Thursday, May 5, 2022

Ancient DNA gives new insights into 'lost' Indigenous people of Uruguay

A sculpture commemorates the Indigenous people of Uruguay in the capital of Montevideo. Archeological evidence for human settlement of the area goes back 10,000 years. (Photo by Maximasu via Wikimedia Commons)

By Carol Clark

The first whole genome sequences of the ancient people of Uruguay provide a genetic snapshot of Indigenous populations of the region before they were decimated by a series of European military campaigns. PNAS Nexus published the research, led by anthropologists at Emory University and the University of the Republic, Montevideo, Uruguay. 

“Our work shows that the Indigenous people of ancient Uruguay exhibit an ancestry that has not been previously detected in South America,” says John Lindo, co-corresponding author and an Emory assistant professor of anthropology specializing in ancient DNA. “This contributes to the idea of South America being a place where multi-regional diversity existed, instead of the monolithic idea of a single Native American race across North and South America.” 

The analyses drew from a DNA sample of a man that dated back 800 years and another from a woman that went back 1,500 years, both well before the 1492 arrival of Christopher Columbus in the Americas. The samples were collected from an archeological site in eastern Uruguay by co-corresponding author Gonzalo Figueiro, a biological anthropologist at the University of the Republic. 

The results of the analyses showed a surprising connection to ancient individuals from Panama — the land bridge that connects North and South America — and to eastern Brazil, but not to modern Amazonians. These findings support the theory proposed by some archeologists of separate migrations into South America, including one that led to the Amazonian populations and another that led to the populations along the East coast. 

“We’ve now provided genetic evidence that this theory may be correct,” Lindo says. “It runs counter to the theory of a single migration that split at the foot of the Andes.” 

Archeological evidence 

The archeological evidence for human settlement of the area now known as Uruguay, located on the Atlantic coast south of Brazil, goes back more than 10,000 years. European colonizers made initial contact with the Indigenous people of the region in the early 1500s. 

During the 1800s, the colonizers launched a series of military campaigns to exterminate the native peoples, culminating in what is known as the massacre at Salsipuedes Creek, in 1831, which targeted an ethnic group called the CharrĂșa. At that time, the authors write, the term CharrĂșa was being applied broadly to the remnants of various hunter-gatherer groups in the territory of Uruguay. 

“Through these first whole genome sequences of the Indigenous people of the region before the arrival of Europeans, we were able to reconstruct at least a small part of their genetic prehistory,” Lindo says. 

The work opens the door to modern-day Uruguayans seeking to potentially link themselves genetically to populations that existed in the region before European colonizers arrived. “We would like to gather more DNA samples from ancient archeological sites from all over Uruguay, which would allow people living in the country today to explore a possible genetic connection,” Lindo says. 

Focusing on little-explored human lineages 

The Lindo ancient DNA lab specializes in mapping little-explored human lineages of the Americas. Most ancient DNA labs are located in Europe, where the cooler climate has better preserved specimens. 

Less focus has been put on sequencing ancient DNA from South America. One reason is that warmer, more humid climates throughout much of the continent have made it more challenging to collect usable ancient DNA specimens, although advances in sequencing technology are helping to remove some of these limitations. 

“If you’re of European descent, you can have your DNA sequenced and use that information to pinpoint where your ancestors are from down to specific villages,” Lindo says. “If you are descended from people Indigenous to the Americas you may be able to learn that some chunk of your genome is Native American, but it’s unlikely that you can trace a direct lineage because there are not enough ancient DNA references available.” 

Further complicating the picture, he adds, is the massive disruption caused by the arrival of Europeans given that many civilizations were destroyed and whole populations were killed. 

By collaborating closely with Indigenous communities and local archeologists, Lindo hopes to use advanced DNA sequencing techniques to build a free, online portal with increasing numbers of ancient DNA references from the Americas, to help people better explore and understand their ancestry. 

Co-authors of the current paper include Emory senior Rosseirys De La Rosa, Andrew Luize Campelo dos Santos (the Federal University of Penambuco, Recife, Brazil), Monica Sans (University of the Republic, Montevideo, Uruguay), and Michael De Giorgio (Florida Atlantic University). 

The work was funded by a National Science Foundation CAREER Grant. 

Related:

Ancient DNA lab maps little-explored human lineages

Ancient DNA from Sudan shines new light on Nile Valley past

'Potato gene' reveals how ancient Andeans adapted to starchy diet 

Wednesday, April 6, 2022

Computerized, rolling DNA motors move molecular robotics to next level

"I love the idea of using something that's innate in all of us to engineer new forms of technology," says Emory graduate student Selma Piranej, shown with a cell phone microscope set up to observe the rolling DNA-based motors.
 

By Carol Clark

Chemists integrated computer functions into rolling DNA-based motors, opening a new realm of possibilities for miniature, molecular robots. Nature Nanotechnology published the development, the first DNA-based motors that combine computational power with the ability to burn fuel and move in an intentional direction. 

“One of our big innovations, beyond getting the DNA motors to perform logic computations, is finding a way to convert that information into a simple output signal — motion or no motion,” says Selma Piranej, an Emory University PhD candidate in chemistry, and first author of the paper. “This signal can be read by anyone holding a cell phone equipped with an inexpensive magnifying attachment.”

“Selma’s breakthrough removes major roadblocks that stood in the way of making DNA computers useful and practical for a range of biomedical applications,” says Khalid Salaita, senior author of the paper and an Emory professor of chemistry at Emory University. Salaita is also on the faculty of the Wallace H. Coulter Department of Biomedical Engineering, a joint program of Georgia Tech and Emory. 

The motors can sense chemical information in their environment, process that information, and then respond accordingly, mimicking some basic properties of living cells. 

“Previous DNA computers did not have directed motion built in,” Salaita says. “But to get more sophisticated operations, you need to combine both computation and directed motion. Our DNA computers are essentially autonomous robots with sensing capabilities that determine whether they move or not.” 

The motors can be programmed to respond to a specific pathogen or DNA sequence, making them a potential technology for medical testing and diagnostics. Another key advance is that each motor can operate independently, under different programs, while deployed as a group. That opens the door for a single massive array of the micron-sized motors to carry out a variety of tasks and perform motor-to-motor communication. 

“The ability for the DNA motors to communicate with one another is a step towards producing the kind of complex, collective action generated by swarms of ants or bacteria,” Salaita says. “It could even lead to emergent properties.” 

The high speed of the rolling DNA-based motor allows a simple smart phone microscope to capture its motion through video.
 

DNA nanotechnology takes advantage of the natural affinity for the DNA bases A, G, C and T to pair up with one another. By moving around the sequence of letters on synthetic strands of DNA, scientists can get the strands to bind together in ways that create different shapes and even build functioning machines. 

The Salaita lab, a leader in biophysics and nanotechnology, developed the first rolling DNA-based motor in 2015. The device was 1,000 times faster than any other synthetic motor, fast-tracking the burgeoning field of molecular robotics. Its high speed allows a simple smart phone microscope to capture its motion through video. 

The motor’s “chassis” is a micron-sized glass sphere. Hundreds of DNA strands, or “legs” are allowed to bind to the sphere. These DNA legs are placed on a glass slide coated with the reactant RNA, the motor’s fuel. The DNA legs are drawn to the RNA, but as soon as they set foot on it they erase it through the activity of an enzyme that is bound to the DNA and destroys only RNA. As the legs bind and then release from the substrate, they keep guiding the sphere along. 

When Piranej joined the Salaita lab in 2018, she began working on a project to take the rolling motors to the next level by building in computer programming logic. 

“It’s a major goal in the biomedical field to take advantage of DNA for computation,” Piranej says. “I love the idea of using something that’s innate in all of us to engineer new forms of technology.” 

DNA is like a biological computer chip, storing vast amounts of information. The basic units of operation for DNA computation are short strands of synthetic DNA. Researchers can change the “program” of DNA by tweaking the sequences of AGTC on the strands. 

“Unlike a hard, silicon chip, DNA-based computers and motors can function in water and other liquid environments,” Salaita says. “And one of the big challenges in fabricating silicon computer chips is trying to pack more data into an ever-smaller footprint. DNA offers the potential to run many processing operations in parallel in a very small space. The density of operations you could run might even go to infinity.” 

Synthetic DNA is also biocompatible and cheap to make. “You can replicate DNA using enzymes, copying and pasting it as many times as you want,” Salaita says. “It’s virtually free.” 

Limitations remain, however, in the nascent field of DNA computation. A key hurdle is making the output of the computations easily readable. Current techniques heavily rely on tagging DNA with fluorescent molecules and then measuring the intensity of emitted light at different wavelengths. This process requires expensive, cumbersome equipment. It also limits the signals that can be read to those present in the electromagnetic spectrum. 

"Developing devices for biomedical applications is especially rewarding because it's a chance to make a big impact in people's lives," says Piranej, shown during a trip to San Franciso.

Although trained as a chemist, Piranej began learning the basics of computer science and diving into bioengineering literature to try to overcome this hurdle. She came up with the idea of using a well-known reaction in bioengineering to perform the computation and pairing it with the motion of the rolling motors. 

The reaction, known as toehold-mediated strand displacement, occurs on duplex DNA — two complementary strands. The strands are tightly hugging one another except for one loose, floppy end of a strand, known as the toe hold. The rolling motor can be programmed by coating it with duplex DNA that is complementary to a DNA target — a sequence of interest. When the molecular motor encounters the DNA target as it rolls along its RNA track, the DNA target binds to the toe hold of the duplex DNA, strips it apart, and anchors the motor into place. The computer read out becomes simply “motion” or “no motion.” 

“When I first saw this concept work during an experiment, I made this really loud, excited sound,” Piranej recalls. “One of my colleagues came over and asked, ‘Are you okay?’ Nothing compares to seeing your idea come to life like that. That’s a great moment.” 

These two basic logic gates of “motion” or “no motion” can be strung together to build more complicated operations, mimicking how regular computer programs build on the logic gates of “zero” or “one.” 

Piranej took the project even further by finding a way to pack many different computer operations together and still easily read the output. She simply varied the size and materials of the microscopic spheres that form the chassis for the DNA-based rolling motors. For instance, the spheres can range from three to five microns in diameter and be made of either silica or polystyrene. Each alteration provides slightly different optical properties that can be distinguished through a cell phone microscope.

The Salaita lab is working to establish a collaboration with scientists at the Atlanta Center for Microsystems Engineered Point-of-Care Technologies, an NIH-funded center established by Emory and Georgia Tech. They are exploring the potential for the use of the DNA-computing technology for home diagnostics of COVID-19 and other disease biomarkers. 

“Developing devices for biomedical applications is especially rewarding because it’s a chance to make a big impact in people’s lives,” Piranej says. “The challenges of this project have made it more fun for me,” she adds. 

Related:

NIH grant funds Emory work on indoor air sensor for SARS-CoV-2 

New DNA motor breaks speed record for nano machines

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

Thursday, March 17, 2022

Monarch butterflies increasingly plagued by parasites, study shows

"Our findings suggest that tens of millions of eastern monarch butterflies are getting sick and dying each year from these parasites," says Emory evolutionary biologist Jaap de Roode, senior author of the study.

By Carol Clark

Monarch butterflies, one of the most iconic insects of North America, are increasingly plagued by a debilitating parasite, a major new analysis shows. The Journal of Animal Ecology published the findings, led by scientists at Emory University. 

The analysis drew from 50 years of data on the infection rate of wild monarch butterflies by the protozoan Ophryocystis elektrosirrha, or O.E. The results showed that the O.E. infection rate increased from less than one percent of the eastern monarch population in 1968 to as much as 10 percent today. 

“We’re seeing a significant change in a wildlife population with a parasitism rate steadily rising from almost non-existent to as high as 10 percent,” says Ania Majewska, first author of the paper and a post-doctoral fellow in Emory’s Department of Biology. “It’s a signal that something is not right in the environment and that we need to pay attention.” 
 
The O.E. parasite invades the gut of the monarch caterpillars. If the adult butterfly leaves the pupal stage with a severe parasitic infection, it begins oozing fluids from its body and dies. Even if the butterflies survive, as in case of a lighter infection, they do not fly well or live as long as uninfected ones. 

The rise in parasitism, the researchers warn, may endanger the mass migration of the monarchs, one of the most spectacular displays in the animal kingdom, involving hundreds of millions of butterflies. Each fall, the western monarch population flies hundreds of miles down the Pacific Coast to spend the winter in California. Meanwhile, on the other side of the Rocky Mountains, eastern monarchs fly from as far north as the U.S.-Canadian border to overwinter in Central Mexico, covering as much as 3,000 miles. 

“Our findings suggest that tens of millions of eastern monarch butterflies are getting sick and dying each year from these parasites,” says Jaap de Roode, Emory professor of biology and senior author of the study. “If the infection rates keep going up, fewer and fewer monarchs will be able to survive to migrate to their overwintering sites.” 

One contributor to the rise in the parasitism rate is the increased density of monarchs in places where they lay their eggs, the study finds. The researchers posit that the increased density may be due to many factors, including the loss of wildlife habitat; the widespread planting of exotic, non-native species of milkweed; and by people raising monarchs in large numbers in confined spaces.

Co-authors of the paper are Sonia Altizer and Andrew Davis of the University of Georgia Odum School of Ecology. 

"Monarchs are incredible animals," says Ania Majewska, first author of the study, shown in the Monarch Butterfly Biosphere Reserve in Mexico.

Majewska began studying monarchs eight years ago while a graduate student at the University of Georgia. She joined the De Roode lab at Emory in 2019, funded by the NIH program Fellowships in Research and Science Teaching. 

“Monarchs are incredible animals,” she says. “Each one is only as heavy as a paperclip but they can fly so far and they are incredibly resilient.” 

The Monarch Butterfly Biosphere Reserve in Mexico, where the eastern monarchs overwinter in pine and fir forests, is a World Heritage Site and an important generator of tourism income. “The trees can become so heavy with monarchs that sometimes branches break off and fall,” Majewska says. “When sunlight hits the clusters the monarchs explode like confetti. It’s a magical sight.” 

The butterflies arrive in large numbers in Mexico near the Day of the Dead, when families gather around the gravesites of their loved ones. For traditional cultures in the region, monarchs have come to represent the souls of ancestors returning to visit for the celebrations. 

In addition to the monarch migration’s natural beauty, economic and cultural significance, it plays an ecological role, as the butterflies pollinate plants and provide food for wasps, ants and other invertebrate predators. 

Birds, however, tend to avoid the monarchs, as the butterfly’s striking coloration of orange, black and white is a warning sign that it may be poisonous to them. 

Monarchs overwintering on a tree in Mexico. (Photo by Jaap de Roode)

When monarchs leave their overwintering sites in the spring, they fly north and lay their eggs. Their caterpillars feed on any of dozens of species of milkweed plants, including some species that contain high levels of cardenolides. These chemicals do not harm the caterpillars, but make them toxic to some predators even after they emerge as adults from their chrysalises. 

In 2010, Jaap de Roode discovered that monarchs also use cardenolides as a kind of drug. Experiments in his lab showed that a female infected with the O.E. parasite prefers to lay her eggs on a toxic species of milkweed, rather than a non-toxic species. Uninfected female monarchs, however, showed no preference. While cardenolides do not cure the caterpillars of parasites, they can lessen the severity of an infection. 

For the current paper, the researchers wanted to investigate the O.E. infection rate in monarch populations over time. They accessed multiple available data sets, which were mostly for the eastern monarchs. The data included samples going back to 1968 collected by the late Lincoln Brower, an entomologist who specialized in monarchs, and by other researchers through the decades. 

The results showed the rise in the parasitism rate remained low in the eastern monarch population for several decades before shooting up beginning in the 2000s, then making a slight dip in recent years.

Monarchs caterpillars feed exclusively on milkweed plants. (Photo by Jaap de Roode)

Among the factors that may be contributing to the increased monarch density associated with the rise in parasitism, the researchers note, is the loss of natural habitat and agricultural practices that have reduced the places where milkweed is found. Milkweed used to proliferate amid crops in the Midwest, for instance, but farmers increasingly use genetically engineered herbicide-resistant crops. That allows them to spray their fields to eradicate weeds. 

Since milkweed is the sole source of food for monarch caterpillars, and fewer of the plants are available, the female monarchs must cluster more densely to lay their eggs and the butterfly “nurseries” become more crowded with caterpillars. 

“One thing that the COVID-19 pandemic taught us is that social distancing can help reduce the spread of an infectious disease,” de Roode says. “The same holds true for monarchs and the O.E. parasite.” 

Around the year 2000, the researchers note, conservation groups began planting exotic species of milkweed to try to support the monarch population, which has been declining. Ironically, this conservation effort may have fueled more parasitism. “The exotic species of milkweed tend to have more cardenolides than native species,” Majewska explains, “so infected female monarchs may be seeking the exotic species out, adding to the density problem.” 

The researchers further hypothesize that people raising monarch caterpillars in large numbers — to support conservation efforts or for commercial purposes — may be keeping them in crowded conditions that foster the spread of the parasite. 

“Ultimately, a continuing rise in the monarch’s parasitic infection rate could cause the species to suffer significantly,” Majewska says. “If tens of millions of them are dying annually from parasitic infections, then an extreme weather event during the winter in Mexico might reduce the population to a level that could be dangerous for their genetic diversity.” 

“Parasitism is often overlooked in conservation efforts,” de Roode adds, “but our findings show how parasites can have a massive impact on wildlife.” 

The research was supported by the National Institutes of Health and the National Science Foundation.

Related:

Wednesday, March 16, 2022

Heartland virus identified in lone star ticks in Georgia

The lone star tick, named for the distinctive white spot on its back, is the most common tick in Georgia.  Emory researchers detected Heartland virus in three different specimen samples of lone star ticks collected in central Georgia. (CDC/James Gathany)

By Carol Clark

Heartland virus is circulating in lone star ticks in Georgia, scientists at Emory University have found, confirming active transmission of the virus within the state. The journal Emerging Infectious Diseases published the findings, which include a genetic analysis of the virus samples, isolated from ticks collected in central Georgia. 

The research adds new evidence for how the tick-borne Heartland virus, first identified in Missouri in 2009, may evolve and spread geographically and from one organism to another. 

“Heartland is an emerging infectious disease that is not well understood,” says Gonzalo Vazquez-Prokopec, associate professor in Emory’s Department of Environmental Sciences and senior author of the study. “We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem.” 

Vazquez-Prokopec is a leading expert in vector-borne diseases — infections transmitted from one organism to another by the bite of a vector, such as a tick or mosquito. 

Yamila Romer, a former post-doctoral fellow in the Vazquez-Prokopec lab, is first author of the new paper. Co-author Anne Piantadosi, assistant professor in Emory School of Medicine’s Department of Pathology and Laboratory Medicine, conducted the genetic analyses. 

"Ticks are both fascinating and terrifying," says study co-author Steph Bellman, shown in the field with a vial of ticks. "They represent a large threat to human health that a lot of people may not realize." Bellman is an MD/Phd student in Emory's School of Medicine and Rollins School of Public Health.

The study detected Heartland virus in three different specimen samples of lone star ticks — collected in different locations and at different times — and including both the nymph and adult stages of the ticks.

The genetic analysis of the three viral samples showed that their genomes are similar to one another, but much different from the genomes of Heartland virus samples from outside the state. “These results suggest that the virus may be evolving very rapidly in different geographic locations, or that it may be circulating primarily in isolated areas and not dispersing quickly between those areas,” Vazquez-Prokopec says. 

The Heartland virus was discovered in 2009 in northwest Missouri after two local men were hospitalized with high fevers, diarrhea, muscle pains, low counts of white blood cells and platelets, and other symptoms similar to known tick-borne diseases. Researchers soon realized the men were infected with a novel virus, which was christened Heartland, and later traced to lone star ticks. Further studies found antibodies to the virus in blood samples from deer and some other wild mammals. 

The Centers for Disease Control and Prevention currently recognizes 18 tick-borne diseases in the United States, many of them newly emerging. One of the most well-known tick-borne illnesses is Lyme disease, caused by a bacterium, which in recent decades has grown into the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, is the vector for transmission of the bacteria that causes Lyme disease and the white-footed mouse is the primary reservoir for the bacterium. The tick larvae can become infected when they feed on the blood of the mice and other small mammals and birds that may be harboring the bacterium. The infected larvae grow into nymphs and adult ticks that can then move into other hosts, including deer and humans. 

While the complex transmission cycle for Lyme disease is well characterized, many questions remain about how the Heartland virus moves among different species. 

The researchers used flags of white flannel to collect the tick specimens.

Since it was first discovered in 2009, more than 50 cases of Heartland virus have been identified in people from 11 states in the Midwest and Southeast, according to the Centers for Disease Control and Prevention. Many of the identified cases were severe enough to require hospitalization and a few individuals with co-morbidities have died. The actual disease burden is believed to be higher, however, since Heartland virus is still not well known and tests are rarely ordered for it. 

A retroactive analysis uncovered a single confirmed human infection of Heartland virus in Georgia, in a Baldwin County resident who died with what was then an unidentified illness in 2005. The human case prompted analysis of serum samples collected in past years from white-tailed deer in central Georgia. The results showed that deer from that area have been exposed to the Heartland virus since at least 2001. 

To better assess the risk for human disease in the area, Vazquez-Prokopec wanted to learn whether lone star ticks are currently carrying Heartland virus in central Georgia. 

Members of the field research team collected ticks from the rural landscape near the Piedmont National Wildlife Refuge. Even during the hot Georgia summers, team members wore long shirts and long pants tucked into long socks, with the top of the socks sealed with duct tape. They further protected themselves with bug spray and by conducting visual checks for ticks on themselves before and after leaving the field. 

The lone star tick, named for a distinctive white spot on its back, is the most common tick in Georgia and is widely distributed in wooded areas across the Southeast, Eastern and Midwest United States. They are tiny, about the size of a sesame seed in the nymph stage, and barely a quarter-of-an-inch in diameter as adults. 

“Lone star ticks are so small that you may not feel them on you or even notice if you’ve been bitten by one,” says Steph Bellman, a co-author of the study. Bellman is an MD/PhD student in Emory’s School of Medicine and Rollins School of Public Health, focused on environmental health. 

A vial of ticks collected in the field.

The team used “flagging” as a collection technique. A flag of white flannel on a pole is swished in a figure-eight motion through the underbrush. “Every so often, you lay the flag down and use a pair of tweezers to remove any ticks that you find on it and put them into a vial,” Bellman explains. 

Through this painstaking method, the team collected nearly 10,000 specimens from sites in Georgia’s Putnam County and Jones County, both adjacent to Baldwin County. Specimens were separated into groups, each containing either five adults or 25 nymphs, then crushed and put into a solution to test for the presence of the Heartland virus. 

The results suggested that about one out of every 2,000 of the collected specimens carried the Heartland virus. One adult and one nymph sample collected on the same date tested positive from a site in Putnam County, a private property used for hunting. A second sample of adult ticks, collected on a different date from a stretch of woods along a highway in Jones County, also tested positive. 

The researchers are now expanding the scope of the work. They will collect ticks across Georgia for testing and conduct spatial analyses with the aim of understanding factors that may raise the risk for Heartland virus. 

“We want to start filling in the huge gaps in knowledge of the transmission cycle for Heartland virus,” Vazquez-Prokopec says. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.” 

Climate change is fueling warmer and shorter winters, increasing opportunities for some species of ticks to breed more frequently and to expand their ranges. Land-use changes are also strongly associated with tick-borne diseases, as more human habitats encroach on wooded areas and the loss of natural habitat forces wildlife to live in denser populations. 

“Ticks are both fascinating and terrifying,” Bellman says. “We don’t have effective ways to control them and they are a vector for many nasty diseases. They represent a large threat to human health that a lot of people may not realize.” 

The Asian longhorned tick is an invasive species that has been found in Georgia and 16 other states. (CDC/James Gathany)

The Prokopec Lab is also investigating the arrival of the Asian longhorned tick (Haemaphysalis longicornis) in Georgia, funded by a seed grant from the U.S. Department of Agriculture. 

Long established in China, Japan, Russia and parts of the Pacific, the Asian longhorned tick was first detected in the United States in 2018, in New Jersey. The tick has since spread to 17 states, including Georgia, where it was found on a farm in Pickens County in 2021. 

The Asian longhorned tick reproduces asexually and a single female can generate as many as 100,000 eggs, rapidly producing massive amounts of offspring that feed on livestock. So many ticks can be covering a single sheep or cow that the loss of blood physically weakens or, in extreme cases, kills the animal. 

The Asian longhorned tick also carries bacterial and viral pathogens that can infect humans, including severe fever with thrombocytopenia syndrome virus (SFTSV), also known as Dabie bandavirus. Human cases of SFTS, a hemorrhagic fever, emerged in China in 2011 and have since been identified in other parts of Asia. 

“We are investigating not only the potential agricultural impact of the Asian longhorned tick in Georgia, but the potential for this invasive tick to spread SFTS and other diseases to people,” Vazquez-Prokopec says. 

Of particular concern is the fact that the Heartland virus shares genomic similarities with SFTSV, he adds. 

“We will be gathering data to help support tick surveillance efforts by public health officials in Georgia,” Vazquez-Prokopec says. “Tick-borne diseases are a real and growing threat and the best way to deal with them is not to panic, but to do the science needed to learn everything we can about them.”  

Additional co-authors of the current paper include Uriel Kitron, professor in Emory’s Department of Environmental Sciences; Oscar Kirstein, an Emory post-doctoral fellow in the Prokopec Lab; Daniel Mead and Kalya Adcock, from the University of Georgia; and Zhuorn Wei, a former Emory research assistant. 

Funding for the work was provided by a grant from the Emory University Research Council.

Related:

Atlanta Science Fest celebrates the wonders all around us


A celebration of science once again takes metro Atlanta by storm with the return of the Atlanta Science Festival, ongoing through March 26. More than 100 activities, planned throughout the city, invite families to experience the thrills of discovery, from nature walks to expert talks and hands-on STEM learning opportunities. 

“The festival offers ways for people of all ages to learn something new and to spark a new interest,” says Meisa Salaita, the executive co-director of Science ATL, the non-profit organization that produces the Atlanta Science Festival. “You may not realize that your child has a secret knack for chemistry, or that you enjoy birdwatching, until getting immersed in it.” 

The Atlanta Science Festival, now in its ninth year, was co-founded by Emory, Georgia Tech and the Metro Atlanta Chamber.

Monday, February 28, 2022

Data-driven study digs into the state of U.S. farm livelihoods

"Farmers are fundamental to our survival, their work is risky and difficult, and ensuring their quality of life is necessary for U.S. agriculture to persist," says Emily Burchfield, Emory assistant professor of environmental sciences and lead author of the study.

By Carol Clark

U.S. agricultural systems are world leaders in the production of food, fuel and fiber. This high level of production enables U.S. consumers to spend an average of only 8.6 percent of their disposable income on food, a percentage that has been trending downward since 1960. Growing evidence, however, shows that many hidden costs of cheap food may be passed on through factors such as reduced nutritional content, environmental degradation and the diminishing livelihoods of U.S. farm operators. 

A major new study led by Emory University digs deeper into the question of why, despite the extraordinary productivity of U.S. agriculture, U.S. farm operators are systematically losing money. The journal Frontiers of Sustainable Food Systems published the analysis, which drew from publicly available data from the U.S. Department of Agriculture, the U.S. Bureau of Economic Analysis and other sources. 

“It’s not that agriculture as a sector is not profitable,” says Emily Burchfield, assistant professor in Emory’s Department of Environmental Sciences and lead author of the study. “It’s that, despite hard work and significant financial risk, many of the people who operate U.S. farms are not able to make a decent living at it.” 

Rising input costs, shrinking production values, commodity specialization and challenges to land access all appear to be connected to declining farm operator livelihoods, the study concludes. 

“We’ve shown in a quantitative, systematic way the extent to which these trends are happening and, in many cases, how they appear to be worsening,” Burchfield says. 

An online data repository

“People who work in the agricultural space already know that it is difficult to make a living as a farmer,” she adds. “In this paper, we’ve cleaned and merged tremendous amounts of data from multiple sources to bring key information together into one place. This allows us to tell a more complete and clear story about how and why this is happening at a national scale.” 

The researchers deposited the cleaned and merged data into a free, online repository (https://github.com/blschum/US-Farming-Data-Narrative) so that other agricultural stakeholders can easily access it. They hope that their “one-stop,” centralized data hub on farmer livelihoods will serve as an educational tool and inspire more research into the topic. 

The USDA reported in 2020 that the average funds generated by farm operators to meet living expenses and debt obligations, after accounting for production expenses, have been negative for nine out of the last 10 years. In 2017, for instance, median net-cash farm income was $1,035 in the red per farm household in the country. 

Paying to farm

In many regions of the United States, the authors write, farm operators actually have to pay to engage in the labor- and time-intensive act of operating a farm. 

“What we were really surprised to find in the data is that the low, or negative, median farm operator income applies even when you factor in government subsidies,” Burchfield says. “Given that the federal government is subsidizing farming with billions of dollars annually, it raises the question of how we might do so more effectively. How are we going to convince folks to continue growing our food if they are locked into a system where they can’t make money?” 

Burchfield’s research combines spatial-temporal, social and environmental data to understand the future of food security in the United States, including the consequences of a changing climate. 

Co-authors of the current paper include: Britta Schumacher, a former Emory research assistant in Burchfield’s lab; Andrea Rissing, an Emory post-doctoral fellow in the lab; and Kaitlyn Spangler, a post-doctoral fellow at Penn State. 

Relying on off-farm income

Understanding how much income individual farms are losing on average is complicated by farm households often having a family member bringing in income through a non-farm occupation, Burchfield notes. In 2019, the USDA reported that on-farm production contributes to less than 25 percent of farm household income, on average, with the remaining 75 percent earned off-farm. This suggests that many farmers rely on off-farm income to stay afloat. 

“Farming is one of the hardest jobs on the planet,” Burchfield says, “and it’s going to get even harder due to climate change. The combination of more gradual shifts in average climate conditions, and the increased prevalence of extreme weather events, presents a serious challenge to farmers.” 

These ongoing challenges, the authors argue, require an urgent rethinking of how federal subsidies can play a role in encouraging and supporting new, adaptive approaches to agriculture. 

U.S. farm operations currently cover approximately 900 million cultivated acres, more than half of the nation’s land area. And three crops — corn, soy and wheat — are cultivated exclusively on more than two thirds of agricultural acres. 

“A lack of crop diversification can make farming increasingly brittle and less adaptable,” Burchfield says. “Climate change, meanwhile, makes the need for innovation and adaptation more crucial and inevitable.” 

The paper also highlights the lack of diversification among farm operators. Statistically, the “average” U.S. farmer is a 58-year-old white male. Those not identifying as white currently operate about 7 percent of farmland representing just 5 percent of operations. Only 1.4 percent of operators identify as Black, and these operators are heavily concentrated in the Southeast. And, on average, white operators receive twice as much from federal subsidy programs ($14,000 per farm) as Black operators ($6,400 per farm). 

A call for diversity of people, plants and practices

“We need better data to track the persistent inequities at the intersection of race, class and livelihoods in the agriculture space,” Burchfield says. 

She recommends finding ways to support the diversity of people, plants and practices in the national farm landscape to help address the growing issues of agricultural sustainability and climate change. “Small-scale experimentation and the emergence of grassroots alternatives along with technical innovations are all needed in order to better weather the challenges,” she says. 

Burchfield also cites the need for the availability of more fine-scale data on the livelihoods of farmers that goes beyond yields and acreage to cover issues such as access to health insurance. “Farmers are fundamental to our survival, their work is risky and difficult, and ensuring their quality of life is necessary for U.S. agriculture to persist,” she says. 

As Burchfield and her co-authors conclude: “Measuring and monitoring agricultural progress using only metrics of production, efficiency and revenue masks the lived realities of the humans operating our farms.” 

The research was supported in part by the U.S. Department of Agriculture and the National Science Foundation.

Related:

Diverse landcover boosts yields for major U.S. crops, study finds

Wednesday, February 23, 2022

Snail competition leads to fewer parasites that cause schistosomiasis

Field research was conducted in the Mwanza region of Tanzania where schistosomiasis is endemic. Running water is often not accessible in the area and many people use surface water ponds and hand-dug open wells that dot the clay-soil landscape. (Civitello Lab)

By Carol Clark

Schistosomiasis is a debilitating disease caused by a parasitic worm that develops in freshwater snails before infecting people. Knocking back snail populations with pesticides is one method to control the spread of the disease, also known as “snail fever.” 

A new study led by Emory University, however, shows that schistosome transmission can actually be highest when freshwater snail populations are low. The Proceedings of the National Academy of Sciences published the study, the first to demonstrate how the size of a freshwater snail population relates to its parasitic infection rate. 

“We’ve shown that the more snails you have in a freshwater source, the less dangerous each individual snail is, in terms of the number of parasites they’re releasing,” says David Civitello, an Emory assistant professor of biology and lead author of the study. “The incredible strength of our finding is that we’ve demonstrated the effect both in the field, using natural transmission sites, and in an experimental context, through outdoor laboratory experiments.” 

The research carries important implications for policies aimed at reducing the transmission of schistosomiasis. Considered one of the most significant of the neglected tropical diseases, the parasites that cause schistosomiasis currently infect more than 200 million people. 

“Our results suggest that if you apply a heavy dose of pesticides to reduce a snail population, the infectivity of the remaining snails might actually skyrocket,” Civitello says. “It’s basically impossible to kill every snail and so you set the stage for a rebound in infection risk. As the snail population begins to recover, our data tells us that this is a time with extremely high potential for transmission of the parasites to humans.” 

Click on the image for a detailed view of the transmission cycle of schistosomiasis. (CDC)

Previous laboratory experiments had found that when an individual freshwater snail infected with the parasite is well fed, it can generate as many as thousands more parasites per day compared to an underfed snail. In fact, an underfed infected snail may generate as few as a single parasite per day. 

“In general, when an animal needs to fight off an infection of some kind, it helps to have good nutrition to support the immune system,” Civitello says. “It appears to be the opposite case in these freshwater snails. When the snails are full of energy, it provides more nutrients for the parasites to steal from them and to reproduce.” 

Chronic infections of schistosomiasis cause considerable morbidity in sub-Saharan Africa and parts of the Middle East, South America and Southeast Asia. The disease cycles between humans and freshwater snails that live in water sources where people may bathe, wash their clothes and dishes and collect water for household use. Children, who like to play in water, are at especially high risk for infection. 

When eggs of the parasitic worms hatch in water, the larvae burrow into snails. Once the larvae develop into free-swimming worms, they burrow back out of their snail hosts and return to the water. These swimming worms can then burrow into the skin of people who come into contact with the water. 

Inside their human hosts, the worms enter blood vessels where they eat red blood cells for fuel as they mature into adults, pair up and mate. The female lays hundreds of thousands of eggs per day. Many of the eggs are excreted through feces and urine that re-enters water sources, continuing the cycle of infection. Some of the eggs, however, become lodged in the tissues and organs of their human hosts, leading to immune reactions and progressive damage to organs, such as the liver, the bladder, kidneys and the urogenital tract. One of the classic symptoms of a chronic infection is blood in the urine. 

"It's important to unite the ecology of a pathogen with human disease interventions and control measures," says David Civitello (center), shown in the field in Tanzania.

The prescription medication Praziquantel treats schistosomiasis but has limitations. “One problem is that the drug kills the mature adult schistosomes in humans, but not schistosomes that are only five or six weeks old and still maturing,” Civitello says. 

And a follow-up drug treatment does not eliminate the infection in the environment. 

“There is growing recognition in recent years that effective control of freshwater snails is needed, along with treatment of people, in order to disrupt transmission of schistosomiasis,” Civitello says. “In many cases, however, snail control policies have not been updated for decades.” 

For the PNAS paper, the researchers wanted to test whether the effect of food intake seen on the infection rate of individual freshwater snails in a laboratory would scale up to a population in the wild. Their hypothesis was that the larger the snail population, the more the snails would have to compete for food resources, lowering their energy levels along with their infectivity rate. 

They conducted field research in the Mwanza region of Tanzania where schistosomiasis is endemic, in collaboration with Tanzania’s National Institute for Medical Research Mwanza Center. Running water is not accessible in villages in the area and many people use surface water ponds and hand-dug open wells that dot the clay-soil landscape. 

The researchers found that snails collected from these water sources where the snail populations were dense were poorly infectious. In contrast, in the water sources where the snail population was low, their parasitic infection rate was high. 

The outdoor laboratory experiments, conducted in collaboration with the University of South Florida, further showed how the growth of a snail population from low to high density creates a burst of infectivity among the population before competition once again forces the infectivity to subside. 

“Our results suggest that, if you treat water bodies infrequently with a pesticide to control snails, you are likely to soon get a rebound of the snail population with a higher infectivity rate, potentially creating a surge of transmission to people,” Civitello. “It may be better either to not apply a pesticide at all, or else to apply the pesticide more frequently to prevent the snails rebounding.” 

The Civitello Lab plans to continue to collaborate with colleagues in Tanzania to gather more detailed data to help develop the most effective methods of freshwater snail control, for use in combination with other preventative methods for schistosomiasis. 

“It’s important to unite the ecology of a pathogen with human disease interventions and control measures,” Civitello says. 

Co-authors of the PNAS include: Safair Kinung’hi, Teckla Angelo, Moses Mahalila and Jenitha Charles (National Institute for Medical Research Mwanza Center); Jason Rohr (University of Notre Dame); Karena Nguyen, Rachel Hartman, Naima Starkloff and Lynda Bradley (Emory Department of Biology); Andres Manrique (University of Florida); Bryan Delius (Duquesne University); and Roger Nisbet (University of California, Santa Barbara). 

The work was supported by the U.S. National Institute of Allergy and Infectious Diseases, the National Science Foundation, the National Institutes of Health, and the Indiana Clinical and Translational Sciences Institute.

Related:

Water temperature key to schistosomiasis risk and prevention strategies

Thursday, February 17, 2022

Antibiotic used on food crops affects bumblebee behavior, lab study finds

A wild bumblebee visits a blossom. The current study involved lab experiments on a different species of bumblebee as a first step to understanding the potential effects of the agricultural use of streptomycin on pollinators.

By Carol Clark

An antibiotic sprayed on orchard crops to combat bacterial diseases slows the cognition of bumblebees and reduces their foraging efficiency, a laboratory study finds. Proceedings of the Royal Society B published the findings by scientists at Emory University and the University of Washington. 

The research focused on streptomycin, an antibiotic used increasingly in U.S. agriculture during the past decade. 

“No one has examined the potential impacts on pollinators of broadcast spraying of antibiotics in agriculture, despite their widespread use,” says Laura Avila, first author of the paper and a post-doctoral fellow in Emory’s Department of Biology. 

The current study was based on laboratory experiments using an upper-limit dietary exposure of streptomycin to bumblebees. It is not known whether wild bumblebees are affected by agricultural spraying of streptomycin, or whether they are exposed to the tested concentration in the field. 

“This paper is a first step towards understanding whether the use of streptomycin on food crops may be taking a toll on pollinators that benefit agriculture,” says Berry Brosi, senior author of the paper. Brosi began the work as a faculty member in Emory’s Department of Environmental Sciences and is currently with the University of Washington. 

Funded by a U.S. Department of Agricultural grant, the researchers will now conduct field studies where streptomycin is sprayed on fruit orchards. If a detrimental impact is found on bumblebees, the researchers hope to provide evidence to support recommendations for methods and policies that may better serve farmers. 

“Production of our food, farmer livelihoods and the health of pollinators are all tied together,” Brosi says. “It’s critically important to find ways to maintain agricultural production while also conserving the ecosystem services — including pollination — that a biodiverse ecosystem provides.” 

"I decided to become a bee biologist because I wanted to understand how the natural environment can influence agriculture and vice versa," says Laura Avila, above. Her work spans experiments in both the lab and field.

Based on established evidence, the researchers hypothesize that the negative impact of streptomycin on bumblebees seen in the lab experiments may be due to the disruption of the insects’ microbiome. 

“We know that antibiotics can deplete beneficial microbes, along with pathogens,” Avila says. “That’s true whether the consumers of the antibiotics are people, other animals or insects.” 

Avila is a member of the lab of Nicole Gerardo, Emory professor of biology and an entomologist who studies the co-evolution of insect-microbe systems. 

During the past decade, the spraying of antibiotics on U.S. crops has increased exponentially as farmers battle a rise in plant bacterial infections. “Fire blight” can turn the blossoms and shoots of apple and pear trees black, making them appear scorched by fire, and can also kill entire trees. “Citrus greening,” also known as “yellow dragon disease,” turns citrus fruits green, bitter and unusable and has devasted millions of acres of crops throughout the United States and abroad. 

“I’ve seen the struggle of making a living by producing crops, how expensive and difficult it can be to control diseases and pests,” says Avila, who grew up in a coffee-producing region of Costa Rica. 

Largely untouched forests bordered her family farm. “The diversity all around us fascinated me,” Avila says. “I decided to become a bee biologist because I wanted to understand how the natural environment can influence agricultural production and vice versa.” 

Seventy-five percent of the world’s food crops depend on pollination by at least one of more than 100,000 species of pollinators, including 20,000 species of bees, as well as other insects and vertebrates like birds and bats. And yet, many of the insect pollinator species, particularly bees, face risks of extinction. 

Previous studies have shown that the antibiotic tetracycline, used to treat pathogens in managed honeybee hives, can alter the gut microbiome of the insects and indirectly increase susceptibility to pathogens and mortality. Exposure to high oxytetracycline concentrations has also been found to have a similar effect on the bumblebee gut microbiome, decreasing their immunity to pathogens. And exposure to high doses of tetracycline have been found to affect honeybee learning, while oxytetracycline slows the onset of foraging in managed colonies. 

For the current paper, the researchers conducted lab experiments with managed bumblebees, Bombus impatiens, to test the effects of an upper-limit dietary exposure to streptomycin. Half of the bees were fed on plain sucrose, or sugar water, to simulate nectar. The remaining bees were fed on sucrose dosed with streptomycin. 

After two days on this diet, the bees were presented different-colored cardboard strips — one yellow and the other blue. One color was saturated with plain water and the other was saturated with sucrose. In a series of training trials, each bee was presented a single, colored strip until it touched it with its antennae or proboscis. 

The researchers measured the number of trials it took for a bee to show a preference for the color strips saturated with sucrose. The bees fed streptomycin often required roughly three times as many trials to make the association, relative to the other bees. The antibiotic-treated bees were also more likely to display avoidance behavior towards either of the stimuli. 

Those bees that passed a training threshold were given a short-term memory test five minutes later. Each bee was presented with both of cardboard strips simultaneously and allowed to select one. The rate at which the bees dosed with streptomycin selected the sucrose reward was around 55 percent, while the untreated bees selected the sucrose at a rate of nearly 87 percent. 

To assess foraging ability, trials were conducted in a foraging chamber containing an experimental array of artificial flowers that dispensed sucrose or plain water. The flowers were either blue or yellow but were identical in size and shape. Each bee was outfitted with a tiny, ultra-lightweight radio frequency identifier “backpack” to monitor its movements among the artificial flowers, which were each equipped with a short-range antenna and tracking system. 

The computer-analyzed results showed that the antibiotic-exposed bees visited far fewer sucrose-rewarding flowers relative to the control bees. 

In the spring, Avila and Brosi will launch field studies to determine if broadcast spraying of streptomycin affects bumblebees in pear orchards. 

“I was surprised at how strong an effect we found of streptomycin on bumblebees in the laboratory experiments,” Brosi says. “That makes it imperative to learn if we see similar effects in an agricultural setting.” 

The timing of antibiotic application, the amount applied and possible alternatives to the use of an antibiotic may be potential mitigation methods should the field research identify harmful impacts on bumblebees of agricultural spraying of streptomycin, the researchers note. 

Co-authors of the current study include Elizabeth Dunne, who did the work as an Emory environmental sciences major and has since graduated; and David Hofmann, a former post-doctoral fellow in Emory’s Department of Physics.

Related:

Pollinator extinctions alter structure of ecological networks

Evolutionary ecology could benefit beekeepers battling diseases

Wednesday, January 26, 2022

New approach in quest for cancer vaccines nets Emory chemist a Michelson Prize

"I love doing research and trying to solve problems to help people," says Rong Ma, shown receiving her PhD in chemistry at Emory in 2021. "Nothing can compare to the joy I get from doing science."

By Carol Clark

Emory chemist Rong Ma received a $150,000 Michelson Prize for her proposal to harness the mechanical processes of cells as a new approach in the long-running quest to develop cancer vaccines. Ma, who received her PhD from Emory in 2021, is a post-doctoral fellow in the lab of Khalid Salaita, Emory professor of chemistry. 

The Michelson Prizes: Next Generation Grants are annual awards to support young investigators who are “using disruptive concepts and inventive processes to significantly advance human immunology and vaccine and immunotherapy discovery research for major global diseases,” according to the Michelson Medical Research Foundation and the Human Vaccine Project, the organizations administering the awards. 

Ma was one of three scientists selected through a rigorous global competition to receive a 2021 Michelson Prize for immunotherapy research. 

“We need disruptive thinkers and doers who dare to change the trajectory of the world for the better,” says Gary Michelson, founder and co-chair of the Michelson Medical Research Foundation. “Yet promising young researchers too often lack the opportunities, resources and freedom to explore their bold ideas. The pandemic has created additional roadblocks for many of them. With the Michelson Prizes, we aim to provide early-career investigators a vital boost for their forward-thinking approaches.” 

“Rong Ma is a spectacular, highly motivated scientist,” Salaita says. “Sometimes I will tell her that a goal she sets it too lofty or difficult to pull off, but she will look back at me and say, ‘I want to do really big, difficult things.’” 

“To find specific antigens on cancer cells for cancer vaccine development is extremely challenging, partly because of the ambiguity in predicting what antigens the body’s immune cells can recognize,” Ma says. “Many researchers are focused on using genetic sequencing techniques to find genetic mutations and predict tumor-specific antigens to achieve this goal.” 

Ma’s proposal, however, is to use the mechanical forces transmitted by immune cells to antigens as a marker to identify and evaluate whether an antigen can trigger a potent immune response. If the method works in a mouse-model system, Ma explains, the long-range vision would be to isolate the immune cells that are mechanically active when recognizing cancer-specific antigens. The identified antigens and isolated immune cells could then be used to train the body to defend against cancer cells. 

A love of complex systems 

As an undergraduate in her native China, Ma majored in environmental sciences. The interdisciplinary nature of environmental sciences taught her to think about complex problems from different perspectives and to integrate knowledge across specialties. 

During a masters’ program in environmental science and technology at City University in Hong Kong, Ma came across cancer research and decided to shift her focus to medicinal chemistry. “I love working on complex systems,” Ma says, “but I realized that I had a better chance of making a valuable contribution by focusing on a smaller-scale complex system, like the immune cells.” 

She was especially intrigued by research published in 2016 by the lab of Khalid Salaita, which specializes in the mechanical forces of cellular processes. The Emory researchers found that T cells, the security guards of the immune system, use a kind of mechanical “handshake” to test whether a cell they encounter is a friend or a foe. The lab had developed special tools to make this discovery — DNA-based tension sensors that light up, or fluoresce, in response to a minuscule mechanical force of a piconewton — about one million-millionth the weight of an apple. 

Ma came to Emory for her PhD in chemistry, so that she could work in the Salaita lab and help advance this technology. “At that point, it was a relatively new perspective to investigate the mechanical forces of cells and begin to understand these processes,” Ma says. “It opened up a whole new world of research for me.” 

Harnessing molecular forces 

The Salaita lab has continued to develop the tension sensors and further observe and characterize the mechanical forces of T cells. “We’ve advanced our understanding to the point where we can start exploring how to harness the molecular forces in cells for mechanically triggered therapeutics,” Ma says. 

T cells continuously patrol through the body in search of foreign invaders. They have molecules known as T-cell receptors (TCR) that can recognize specific antigenic peptides on the surface of a pathogenic or cancerous cell. When a T cell detects an antigen-presenting cell (APC), its TCR connects to a ligand on the APC. If the T cell determines the ligand is foreign, it becomes activated and starts a signaling chain to recruit other cells to come and help mount an immune response. 

The human body contains millions of different T cells and they specialize in recognizing specific antigenic peptides and binding with them. A current approach for research into cancer vaccines is to painstakingly try to identify which peptides are antigenic and which T cells are activated by them.

Studying the binding process in a laboratory solution, however, turns out not to be the most reliable method for pairing a cancer peptide with the T cell that it triggers. That’s because, in the body, cells are moving and sliding past each other’s surfaces. A T cell receptor needs to grab on to a cancer peptide and give a strong “handshake” in order for it to stick. 

“It turns out that testing the binding in solution is not the same as binding in more dynamic, real-world conditions,” Salaita explains. “Rong Ma has figured out a way to measure the duration of the binding ‘handshake tug’ at the interface of the cell and a glass slide presenting these antigens. We believe this method may be further developed into a much better way to determine which particular cancer peptides are going to trigger a response in which particular T cell, and even which T cell receptor is doing the tugging.” 

Testing the method 

In experiments, Ma will try to establish a proof-of-concept of this method. If it proves effective, then it may be possible to amplify those cancer-specific T cells and T cell receptors in a laboratory to help cancer immunotherapy development. The challenge of pairing the body’s millions of different T cell receptors with the billions of different antigens that may exist remains daunting. 

“Some of the preliminary data we have gathered looks promising, and the Michelson award will help us get the remaining data we need to test our method.” Ma says. “A cancer vaccine is the ultimate vision. We still have a long way to go to achieve that, but we hope that our method may provide another step forward.” 

This year’s Michelson Prize winners will receive their rewards in a virtual ceremony on March 10. “It is inspiring to see their passion for innovation and their courage to think out of the box,” says Wayne Koff, CEO and president of the Human Vaccines Project. “I look forward to their future breakthrough discoveries and how their research can contribute to the Human Vaccines Project’s mission of developing the first AI model of human immunity.”

Related:

T cells use 'handshakes' to sort friends from foes

Chemists reveal the force within you

Molecular beacons shine light on how cells 'crawl'

Wednesday, January 19, 2022

First genome-wide ancient human DNA from Sudan shines new light on Nile Valley past

"Ancient DNA is difficult to recover from areas that are extremely hot, because DNA tends to degrade in heat," says Kendra Sirak, shown in 2017 when she was an Emory PhD student of anthropology. While still a student, she began developing new techniques for extracting ancient DNA samples that are opening new vistas into the human past.

By Carol Clark

The first genome-wide, ancient human DNA data from Sudan reveals new insights into the ancestry and social organization of people who lived more than 1,000 years ago in the Nile Valley, an important genetic and cultural crossroads. 

Nature Communications published the analyses of the DNA of 66 individuals from a site in ancient Nubia known as Kulubnarti, located on the Nile River in Sudan, just south of the Egyptian border. 

“Before this work, there were only three ancient genome-wide samples available, from Egypt, for the entire Nile Valley,” says first author Kendra Sirak, who began the project as a PhD student at Emory University. “And yet the region was, and still is, an incredibly important part of the world in terms of the movement, meeting and mixing of people.” 

Sirak was the last graduate student of the late George Armelagos, former professor of anthropology at Emory and a pioneer in bridging the disciplines of archeology and biology. While still a graduate student in the 1960s, Armelagos was part of a team that excavated ancient skeletons from Sudanese Nubia, so the bones would not be lost forever when the Nile was dammed. 

“Nubia was a place of human habitation for tens of thousands of years,” says Sirak, who is now a staff scientist at Harvard University. “This ancient genetic data helps fill in some major gaps in our understanding of who these people were.” 

The 66 individuals date back from 1,080 to 1,320 years ago, during the Christian Period of Sudanese Nubia, prior to the genetic and cultural changes that occurred along with the introduction of Islam. The analyses showed how the Kulubnarti gene pool formed over the course of a least a millennium through multiple waves of admixture, some local and some from distant places. They had ancestry seen today in some populations of Sudan, as well as ancestry that was ultimately West Eurasian in origin and likely introduced into Nubia through Egypt. 

“A key finding is that social status did not have a strong relationship to biological relatedness or to ancestry in this ancient population, who lived during a period of cultural and social change,” says Jessica Thompson, a co-senior author of the paper. Thompson, a former PhD supervisor of Sirak in Emory’s Department of Anthropology, is now at Yale University. 


During a field visit, Sirak took the above photo of a sunrise on the Nile River. The Nile Valley region "was, and still is, an incredibly important part of the world in terms of movement, meeting and mixing of people," she says.

The remains of the individuals came from two cemeteries with Christian-style burials that previous evidence indicated were socially stratified. In one cemetery, located on an island in the Nile, the skeletal remains bore more markers of stress, disease and malnutrition and the average age of those buried was just over 10 years old. By contrast, the average age at death in the other cemetery, located on the mainland, was 18 years. 

One hypothesis that grew out of this skeletal evidence was that the island cemetery was for a Kulubnarti “underclass,” possibly laborers for members of landowning families buried in the mainland cemetery. It was a mystery whether the social stratification may have developed because one population came from a different origin. 

A genome-wide analysis suggests that was not the case — the people buried in the separate cemeteries came from a single genetic population. 

“It seems that people in this area did not use biological ancestry as a basis for social differentiation,” Thompson says. “This reinforces the point that dividing people up socially on the basis of their genetic ancestry is a recent phenomenon, with no basis in universal human tendences.” 

Another key finding of the genetic analyses shows that some people as close as second-degree relatives were buried across the cemetery divide. Examples of second-degree relationships include grandparents to grandchildren, aunts and uncles to nieces and nephews, and half siblings. 

“That indicates that there was some fluidity among the two groups of people,” Sirak says. “There wasn’t an intergenerational caste system that meant someone was prescribed to being in the same social group as all of their relatives.” 

A further interesting twist is that much of the Eurasian-derived ancestry within the population came from women. “Often when you think of ancestry and how genes move, you think of males who are trading or conquering or spreading religion,” Sirak says. “But the genetic data here reveals that female mobility was really crucial to shaping the gene pool in Kulubnarti.” 

One possible explanation is that Kulubnarti was a patrilocal system, meaning that males tended to stay where they were born and females moved away from their homelands. 

“The Christian Period Nubians from Kulubnarti are fascinating,” Sirak says. “They survived in a barren, isolated, desolate region where life was never easy. I like to think that the ancient DNA research is giving a new life to these people from 1,000 years ago by providing a more nuanced view of them. Anytime you’re studying someone’s remains, their physical being, you owe it to them to tell the most accurate, respectful and meaningful story that you can.” 

The late George Armelagos during the 1980s. He and fellow faculty members built Emory's Department of Anthropology into a powerhouse of the biocultural approach to the field.

Sirak came to Emory as a graduate student in 2012 to study human bones and paleopathology under Armelagos. By that time, he and fellow faculty members had built Emory’s Department of Anthropology into a powerhouse of the biocultural approach to the field. In particular, Armelagos, his colleagues and graduate students studied the remains of the Sudanese Nubians to learn about patterns of health, illness and death in the past. 

A long missing piece in the studies of this population, however, was genetic analysis. So, in 2013, Armelagos sent Sirak to one of the best ancient DNA labs in the world, University College Dublin, with samples of the Nubian bones. 

“I had no interest in genetics,” Sirak recalls, “but George was a visionary who believed that DNA was going to become a critical part of anthropological research.” 

Sirak soon became hooked when she saw how she could combine her interest in ancient bones with insights from DNA. She formed collaborations not just in Dublin but at Harvard Medical School’s Department of Genetics and elsewhere, investigating mysteries surrounding deaths going back anywhere from decades to ancient times. 

Armelagos was 77 and still mentoring Sirak, his last graduate student, when he died of pancreatic cancer in 2014. Dennis Van Gerven, an emeritus professor of anthropology at the University of Colorado at Boulder, took over Sirak’s mentorship, along with Thompson. Van Gerven was among Armelagos’ first group of students, and he also spent decades studying the Sudanese Nubians. 

Sirak stuck with her PhD dissertation project of trying to collect enough ancient DNA from the Nubian remains for analysis. 

“Ancient DNA is difficult to recover from areas that are extremely hot, because DNA tends to degrade in heat,” she explains. 

Genetic sequencing techniques kept improving, however, and Sirak was working at the forefront of the effort. In 2015, while still an Emory graduate student, she was among the researchers who realized that a particular part of the petrous bone consistently yielded the most DNA. This pyramid-shaped bone houses several parts of the inner ear related to hearing and balance. In addition, Sirak developed a technique to drill into a skull and reach this particular part of the petrous bone in the most non-invasive way possible, while also getting enough bone powder for DNA analysis. The use of this part of the petrous bone is now the gold standard in ancient DNA analysis. 

In 2018, Sirak received her PhD from Emory and went on to work in the lab of David Reich, a geneticist at Harvard Medical School who specializes in the population genetics of ancient humans. 

She and her colleagues continued to push the boundaries of what’s possible with ancient DNA sequencing. They managed to get whole-genome samples from the petrous bones of 66 of the Sudanese Nubians, ushering in a whole new era of bioarchaeology for the Nile Valley. “I don’t think we would have succeeded in this work had we not known to focus on the specific part of the petrous bone,” Sirak says. 

“It’s incredible to me that George asked me to focus on ancient DNA back in 2012, long before these techniques were developed,” she adds. “He had a way of making anyone who was working with him really feel important and powerful and that gave me the confidence to strike out on a pioneering path.”

“George Armelagos’ influence is everywhere,” adds Thompson, explaining that he also advised many senior people who mentored her early in her career. 

Funded by National Geographic Explorer grants, Sirak is now working with Sudanese colleagues to gather and analyze ancient DNA samples from other geographic locations in the Nile Valley, going even deeper into its past, to add more details to the story of how people moved, mixed and thrived in the region across millennia. 

As the last graduate student of Armelagos — and then a mentee of Van Gerven, one of Armelagos’ first students — Sirak feels like she is completing a circle. The publication of the current paper is the realization of Armelagos’ last wishes for the project. 

“It’s really special for me to be able to use ancient DNA to build on decades of anthropological and archeological research for the region,” Sirak says. “I know that George would be proud and thrilled. I’m part of this amazing lineage of researchers now. And the desire to continue what they started is a huge motivation for me.” 

In addition to Reich, Thompson and Van Gerven, senior authors of the Nature Communications paper include Nick Patterson (Broad Institute of Harvard and MIT) and Ron Pinhasi (University College, Dublin). Co-authors include researchers from these institutions as well as the University of Vienna, the University of Coimbra in Portugal, the Howard Hughes Medical Institute, the University of Pompeu Fabra in Barcelona, the University of Georgia, the University of California, Santa Cruz, and the University of Michigan.

Related:

Emory students help unravel prehistoric mysteries

Malawi yields oldest-known DNA from Africa

Pioneering techniques in anthropological genetics

Ancient DNA lab maps little-explored human lineages