Wednesday, July 26, 2023

Merck Prize boosts work on air sensor for pandemic pathogens

"There is a need for viral-detecting devices for public indoor air spaces as we enter an era when pandemics will likely become more common," says Emory chemist Khalid Salaita.

Merck KGaA, Darmstadt, Germany, awarded its 2023 Future Insight Prize to Khalid Salaita, professor of chemistry at Emory University. The award comes with $540,000 to fund the next phase of research into an air sensor that can continuously monitor indoor spaces for pathogens that can cause pandemics. 

“I’m extremely thankful to receive the Future Insight Prize as this enables us to continue our path toward an early-warning system for emerging threats,” Salaita says. “Our research sets the stage for fully automated detection of airborne pathogens without human intervention or sample processing.” 

The Merck Future Insight Prize recognizes groundbreaking ideas to solve some of the world’s most pressing challenges in health, nutrition and energy. 

The Salaita lab’s sensor, a rolling micro-motor called “Rolosense,” holds the potential to help mitigate, or even prevent, a pandemic. 

Read the full story here.

Tuesday, July 18, 2023

Biophysicists reveal how three proteins interact to fine-tune cellular movement

Graduate student Heidi Ulrichs created this cartoon to illustrate previous theories that three enzymes could not all "dance" together on the end of an actin filament. The filament (in blue) is shown with the enzymes, in pink, gold and green, engaged in a kind of "sibling rivalry." The Emory physicists discovered that, in fact, the three enzymes could simultaneously work together on the end of an actin filament.
 

By Carol Clark

A single human cell teems with as many 100,000 different proteins. Actin is one of the most abundant and essential of them all. This protein forms into filaments that help make up the skeleton of cells, giving them shape. And as the actin filaments elongate, they work like muscles, pushing against the inner membrane of a cell to move it forward. 

Three other proteins are known to drive the activities of actin. One class of protein assembles individual actin molecules into actin filaments, another causes the filaments to stop growing and a third disassembles filaments. 

Biophysicists at Emory University, however, have discovered an even more complex and nuanced view of how these three proteins together influence actin dynamics. Nature Communications published the findings, showing how these proteins sometimes shift from solo or duet acts to perform as a trio, allowing them to fine-tune the activity of actin filaments. 

The discovery opens another window onto the dynamics of cellular movement, which is key to processes ranging from stem-cell differentiation and wound healing to the development of diseases such as cancer. 

“We found that while these three proteins do one thing when working on their own, they do a completely different thing when the other two proteins join them,” says Shashank Shekhar, Emory assistant professor of physics and cell biology, and senior author of the study. “It gets really complex, very fast.” 

“No one had looked at all of these proteins interacting at once on actin,” adds Heidi Ulrichs, co-first author of the study and an Emory PhD candidate in biochemistry, cell and developmental biology. “Our paper is the first report of all three of them occupying the same barbed end of an actin filament.” 

Ulrichs worked closely on the project with Ignas Gaska, a postdoctoral fellow in the Shekkhar lab who is co-first author of the paper. 

Building on previous research 

Research into how proteins act individually on actin is relatively well-characterized. 

A polymerase protein, such as formin, drives elongation of actin. Formin positions itself at the end of an actin filament, grabs onto free-floating actin molecules and stacks them up one by one to keep growing the end. 

Depolymerase proteins, such as twinfilin, are another class of proteins that influence actin. Twinfilin works like a lint roller, binding to the end of a filament and peeling away one molecule at a time. Twinfilin can repeat the process to disassemble the actin filament entirely. 

Proteins known as cappers can stop the elongation and disassembling of the filaments. A capper attaches to the end of an actin filament and covers it like a hat, blocking activity by the other proteins. 

This knowledge was built up by isolating one protein at a time to study how it influences actin. More recent studies have also shown simultaneous interactions between twinfilin and capping proteins. 

A new approach using advanced technology 

For the current study, the researchers wanted to explore whether formin, twinfilin and the capping protein could all three act simultaneously on actin. 

“An actin filament end is really tiny, just five nanometers across,” Shekhar explains. “One thought was that there just isn’t enough real estate available for three proteins to work on a single actin filament at once.” 

The Shekhar lab is one of only a handful in the world using the highly specialized technique of microfluidics-assisted total internal reflection fluorescence microscopy (mf-TIRF) to study how the actin cytoskeleton remodels itself. 

Cells are packed with thousands of proteins moving around, performing different functions, making it impossible to track all of them. Researchers must isolate the proteins of interest and study them outside of a cellular system, by introducing them to a microfluidic system on a microscope slide. 

The mf-TIRF technology allows the Shekhar Lab to attach fluorescent orbs to single protein molecules so that researchers can better observe what these molecules are doing through a microscope. 

In experiments, the researchers tagged molecules of actin, formin, twinfilin and the capping protein with four different colors that emitted fluorescent light. They then introduced actin to the microfluidic system and added the other proteins one at a time. 

Establishing a new paradigm 

The results startled them. 

When twinfilin, the protein that breaks apart an actin filament, was added in the presence of both formin and the capping protein, twinfilin actually worked to speed up the process of filament elongation. 

“That’s counterintuitive, which is cool,” Ulrichs says. “Doing science you get surprised all the time.” 

Twinfilin alone could not join formin on the end of the actin filament. However, when the capping protein was also present, all three could simultaneously work together on the tiny surface of the actin filament. 

Shekhar compares the effects of all three proteins working together to a knob that allows for more precise control of a process. 

“Our findings establish a new paradigm in which the three proteins work in concert to fine-tune how fast or slowly actin filaments are formed,” he says. The dynamics of how the three proteins interact with actin is fundamental to teasing apart the complex mysteries of how cells function normally and what happens when something goes wrong. 

“We’re building up knowledge, step by step, study by study, on the dynamics of what’s happening inside of a cell,” Ulrichs says. 

Related:

How protein assemblies drive cell movement 

'Firefly' imaging zooms in on the forces within us

Tuesday, July 11, 2023

A medical entomologist battles bubonic plague in Madagascar

"There are 48 different species of fleas in Madagascar, but only a handful of them are found in a human environment," says Adelaide Miarinjara, an expert in the ecology of plague transmission.

Madagascar is famous for its biodiversity and unique wildlife, especially lemurs. Less well known is that it’s a hot spot for bubonic plague. The island nation off the southeast coast of Africa is one of the last places where large outbreaks of human plague happen regularly. 

Adelaide Miarinjara, who grew up in Madagascar, is now a medical entomologist and a postdoctoral fellow at Emory. Her project, unraveling some of the many mysteries surrounding plague, spans the lab of Thomas Gillespie, Emory professor of environmental sciences, and the Pasteur Institute. 

“I chose not to study lemurs,” Miarinjara says. “So many people are already doing that. The animals that I work with, rats and fleas, are not nearly as charismatic. But learning about them may lead to better policies to prevent people getting plague.” 

“As a microbiologist, Adelaide is extremely creative,” Gillespie says. “She’s developed whole new protocols for studying fleas that are allowing her to zero in on unanswered questions.”

Read more about her work here.

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Valuing Natural Capital Vital to Avoid the Next Pandemic

Monday, July 10, 2023

New book eyes Earth's excavators, from microbes to elephants and dinosaurs

Anthony Martin in Emory's Lullwater Forest with the trunk of a pine tree carved up by beetles. Some species of beetles chew through wood to create tunnels where they lay their eggs. (Photo by Ruth Schowalter)

The ordinary person looks at Stone Mountain and sees a solid, unmovable monolith. Emory paleontologist Anthony Martin, who thinks in geologic time, sees something more akin to a giant sugar cube. 

Ever since the crystalized mass of igneous-born minerals rose from deep underground, pushed by the upwelling of magma that formed the Blue Ridge Mountains around 350 million years ago, the giant rock’s flanks have faced continuous assault — and not just from weather and water. 

Stone Mountain “is fighting a battle against life, and life is winning,” Martin writes in the preface of his new book, “Life Sculpted: Tales of the Animals, Plants and Fungi That Drill, Break and Scrape to Shape the Earth.” 

The University of Chicago Press recently published “Life Sculpted," marking the fifth book during the past 10 years by Martin, professor of practice in Emory’s Department of Environmental Sciences. 

Read more here. 

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Monday, May 15, 2023

'Love hormone' guides young songbirds in choice of 'voice coach'

Zebra finches are highly social birds and will press a lever in order to hear a recording of another Zebra finch singing. (Photo by Carlos Rodríguez-Saltos)

By Carol Clark

Oxytocin, the so-called “love hormone,” plays a key role in the process of how a young zebra finch learns to sing by imitating its elders, suggests a new study by neuroscientists at Emory University. Scientific Reports published the findings, which add to the understanding of the neurochemistry of social learning. 

“We found that the oxytocin system is involved from an early age in male zebra finches learning song,” says Natalie Pilgeram, first author of the study and an Emory PhD candidate in psychology. “It’s basic science that may lead to insights into the process of vocal learning across the animal kingdom, including humans.” 

“Our results suggest that the neurochemistry of early social bonds, particularly during language learning, may be relevant in studies of autism,” adds Donna Maney, a professor of neuroscience in Emory’s Department of Psychology and senior author of the study. 

Young male zebra finches learn to sing by listening to an adult male tutor that they choose to pay close attention to, normally their biological father or a “foster” father who nurtures them. This social process holds some similarities for how children learn to speak, making the birds a laboratory model for the neural underpinnings of social vocal learning. 

In the current paper, the researchers show how oxytocin, a hormone essential to social bonding, influences young finches exposed only to the songs of unfamiliar males. In experiments, blocking the young birds’ oxytocin receptors while they listened to a male biased the birds against that male’s song. Instead they preferred to listen to and eventually learn the song of a male they heard when their oxytocin receptors were allowed to function normally. 

The paper builds on previous work by the Maney lab regarding the hormonal and genetic influences on social behavior. Her lab is working with researchers at the Marcus Autism Center in Atlanta to maximize any potential translational impact of its research findings. 

Finding their voice 

Zebra finches are highly social birds. In the wild they nest together in large colonies. Only adult males sing, primarily to court females. 

From the time they hatch, the males begin listening for song, and memorizing particular songs, even before they can actually sing one. “Up until around day 50, they are making little cheeps and warbles, what we call ‘subsong,’” Pilgeram explains. “It’s similar to human infants who begin to babble at around six months without actually talking.” 

During this sensitive listening phase, a male zebra finch pays closest attention to the song of its father, even though it can hear other adult males nearby. 

In a laboratory environment, research shows that if a biological father is removed from a cage before a male hatches and then substituted with a “foster father” that they can interact with, the young male will prefer the song of the foster father over other males it can hear. The young males demonstrate this preference by pressing levers that allow them to hear playback of different songs. 

Learning from their environment 

“The young birds have got to learn all that they can from their environment,” Pilgeram says. “Just as during human development, the birds pay the closest attention to their immediate caregivers, on whom they rely for everything.” 

Around day 50, the young male finches enter puberty and what is called the “plastic song phase.” During this time, they practice their song motor skills and actively try to produce song. Although they begin to shift their attention away from their fathers and show a preference for hearing songs of other males, each young male still practices dad’s tune. 

By day 100, most male zebra finches are fully singing their father’s song. They have reached adulthood and their tune has “crystalized” into the song that they will sing for the rest of their lives. 

In previous research, the Maney lab found that the stronger the preference a male zebra finch shows for its father’s song during the early listening phase, the more closely its crystalized adult song will mimic that of the father. 

The role of oxytocin 

For the current paper, the researchers wanted to test whether the oxytocin system played a role in that preference. 

The research centered on male juvenile zebra finches hatched in the lab. At day four, the fathers were removed from each of the youngsters’ cages so they were raised only by their mothers. The cages were enclosed in chambers that prevented the young birds from hearing song from other birds housed nearby. 

Beginning at day 27 in a young bird’s life, it was exposed to a series of tutoring sessions by two different adult male tutors that it had never heard. The tutor’s cage was placed next to the cage of the young bird, or pupil. When it was exposed to one of the tutors, the pupil was given a substance that blocked its oxytocin receptors from activating. When the young bird was exposed to the other tutor it received a control substance that allowed its oxytocin receptors to function normally. 

After completing a series of tutoring sessions, the pupils were presented with two different levers they could press in their cages. Pressing one lever was more likely to play the song they heard when their oxytocin receptors were blocked. The other lever was more likely to play the song they heard with normally functioning oxytocin. 

The results showed that early in their development, the juveniles favored the song that they heard when their oxytocin was not blocked. 

Building on past findings 

“We also found that when their oxytocin was not blocked, the birds’ developmental milestones fit the same data curve as in our previous research,” Maney says. “They showed an early preference for the song of one tutor, then switched to preferring the other song during puberty.” 

The preference flattened out as they began singing the song of their chosen tutor, she adds. And the stronger the preference that they showed for the chosen tutor’s song during the early listening phase, the more closely their own adult song resembled that of the chosen tutor. 

The researchers also noted behavioral differences in the way the pupils and tutors interacted. With normally functioning oxytocin, a pupil pecked more often at the wall of its cage facing the tutor and more often preened in a fashion known to be associated with focused listening in the birds, compared to when its oxytocin was blocked. 

“Our results suggest that the oxytocin system is involved in how an animal decides where to focus its attention very early in its life,” Pilgeram says. 

Co-authors of the study include Carlos Rodríguez-Saltos, who received his doctorate from Emory and is now at Illinois State University; postdoctoral fellow Nicole Baran; research technicians Matthew Davis and Erik Iverson; and Emory undergraduates Sumin Lee, Emily Kim and Aditya Bhise. 

The work was funded by the National Science Foundation and the Silvio O. Conte Center for Oxytocin and Social Cognition. 

Related:

How a single gene drives aggression in songbirds 

Songbird data yields new theory for learning sensorimotor skills