Contact/News Media
Friday, August 25, 2023
Buffalo slaughter left lasting impact on Indigenous peoples
Wednesday, August 23, 2023
Biologist gets the scoop on squash bug poop
By Carol Clark
The squash bug carries a gut bacterium that is essential for the bug’s development into an adult. But when they hatch from their eggs, squash bug nymphs do not have the bacteria in their systems. That left scientists who study the interplay between insects and their internal microbes wondering: How do the nymphs acquire these essential microbes?
Jason Chen, an Emory University graduate student in the Department of Biology, stumbled upon a clue one evening in the lab.
He had finished up experiments on some adult squash bugs whose Caballeronia bacteria he had tagged with a red fluorescent protein. The bugs were housed in a plastic box with pieces of paper towel inside as bedding. He tossed some nymphs inside the container just as a place to hold them while he cleaned up for the day.
“When I came back to turn the lights out, I noticed that all the nymphs had flocked around one of the poop spots left on a paper towel by the adults,” Chen says. “Normally nymphs wander around a lot but they had all stopped around this poop. They were transfixed by it. I wondered what that behavior meant.”
He eventually checked the nymphs under a microscope and saw that their guts lit up with the same red fluorescence as the adults. More experiments confirmed the finding — nymph squash bugs eat the feces of adults to acquire the bacteria they need to grow.
Current Biology published the discovery, which may offer insights for improved methods to control the squash bug, a significant agricultural pest.
Read more about the discovery here.
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Thursday, August 10, 2023
Images of enzyme in action reveal secrets of antibiotic-resistant bacteria
By Carol Clark
Bacteria draw from an arsenal of weapons to combat the drugs intended to kill them. Among the most prevalent of these weapons are ribosome-modifying enzymes. These enzymes are growing increasingly common, appearing worldwide in clinical samples in a range of drug-resistant bacteria.
Now scientists have captured the first images of one important class of these enzymes in action. The images show how the enzymes latch onto a particular site on the bacterial ribosome and squeeze it like a pair of tweezers to extract an RNA nucleotide and alter it.
The Proceedings of the National Academy of Sciences (PNAS) published the findings, led by scientists at Emory University. The advanced technique of cryoelectron microscopy made the ultra-high-resolution, three-dimensional snapshots possible.
“Seeing is believing,” says Christine Dunham, Emory professor of chemistry and co-corresponding author of the paper. “The minute you see biological structures interacting in real life at the atomic level it’s like solving a jigsaw puzzle. You see how everything fits together and you get a clearer idea of how things work.”
The insights may lead to the design of new antibiotic therapies to inhibit the drug-resistance activities of RNA methyltransferase enzymes. These enzymes transfer a small hydrocarbon known as a methyl group from one molecule to another, a process known as methylation.
“Methylation is one of the smallest chemical modifications in biology,” says Graeme Conn, professor of biochemistry in Emory’s School of Medicine and co-corresponding author of the paper. “But this tiny modification can fundamentally change biology. In this case, it confers resistance that allows bacteria to evade an entire class of antibiotics.”
Both Conn and Dunham are also members of the Emory Antibiotic Resistance Center.
First author of the paper is Pooja Srinivas, who did the work as a PhD candidate in Emory’s graduate program in molecular and systems pharmacology. She has since graduated and is now a postdoctoral fellow at the University of Washington.
Understanding the ribosome
Dunham is a leading expert on the ribosome — an elaborate structure that operates like a factory within a cell to manufacture proteins. Proteins are the machines that make cells run while nucleic acids such as DNA and RNA store the blueprints for life. The ribosome is made mostly of RNA, which does not just store information but can also act as an enzyme, catalyzing chemical reactions.
One goal of Dunham’s lab is to find ways to manipulate bacterial ribosomes to make them more susceptible to antimicrobials. If an antimicrobial successfully inactivates bacterial ribosomes, that shuts down the manufacturing of proteins essential for bacterial growth and survival.
The idea is to exploit differences in human cellular ribosomes and bacterial ribosomes, so that only the bacteria is targeted by an antimicrobial drug.
Antimicrobials, however, need to get past bacterial defenses.
“It’s like a molecular arms race,” Dunham explains. Bacteria keep evolving new weapons as a defense against drugs, while scientists evolve new strategies to disarm bacteria.
Enzymes that modify the ribosome
Conn is a leading expert in the bacterial defense weapons known as ribosomal RNA methyltransferase enzymes. This family of enzymes was originally discovered in soil bacteria. They are now increasingly found in bacterial infections in people and animals, making these infections harder to treat.
“They keep turning up more and more often in clinical samples of some nasty bacterial pathogens in different parts of the world,” Conn says.
The enzymes can drive deadly drug-resistance in pathogens such as E. coli, Salmonella, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacteriaceae. The enzymes add a methyl group at a specific site on the bacterial ribosome. That addition blocks the ability of a class of antibiotics known as aminoglycosides to bind and cause their antibacterial action.
For the PNAS paper, the researchers focused on a culprit within this family of enzymes known as ribosomal RNA methyltransferase C, or RmtC.
A complicated enzyme
For decades, researchers have relied on a technique known as X-ray crystallography to reveal the atomic details of how molecular machines work when the molecules are arranged in a crystal.
In 2015, for example, Dunham’s lab obtained precise pictures through X-ray crystallography of how an enzyme known as HigB rips up RNA to inhibit growth of the bacteria. By restraining the growth of the bacteria that makes it, HigB establishes a dormant “persister cell” state that makes the bacteria tolerant to antibiotics.
The secrets of how the RmtC enzyme interacts with the ribosome, however, eluded X-ray crystallography.
“RmtC is much more complicated,” Dunham explains. “It’s an interesting enzyme from a basic science perspective because it looks so different from others.”
A resolution revolution
Recent advances in cryoelectron microscopy opened the door to zooming in on the complex mechanisms of RmtC.
Cryoelectron microscopy does not require crystallization to reveal the structures of molecules and how they interact. Instead, liquid samples are frozen rapidly to form a glassy matrix. The glassy matrix retains the three-dimensional structure of molecules and protects them from deterioration by the intense electron beam.
Meisam Nosrati, a former postdoctoral fellow in the Conn lab and a co-author of the PNAS paper, prepared samples of RmtC interacting with part of an E. coli ribosome. He tapped the expertise of co-author Lindsay Comstock, a chemist at Wake Forest University who developed a technique to trap and stabilize the enzyme in the needed position.
Nosrati then froze the samples on a tiny grid and sent them to the Pacific Northwest Center for Cryo-EM for imaging.
As a graduate student in the Dunham lab, Pooja Srinivas then analyzed and interpreted the microscopy dataset. She used computer algorithms to stitch together thousands of individual images.
The result turned the images into a flipbook that revealed the complicated structure of RmtC in action.
“The enzyme latches on like a pincer to the ribosome,” Dunham explains. “It tightens its grip until it squeezes out a nucleotide from the interior of an RNA helix. It then chemically modifies that nucleotide.”
The enzyme is exquisitely specific about where it binds to the ribosome, a huge macromolecule made up of 50 different proteins and 6,000 different RNA nucleotides.
The researchers used biochemistry techniques to validate that what they observed matched previous findings for how RmtC makes bacteria resistant to aminoglycoside antimicrobials that target the ribosome.
Strategies for new therapies
The researchers are now trying to develop new ways to counter the effects of RmtC and related enzymes based on the new information.
“Knowledge of the shape of the enzyme as its performs its chemical reaction gives us new targets to inhibit its effects,” Conn says. “For instance, we could target the pincer action of the enzyme to try to prevent it from squeezing and binding to the ribosome. We now know that the enzyme forms a pocket on its surface where a small molecule might sit to block this action.”
Additional co-authors of the PNAS paper are Natalia Zelinskaya and Debayan Dey, research scientists in the Conn lab. Funding for the work was provided by the National Institutes of Health and the Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease Award.
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Monday, August 7, 2023
Physicists open new path to exotic form of superconductivity
By Carol Clark
Physicists have identified a mechanism for the formation of oscillating superconductivity known as pair-density waves. Physical Review Letters published the discovery, which provides new insight into an unconventional superconductive state seen in certain materials, including high-temperature superconductors.
“We discovered that structures known as Van Hove singularities can produce modulating, oscillating states of superconductivity,” says Luiz Santos, assistant professor of physics at Emory University and senior author of the study. “Our work provides a new theoretical framework for understanding the emergence of this behavior, a phenomenon that is not well understood.”
First author of the study is Pedro Castro, an Emory physics graduate student. Co-authors include Daniel Shaffer, a postdoctoral fellow in the Santos group, and Yi-Ming Wu from Stanford University.
The work was funded by the U.S. Department of Energy’s Office of Basic Energy Sciences.
The puzzle of superconductivity
Santos is a theorist who specializes in condensed matter physics. He studies the interactions of quantum materials — tiny things such as atoms, photons and electrons — that don’t behave according to the laws of classical physics.
Superconductivity, or the ability of certain materials to conduct electricity without energy loss when cooled to a super-low temperature, is one example of intriguing quantum behavior. The phenomenon was discovered in 1911 when Dutch physicist Heike Kamerlingh Onnes showed that mercury lost its electrical resistance when cooled to 4 Kelvin or minus 371 degrees Fahrenheit. That’s about the temperature of Uranus, the coldest planet in the solar system.
It took scientists until 1957 to come up with an explanation for how and why superconductivity occurs. At normal temperatures, electrons roam more or less independently. They bump into other particles, causing them to shift speed and direction and dissipate energy. At low temperatures, however, electrons can organize into a new state of matter.
“They form pairs that are bound together into a collective state that behaves like a single entity,” Santos explains. “You can think of them like soldiers in an army. If they are moving in isolation they are easier to deflect. But when they are marching together in lockstep it’s much harder to destabilize them. This collective state carries current in a robust way.”
A holy grail of physics
Superconductivity holds huge potential. In theory, it could allow for electric current to move through wires without heating them up, or losing energy. These wires could then carry far more electricity, far more efficiently.
“One of the holy grails of physics is room-temperature superconductivity that is practical enough for everyday-living applications,” Santos says. “That breakthrough could change the shape of civilization.”
Many physicists and engineers are working on this frontline to revolutionize how electricity gets transferred.
Meanwhile, superconductivity has already found applications. Superconducting coils power electromagnets used in magnetic resonance imaging (MRI) machines for medical diagnostics. A handful of magnetic levitation trains are now operating in the world, built on superconducting magnets that are 10 times stronger than ordinary electromagnets. The magnets repel each other when the matching poles face each other, generating a magnetic field capable of levitating and propelling a train.
The Large Hadron Collider, a particle accelerator that scientists are using to research the fundamental structure of the universe, is another example of technology that runs through superconductivity.
Superconductivity continues to be discovered in more materials, including many that are superconductive at higher temperatures.
An accidental discovery
One focus of Santos’ research is how interactions between electrons can lead to forms of superconductivity that cannot be explained by the 1957 description of superconductivity. An example of this so-called exotic phenomenon is oscillating superconductivity, when the paired electrons dance in waves, changing amplitude.
In an unrelated project, Santos asked Castro to investigate specific properties of Van Hove singularities, structures where many electronic states become close in energy. Castro’s project revealed that the singularities appeared to have the right kind of physics to seed oscillating superconductivity.
That sparked Santos and his collaborators to delve deeper. They uncovered a mechanism that would allow these dancing-wave states of superconductivity to arise from Van Hove singularities.
“As theoretical physicists, we want to be able to predict and classify behavior to understand how nature works,” Santos says. “Then we can start to ask questions with technological relevance.”
Some high-temperature superconductors — which function at temperatures about three times as cold as a household freezer — have this dancing-wave behavior.
The discovery of how this behavior can emerge from Van Hove singularities provides a foundation for experimentalists to explore the realm of possibilities it presents.
“I doubt that Kamerlingh Onnes was thinking about levitation or particle accelerators when he discovered superconductivity,” Santos says. “But everything we learn about the world has potential applications.”
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