emory Center for Creativity and Arts. The work will combine acrylic painting and sculpture to represent the element Vanadium, discovered by Mexican mineralogist Andrews Manuel del Rio in 1801. A series of circular canvases will each represent an atom in Vanadium. Each canvas will also represent a country or group of countries in Latin America, on which Romero will depict the research of a scientist from that area.

“My main goal with this piece is to celebrate and encourage more Latin American science,” Romero says. She is calling the piece “Elementally Latino,” to describe how Latinos are an elemental, or basic, part of science and how they also embody an elemental force. “Latinos are such a passionate people that I can only adequately describe them as a force of nature,” she says.

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Biologists unravel another mystery of what makes DNA go 'loopy'

Interior of a cell showing the nucleus with the chromatin fiber (yellow) arranged in the three-dimensional space by loops formed by the CTCF protein (shown in pink). DNA is represented by thin blue lines on the chromatin. Graphic by Victor Corces. 

By Carol Clark

Scientists discovered another key to how DNA forms loops and wraps inside the cell nucleus — a precise method of “packing” that may affect gene expression.

The journal Science published the research by biologists at Emory University, showing that a process known as hemimethylation plays a role in looping DNA in a specific way. The researchers also demonstrated that hemimethylation is maintained deliberately — not through random mistakes as previously thought — and is passed down through human cell generations.

“In order for a protein called CTCF to make loops in the DNA, we discovered that it needs to have hemimethylated DNA close by,” says Emory biologist Victor Corces, whose lab did the research. “Nobody had previously seen that hemimethylated DNA has a function.”

Chenhuan Xu, a post-doctoral fellow in the Corces lab, developed experimental methods for DNA methylome mapping to conduct the research for the Science paper.

Chromatin is made up of CTCF and other proteins, along with DNA and RNA. One role of chromatin is to fold and package DNA into more compact shapes. Growing evidence suggests that this folding process is not just important to fit DNA into a cell nucleus — it also plays a role in whether genes are expressed normally or malfunction.

The Corces lab specializes in epigenetics: The study of heritable changes in gene function — including chromatin folding — that do not involve changes in the DNA sequence.

DNA methylation, for example, can modify the activity of DNA by adding methyl groups to both strands of the double helix at the site of particular base pairs. The process can be reversed through demethylation.

As cells divide they make a copy of their DNA. In order to do so, they have to untangle the two strands of DNA and split them apart. Each parental strand then replicates a daughter strand.

“When cells divide, it’s important that they keep the methylation the same for both strands,” Corces says, noting that altered patterns of methylation are associated with cancer and other diseases.

Hemimethylation involves the addition of a methyl group to one strand of the DNA helix but not the other. Some researchers observing hemimethylation have hypothesized that they were catching it right after cell division, before the cell had time to fully replicate to form a daughter strand. Another theory was that hemimethylation was the result of random mistakes in the methylation process.

The methods developed by Xu in the Corces lab allowed the researchers to observe hemimethylation on DNA in human cells in real-time before, during and after cell division. They also mapped it as the cells continued to replicate.

“If the parental DNA was hemimethylated, the daughter DNA was also hemimethylated at the same place in the genome,” Corces says. “The process is not random and it’s maintained from one cell generation to the next over weeks.”

The researchers found that hemimethlyation only occurs near the binding sites of CTCF — the main protein involved in organizing DNA into loops.

“If we got rid of the hemimethlyation, CTCF did not make loops,” Corces says. “Somehow, hemimethylation is allowing CTCF to make loops.”

And when CTCF makes a loop, it does so by binding ahead, going forward in the DNA sequence, they observed.

“Research suggests that some disorders are associated with CTCF binding — either mutations in the protein itself or with the DNA sequence where the protein binds,” Corces says. “It comes back to the story of how important these loops are to the three-dimensional organization of chromatin, and how that organization affects the gene expression.”

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Biophysicists discover how small populations of bacteria survive treatment

"We showed that by tuning the growth and death rate of bacterial cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations," says biophysicist Minsu Kim. His lab conducted experiments with E. coli bacteria (above).

By Carol Clark

Small populations of pathogenic bacteria may be harder to kill off than larger populations because they respond differently to antibiotics, a new study by Emory University finds.

The journal eLife published the research, showing that a population of bacteria containing 100 cells or less responds to antibiotics randomly — not homogeneously like a larger population.

“We’ve shown that there may be nothing special about bacterial cells that aren’t killed by drug therapy — they survive by random chance,” says senior author Minsu Kim, an assistant professor in the Department of Physics and a member of Emory’s Antibiotic Resistance Center.

“This randomness is a double-edged sword,” Kim adds. “On the surface, it makes it more difficult to predict a treatment outcome. But we found a way to manipulate this inherent randomness in a way that clears a small population of bacteria with 100 percent probability. By tuning the growth and death rate of bacterial cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations.”

Jessica Coates, as a graduate student at Emory, and Bo Ryoung Park, a research associate in the Kim lab, are co-first authors of the paper. Additional authors are graduate student Emrah Simsek and post-doctoral fellows Dai Le and Waqas Chaudry.

The researchers developed a treatment model using a cocktail of two different classes of antibiotic drugs. They first demonstrated the effectiveness of the model in laboratory experiments on a small population of E. coli bacteria without antibiotic-drug resistance. In later experiments, they found that the model also worked on a small population of clinically-isolated antibiotic-resistant E. coli.

“We hope that our model can help in the development of more sophisticated antibiotic drug protocols — making them more effective at lower doses for some infections,” Kim says. “It’s important because if you treat a bacterial infection and fail to kill it entirely, that can contribute to antibiotic resistance.”

Antibiotic resistance is projected to lead to 300 million premature deaths annually and a global healthcare burden of $100 trillion by 2050, according to the 2014 Review on Antimicrobial Resistance. The epidemic is partly driven by the inability to reliably eradicate infections of antibiotic-susceptible bacteria.

For decades, it was thought that simply reducing the population size of the bacteria to a few hundred cells would be sufficient because the immune system of an infected person can clear out the remaining bacteria.

“More recently, it became clear that small populations of bacteria really matter in the course of an infection,” Kim says. “The infectious dose — the number of bacterial cells needed to initiate an infection — turned out to be a few or tens of cells for some species of bacteria and, for others, as low as one cell.”

It was not well understood, however, why treatment of bacteria with antibiotics sometimes worked and sometimes failed. Contributing factors may include variations in the immune responses of infected people and possible mutations of bacterial cells to become more virulent.

Kim suspected that something more fundamental was a factor. Research has shown unexpected treatment failure for antibiotic-susceptible infections even in a simple organism like the C. celegans worm, a common model for the study of bacterial virulence.

By focusing on small bacteria populations, the Emory team discovered how the dynamics were different from large ones. Antibiotics induce the concentrations of bacterial cells to fluctuate. When the growth rate topped the death rate by random chance, clearance of the bacteria failed.

The researchers used this knowledge to develop a low-dose cocktail drug therapy of two different kinds of antibiotics. They combined a bactericide (which kills bacteria) and a bacteriostat (which slows the growth of bacteria) to manipulate the random fluctuation in the number of cells and boost the probability of the cell death rate topping the growth rate.

Not all antibiotics fit the model and more research is needed to refine the method for applications in a clinical setting.

 “We showed that the successful treatment of a bacterial infection with antibiotics is even more complicated than we thought,” Kim says. “We hope this knowledge leads to new strategies to fight against infections caused by antibiotic-resistant bacteria.”

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Ecosystems hanging by a thread

Emory disease ecologist Thomas Gillespie served on an international committee that developed best practice guidelines for health monitoring and disease control in great ape populations, part of a growing public education effort.

By Tony Rehagen
Emory Magazine

Thomas Gillespie’s parents and teachers always wanted him to go into medicine.

“Growing up in Rockford, Illinois, if you were smart and interested in biology, you were supposed to be a doctor,” he says.

Gillespie, meanwhile, was always more interested in primates. In seventh grade, he phoned animal psychologist Penny Patterson, famous for teaching the gorilla Koko how to use sign language, and interviewed the scientist about Koko’s diet while punching out notes on a typewriter. He was premed at the University of Illinois, but spent his internship at the Brookfield Zoo in Chicago, working in the “Tropic World” primate exhibit. His favorite undergrad course was biological anthropology, the study of biological and behavioral aspects of humans and nonhuman primates, looking at our closest relatives to better understand ourselves.

Gillespie eventually took a year off before graduate school to work with primate communities in the Peruvian Amazon. The apes finally won out — Gillespie would choose a doctorate in zoology over medical school.

But it wasn’t long before the two fields of study collided. While monitoring the group behavior of colobine monkeys in Africa, Gillespie observed that some of the animals were eating bark from the African cherry tree — not a typical food source for them. When he dug deeper, Gillespie learned that human doctors in the region used that same bark to treat parasites in their patients. The monkeys, he realized, were self-medicating.

“That discovery in these monkeys brought me back toward the health science side of biology,” says Gillespie.

Gillespie’s return to a medical approach to zoology came not a moment too soon—for the sake of the primates and maybe even all of humankind. As an associate professor in Emory’s Department of Environmental Sciences specializing in the disease ecology of primates, Gillespie and his team of researchers have helped uncover a crisis among our nearest taxonomic neighbors. According to an article coauthored by Gillespie and thirty other experts and published in the journal Science Advances, 75 percent of the world’s five-hundred-plus primate species are declining in population, and a whopping 60 percent face extinction, largely due to human encroachment.

Read more in Emory Magazine.

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New method calculates equilibrium constant at the small scale

Mixing computational chemistry and theoretical math proved a winning formula for Emory chemist James Kindt (center), his graduate students (from left) Xiaokun Zhang and Lara Patel, and mathematics graduate students Olivia Beckwith and Robert Schneider. Photo by Stephen Nowland, Emory Photo/Video.

By Carol Clark

Computational chemists and mathematicians have developed a new, fast method to calculate equilibrium constants using small-scale simulations — even when the Law of Mass Action does not apply.

The Journal of Chemical Theory and Computation published the resulting algorithm and software, which the researchers have named PEACH — an acronym for “partition-enabled analysis of cluster histograms” and a nod to the method’s development in Georgia at Emory University.

“Our method will allow computational chemists to make better predictions in simulations for a wide range of complex reactions — from how aerosols form in the atmosphere to how proteins come together to form amyloid filaments implicated in Alzheimer’s disease,” says James Kindt, an Emory professor of computational chemistry, whose lab led the work.

Previously it would require at least a week of computing time to do the calculations needed for such predictions. The PEACH system reduces that time to seconds by using tricks derived from number theory.

“Our tool can use a small set of data and then extrapolate the results to a large-system case to predict the big picture,” Kindt says.

“What made this project so fun and interesting is the cross-cultural aspects of it,” he adds. “Computational chemists and theoretical mathematicians use different languages and don’t often speak to one another. By working together we’ve happened onto something that appears to be on the frontiers of both fields.”

The research team includes Lara Patel and Xiaokun Zhang, who are both PhD students of chemistry in the Kindt lab, and number theorists Olivia Beckwith and Robert Schneider, Emory PhD candidates in the Department of Mathematics and Computer Science. Chris Weeden, as an Emory undergraduate, contributed to early stages of the work.

The equilibrium constant is a basic concept taught in first-year college chemistry. According to the Law of Mass Action, at a given temperature, no matter how much of a product and a reactant are mixed together — as long as they are at equilibrium — a certain ratio of product to reactant will equal the equilibrium constant.

“That equation always holds true at equilibrium for huge numbers of molecules,” Kindt says. “It doesn’t matter if it’s applied to a bucket of water or to a single drop of water — which consists of about a billion trillion molecules.”

At much smaller scales of around dozens of molecules, however, the Law of Mass Action breaks down and does not apply.

The Kindt lab uses computers to simulate the behavior of molecules, in particular how they self-assemble into clusters. Sodium octyl sulfate, or SOS, is one of the compounds the lab uses as an experimental model. SOS is a surfactant that can act as a detergent. It forms little clusters in water that can encapsulate oil and grease. Simulations of how SOS molecules come together can predict the distribution of sizes of clusters formed under different conditions, in order to improve the design of soaps and detergents, and to better understand biological processes such as how bile salts break down globules of fat during the digestive process.

In a key test of their model, the lab needed to make sure that the equilibrium for the assembly reaction of SOS molecules into clusters matched up with experiments.

“If we were to run simulations with huge numbers of molecules, we could count the clusters that were formed of each size, count the molecules that remained free of the clusters, and use this information to calculate the equilibrium constant for forming each size cluster,” Kindt says. “The challenge we faced was that it would take too long for the computers to perform simulations of sufficiently huge numbers of molecules to get this to work, and for the numbers of clustering molecules we could practically handle — around 50 — the Law of Mass Action wouldn’t work.”

Kindt decided to approach the problem by considering all the different ways the molecules in a reaction could group into clusters of different sizes in order to arrive at an average. After doing some reading, he realized that these different ways of molecules grouping were what number theorists call integer partitions.

A partition of a number is a sequence of positive integers that add up to that number. For instance, there are five partitions of the number 4 (4 = 3+1 = 2+2 = 2+1+1 = 1+1+1+1). The partition numbers grow at an incredible rate. The amount of partitions for the number 10 is 42. For the number 100, the partitions explode to more than 190,000,000.

That same explosion of possibilities occurs for the ways that molecules can cluster.

Lara Patel and Xiaokun Zhang worked on a “brute force” method to get a computer to run through every single way to combine 10 molecules of one type with 10 molecules of another type. The problem was it took one computer working a couple of days to do a single analysis. And the computational time needed if just a few more molecules were added to the analysis went up exponentially.

The computational chemists had hit a wall.

Kindt reached out to Ken Ono, a world-renowned number theorist in Emory's Mathematics and Computer Science Department, to see if any of his graduate students would be interested in taking a crack at the problem.

Olivia Beckwith and Robert Schneider jumped at the chance.

“The Kindt lab’s computer simulations show that classical theorems from partition theory actually occur in nature, even for small numbers of molecules,” Schneider says. “It was surprising and felt very cosmic to me to learn that number theory determines real-world events.”

“It was definitely unexpected,” adds Beckwith. “In theoretical math we tend to work in isolation from physical phenomena like the interaction of molecules.”

The chemists and mathematicians began meeting regularly to discuss the problem and to learn one another’s terminology. “I had to pull out my son’s high school chemistry book and spend a weekend reading through it,” Schneider says.

“It happened so organically,” Patel says of the process of blending their two specialties. “Olivia and Robert would write equations on the board and as soon as a formula made sense to me I’d start thinking in my head, ‘How can we code this so that we can apply it?’”

The two mathematicians suggested a strategy that could make the problem much easier to calculate, based on a theorem known as Faà di Bruno’s Formula.

“It was surprising,” Zhang says, “because it was an idea that never would have occurred to me. They helped us get unstuck and to find a way to push our research forward.”

“They helped us find a shortcut so that we didn’t have to generate all the partitions for ways that the molecules could clump together,” Kindt adds. “Their algorithm is a much more elegant and simple way to find the entire average overall.”

Patel and Zhang used this new algorithm to put together a piece of software to analyze data from the computer simulations. The resulting system, PEACH, speeds up calculations that previously took two hours to just one second. After demonstrating how PEACH simplifies simulations of SOS assemblages, the research team is moving on to simulate this process for a range of other molecules.

“We’re interested in describing how molecular structures dictate assembly in any type of scenario, such as the early stages of crystal formation,” Kindt says. “We’re also working on quantifying just where the Law of Mass Action breaks down. We could then refine the PEACH strategy to make it even more efficient.”

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Chimpanzee studies highlight disease risk to all endangered wildlife

Famed primatologist Jane Goodall with Emory disease ecologist Thomas Gillespie, who is working with the Jane Goodall Institute to study the health of chimpanzees in Tanzania's Gombe National Park.

The American Journal of Primatology just published a special edition bringing together experts who have contributed to the understanding of chimpanzee health at Gombe National Park in Tanzania and beyond. Gombe is the site where Jane Goodall pioneered her behavioral research of chimpanzees. Goodall’s work at Gombe began in 1960, and continues today through the Jane Goodall Institute, making it the longest field study of any animal.

Thomas Gillespie, associate professor in Emory’s Department of Environmental Sciences, was a guest editor of the special journal edition, along with fellow scientists Dominic Travis and Elizabeth Lonsdorf. Gillespie works at the interface of biodiversity conservation and global health. Much of his research examines how and why anthropogenic influences within tropical forests alter disease dynamics and place wild primates, people and other animals in such ecosystems at increased risk of pathogen exchange.

Following is an interview with Gillespie about the special journal issue and why research on chimpanzee health is important.

What is the current status of chimpanzees?

Both the common chimpanzee and the bonobo, the two chimpanzee subspecies, are endangered. Chimpanzees are the most closely related species to humans and we see them declining precipitously due to habitat loss and poaching. Typical estimates for the chimpanzee population are in the hundreds of thousands. That’s far less than the number of people in Atlanta for the entire chimpanzee species spread across all of Africa. There is a real risk of chimpanzees going locally extinct in core parts of their habitat. Chimpanzee communities in West Africa, for instance, have very little habitat left. They’re often found living in scraps of habitat between villages.

How important is health to conservation? 

Wildlife health is a critical conservation issue, but that’s something that’s only recently been recognized. Wildlife populations already dealing with poaching and habitat loss are more vulnerable to being knocked out by disease. It becomes even more difficult when they are exposed to new pathogens, from humans or domesticated animals.

On top of that, primates are dealing with shifts in the dynamics of pathogens like Ebola. Ebola’s been around for a long time in natural systems but now we’re seeing big mortality events in wild chimpanzees and other apes. The Lowland Gorillas are actually listed as critically endangered due to Ebola.

How did you become involved with Gombe and the Jane Goodall Institute?

Fifteen years ago, as evidence mounted that disease was playing an important role in the population declines observed in Gombe chimpanzees in Tanzania, Dominic Travis and Elizabeth Lonsdorf developed a prospective health monitoring system. They began to collect specific behavioral data on signs of respiratory and gastrointestinal illnesses, combined with body condition scoring on a monthly basis for the chimpanzee communities at Gombe, that paralleled efforts by the Mountain Gorilla Veterinary Project in Rwanda and Uganda.

When I met Dom and Elizabeth at a workshop in Germany in 2004, I was six years into efforts to understand how logging and forest fragmentation in and around Kibale National Park, Uganda, affected disease dynamics in resident primates. My findings in Uganda highlighted that some forms of anthropogenic disturbance can alter the dynamics of natural pathogens in wildlife, such as a legacy of selective logging. It also revealed that other forms of disturbance, such as active forest fragmentation, can lead to opportunities for pathogens to jump between species, including the introduction of pathogens from people and domesticated animals to wild primates.

Dom and Elizabeth asked me to join their effort and expand the scope of their project to a One Health approach. I initiated diagnostic surveillance linked to geographical indicators of species overlap for Gombe’s chimpanzees and baboons, as well as the people and domesticated animals within the Greater Gombe Ecosystems. It serves as a map of all the places these species are interacting, for a greater sense of how transmission may be occurring. Integration of these new data streams, along with the ongoing observational health data and in-depth post-mortem necropsies, have allowed us to establish baselines of health indicators to inform outbreak contingency plans.

Dom, Elizabeth and I now co-direct this effort, which is known as the Gombe Ecosystem Health Project.

How does Gombe fit into the bigger picture of wildlife conservation? 

As a result of Jane Goodall’s initial observations of disease outbreaks impacting Gombe’s chimpanzees, it became apparent that infectious diseases have the capacity to threaten the conservation of endangered species.

Some people call Gombe “a living laboratory.” It’s unique in the sense that it’s a place where there has been long-term data collection on the behavior patterns of chimpanzees, and for the past 15 years we’ve been collecting all this data on their health.

Methods have been developed at Gombe that allow us to monitor chimpanzee health non-invasively, through fecal sampling, so that we don’t have to dart the animals and tranquilize them to take blood samples. Many of the tools and approaches developed at Gombe have the capacity to manage disease-related threats to other wildlife populations globally.

Ashley Sullivan from the Jane Goodall Institute contributed to this report.

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Studying how genetic differences contribute to addiction

Psychology professor Rohan Palmer has earned a $2.4 million grant to examine why some people become addicted to alcohol or drugs, while others don't. Emory Photo/Video

By April Hunt
Emory Report

Rohan Palmer, an assistant professor of psychology in Emory College, started on the path to becoming a researcher as an undergraduate, when he worked in a lab studying whether female mice could overcome their anxiety to leave the safety of the nest to retrieve babies that he and other researchers had moved away.

Intriguingly, the work showed that some strains of mice performed very differently than others in overcoming their emotions to perform their motherly duties. Moreover, females exposed to more testosterone in the uterus performed worst at this and other maternal tasks.

“It was understanding behavior at its core,” says Palmer, now an expert in the field of behavioral genetics. “What helps us understand what makes us individuals better than looking at the environment and the biology?”

Palmer now runs his own behavioral genetics lab at Emory that turns that question to one of today’s most pressing issues: What makes some people addicted to drugs or alcohol, and not others?

His highly innovative approach, to find and characterize the layer of biology that combines with factors such as environment to find an answer, has earned him a 2017 Avenir Award for Genetics or Epigenetics of Substance Abuse Disorders (DP1) from the National Institutes of Health Director’s Pioneer Award program.

The five-year, $2.34 million award is among a handful of grants given to recognize “highly creative” scientists from the nation’s top universities and to encourage high-impact approaches to the broad area of biomedical and behavioral science.

“This is a special award, more so because very few beginning investigators receive this honor,” says Ronald Calabrese, the College’s senior associate dean for research.

Read more in Emory Report.

Aversion to holes driven by disgust, not fear, study finds

Clusters of holes, such as those of a lotus seed pod, may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection. (Photo by Peripitus/Wikipedia Commons.)

By Carol Clark

Trypophobia, commonly known as “fear of holes,” is linked to a physiological response more associated with disgust than fear, finds a new study published in PeerJ.

Trypophobia is not officially recognized in the American Psychiatric Association’s Diagnostic and Statistical Manuel of Mental Disorders (DSM). Many people, however, report feeling an aversion to clusters of holes — such as those of a honeycomb, a lotus seed pod or even aerated chocolate.

“Some people are so intensely bothered by the sight of these objects that they can’t stand to be around them,” says Stella Lourenco, a psychologist at Emory University whose lab conducted the study. “The phenomenon, which likely has an evolutionary basis, may be more common than we realize.”

Previous research linked trypophobic reactions to some of the same visual spectral properties shared by images of evolutionarily threatening animals, such as snakes and spiders. The repeating pattern of high contrast seen in clusters of holes, for example, is similar to the pattern on the skin of many snakes and the pattern made by a spider’s dark legs against a lighter background.

“We’re an incredibly visual species,” says Vladislav Ayzenberg, a graduate student in the Lourenco lab and lead author of the PeerJ study. “Low-level visual properties can convey a lot of meaningful information. These visual cues allow us to make immediate inferences — whether we see part of a snake in the grass or a whole snake — and react quickly to potential danger.”

It is well-established that viewing images of threatening animals generally elicits a fear reaction in viewers, associated with the sympathetic nervous system. The heart and breathing rate goes up and the pupils dilate. This hyperarousal to potential danger is known as the fight-or-flight response.

The researchers wanted to test whether this same physiological response was associated with seemingly innocuous images of holes.

They used eye-tracking technology that measured changes in pupil size to differentiate the responses of study subjects to images of clusters of holes, images of threatening animals and neutral images.

Unlike images of snakes and spiders, images of holes elicited greater constriction of the pupils — a response associated with the parasympathetic nervous system and feelings of disgust.

“On the surface, images of threatening animals and clusters of holes both elicit an aversive reaction,” Ayzenberg says. “Our findings, however, suggest that the physiological underpinnings for these reactions are different, even though the general aversion may be rooted in shared visual-spectral properties.”

In contrast to a fight-or-flight response, gearing the body up for action, a parasympathetic response slows heart rate and breathing and constricts the pupils. “These visual cues signal the body to be cautious, while also closing off the body, as if to limit its exposure to something that could be harmful,” Ayzenberg says.

The authors theorize that clusters of holes may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection.

The subjects involved in the experiments were college students who did not report having trypophobia. “The fact that we found effects in this population suggests a quite primitive and pervasive visual mechanism underlying an aversion to holes,” Lourenco says.

Since the time of Darwin, scientists have debated the relation between fear and disgust. The current paper adds to the growing evidence that — while the two emotions are on continuums and occasionally overlap — they have distinct neural and physiological underpinnings.

“Our findings not only enhance our understanding of the visual system but also how visual processing may contribute to a range of other phobic reactions,” Ayzenberg says.

A third co-author of the study is Meghan Hickey. She worked on the experiments as an undergraduate psychology major, through the Scholarly Inquiry and Research at Emory (SIRE) program, and is now a medical student at the University of Massachusetts.

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New methods reveal the biomechanics of blood clotting

An electron micrograph shows a red blood cell, an activated platelet (in yellow) and a white blood cell. The ability to map the magnitude and orientation of forces on a cell provides a new tool for investigating not just blood clotting but a range of biomechanical processes. (NCI photo)

By Carol Clark

Platelets are cells in the blood whose job is to stop bleeding by sticking together to form clots and plug up a wound. Now, for the first time, scientists have measured and mapped the key molecular forces on platelets that trigger this process.

The extensive results are published in two separate studies, in the Proceedings of the National Academy of Sciences (PNAS) and in Nature Methods. “We show conclusively that, in order to activate clotting, the cell needs a targeted force of a magnitude of just a few piconewtons — or a force about a billion times less than the weight of a staple,” says Khalid Salaita, associate professor in Emory University’s Department of Chemistry and the lead author of the studies. “The real surprise we found is that platelets care about the direction of that force and that it has to be lateral. They’re very picky. But they should be picky because otherwise they might accidentally create a clot. That’s what causes strokes.”

Fibrinogen, the third most abundant protein in blood, acts like glue to stick platelets together as a clot forms. Each platelet has about 70,000 copies of a receptor for fibrinogen on its surface. These receptors can work like grappling hooks to latch onto fibrinogen.

“What was puzzling,” Salaita explains, “is that platelets, despite having all these receptors, do not normally latch onto the abundant fibrinogen. They keep flowing past it until you have an injury and fibrinogen becomes anchored. Then the platelets rapidly bind to fibrinogen allowing platelets to aggregate and for clotting to proceed.”



The Salaita lab is a leader in visualizing and mapping the mechanical forces applied by cells. In order to explore the biomechanics of blood clotting, the lab teamed up with physician and biomedical engineer Wilbur Lam, an expert in hematology at Emory’s School of Medicine. Both Salaita and Lam are also affiliated with Emory’s Winship Cancer Institute and the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech.

In initial experiments, for the PNAS paper, the Salaita lab anchored fibrinogen ligands onto a lipid membrane. On this surface, the ligands could slip and slide laterally, but resisted motion perpendicular to the surface — similar to the way a hockey puck slides easily over the surface of an ice rink but is harder to lift off of the plane of ice. The researchers then introduced platelets to this surface and experiments showed that the platelets failed to activate and stick together.

In contrast, when the fibrinogen ligands were anchored to a glass slide and unable to move laterally, the platelets rapidly activated. Using tension-imaging technology it developed, the Salaita lab showed that the platelets applied forces between five and 20 piconewtons to initiate activation.

“Platelets have to walk this tightrope between stopping bleeding quickly and accurately during an injury but avoiding unnecessary clotting. Mistakes could be fatal,” Salaita says. “We think they use this lateral force signal like a safety lock to prevent unnecessary clotting.”

Blood vessels are lined with endothelial cells and an injury exposes the fibrous matrix underneath these cells, Salaita explains. Platelets and fibrinogen in the blood can then stick to the injury site.

Salaita theorizes that when a platelet encounters stuck fibrinogen molecules, the platelet tugs on this fibrinogen as a way to test it. The resulting force generates a potent signal to activate platelets and that allows them to grab the fibrinogen from the blood, driving the process of clumping with other platelets.

The abnormal clotting that leads to strokes, and the uncontrollable bleeding of hemophilia, may be related to malfunctions in this biomechanical mechanism, he adds.

In 2011, the Salaita lab developed a fluorescence-sensor method for mapping cell mechanics. Alexa Mattheyses, a cell biologist at Emory’s School of Medicine and Winship Cancer Institute, teamed with the lab to test whether fluorescence polarization could be applied to map the direction of cell forces and provide further insights into the biomechanics of blood clotting.

The results, published in the Nature Methods paper, showed that they could.

Mattheyses “is a guru of fluorescence polarization,” Salaita says. She built a dedicated microscope that allowed mapping force direction at piconewton resolution. She also worked with Joshua Brockman and Aaron Blanchard, graduate students in the Salaita lab, to develop the new imaging technology.

The technique uses DNA molecules as force probes, which behave like molecular ropes and extend in the direction that a cellular force pulls. A series of microscopy images captures the orientation of the DNA, which can then be used to calculate the orientation of piconewton cell forces.

“We got really good at measuring and mapping magnitude, using fluorescence to see how stretched a polymer was,” Salaita says. “Now we can also see which direction a polymer is pointing, in three dimensions.”

Experiments revealed that as platelets begin sticking together to form a clot they contract toward a line, or central axis, in each cell. They do not, however, pull together toward a shared central axis. “It’s similar to having a group of people in a room that are all facing different directions,” Salaita explains. “When they join hands and everybody pulls inward you still get a cluster but the direction that each person is pulling is randomly oriented.”

The ability to map both the magnitude and orientation of forces on a cell provides a powerful tool for investigating not just blood clotting but a range of biomechanical processes, from immune cell activation and embryo development to the replication and spread of cancer cells.

“We’ve developed a completely new way to see things that were not visible before,” Salaita says. “It’s a basic tool with broad applications to help understand why cells are doing things and maybe predict what they’re going to do next.”

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