Research Now - Summer 2021
New Antibiotic Clears Multidrug-Resistant Gonorrhea in Mice
By Gail McCormick
A new antibiotic compound clears infection of multidrug-resistant gonorrhea in mice in a single oral dose. The compound targets a molecular pathway found in bacteria but not humans, called the trans-translation pathway, and could lead to new treatments for gonorrhea and infections from other bacteria, such as tuberculosis and MRSA.
“In this paper, we provide a proof of concept that inhibiting the trans-translation pathway can effectively clear multidrug-resistant gonorrhea in animals,” said Ken Keiler, professor of biochemistry and molecular biology.
The researchers previously identified a promising trans-translation inhibitor that clears gonorrhea infection in lab cultures. In this study, members of the research team strategically altered the compound so it is viable for use in humans. Then they tested one of the modified compounds in mice infected with a strain of gonorrhea that is resistant to almost all approved antibiotics. A single oral dose of the compound completely cleared the infection in 80 percent of mice within six days, and the bacterial load in the remaining 20 percent was dramatically reduced.
“In some cases, bacteria can develop resistance to a drug when additional doses are skipped,” said Keiler. “With a single dose therapy, a patient could complete the treatment during a visit to their health provider.”
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Quantum Insulators Create Multilane Highways for Electrons
By Gail McCormick
New multilayered quantum insulators could lead to increased speed and efficiency of information transfer in electronic devices, without energy loss.
In most metals used in electronic devices, increasing the number of electrons to improve efficiency of electron flow can cause a sort of traffic jam because electrons moving in different directions repel each other and scatter. But in quantum anomalous Hall (QAH) insulators, electron flow is constrained to the edges, with electrons on each edge going in opposite directions, “like splitting a road into a two-lane highway,” said Cui-Zu Chang, assistant professor of physics.
QAH insulators are created in a material called a topological insulator—a thin layer of film with a thickness of only a couple dozen atoms—that have been made magnetic and theoretically do not lose any energy as heat.
“This unique property makes QAH insulators a good candidate for use in quantum computers and other small, fast electronic devices,” said Chao-Xing Liu, associate professor of physics.
In prior studies, the QAH effect had been experimentally realized only in materials with essentially a single two-lane highway for electrons. In this study, the researchers stacked alternating layers of magnetic and nonmagnetic topological insulators, essentially constructing five parallel highways for electrons.
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Mapping the Local Cosmic Web
By Gail McCormick
Dark matter provides the skeleton for what cosmologists call the cosmic web, the large-scale structure of the universe that, due to its gravitational influence, dictates the motion of galaxies and other cosmic material. However, the distribution of dark matter in the local universe is currently unknown because it cannot be measured directly. Researchers must instead infer its distribution based on its gravitational influence on other objects in the universe, like galaxies.
An international research team used machine learning to build a model that uses information about the distribution and motion of galaxies to predict the distribution of dark matter. The resulting map of the local cosmic web successively reproduced known prominent structures in the local universe and identified several new structures that require further investigation, including smaller filamentary structures that connect galaxies.
“Having a local map of the cosmic web opens up a new chapter of cosmological study,” said Donghui Jeong, associate professor of astronomy and astrophysics.
The distribution of dark matter can now be related to other emission data to investigate the nature of dark matter. The model can also be evolved forward or backward in time to better understand the fate and history of our cosmic neighborhood.
The Muon’s Magnetic Moment Fits Just Fine
By Sam Sholtis
A new calculation of the strength of the magnetic field around the muon—a subatomic particle similar to an electron—closes the gap between theory and experimental measurements, bringing it in line with the standard model that has guided particle physics for decades.
Twenty years ago, physicists detected what seemed to be a discrepancy between measurements of the muon’s “magnetic moment”—the strength of its magnetic field—and theoretical calculations of what that measurement should be, raising the tantalizing possibility of physical particles or forces as yet undiscovered.
“We can predict the properties of particles extremely precisely based on theory alone, so when theory and experiment don’t match up, we can get excited that we might have found something new, something beyond the standard model,” said Zoltan Fodor, professor of physics.
The new calculations bring theory back in line with measurement.
“If our calculations are correct, it appears that we don’t need any new physics to explain the muon’s magnetic moment—it follows the rules of the standard model,” said Fodor. “Although the prospect of new physics is always enticing, it’s also exciting to see theory and experiment align. It demonstrates the depth of our understanding and opens up new opportunities for exploration.”
Unusual DNA Folding Increases the Rates of Mutations
By Sam Sholtis
DNA sequences that can fold into shapes other than the classic double helix tend to have higher mutation rates and play a major role in determining regional variation in mutation rates across the human genome. Deciphering the patterns and causes of this variation is important for understanding evolution and for predicting sites of new mutations that could lead to disease.
“Most of the time we think about DNA as the classic double helix; this basic form is referred to as B-DNA,” said Wilfried Guiblet, a graduate student. “But as much as 13 percent of the human genome can fold into different conformations called non-B DNA.”
“To identify differences in mutation rates between B- and non-B DNA we used statistical tools from functional data analysis, in which we compare the data as curves rather than looking at individual data points,” said Marzia A. Cremona, a postdoctoral researcher.
For most types of non-B DNA, the team found increased mutation rates.
“We’ve been studying regional variation in mutation rates for a long time from a lot of different angles,” said Francesca Chiaromonte, Huck Chair in Statistics for the Life Sciences. “The fact that non-B DNA is such a major contributor to this variation is an important discovery.”
Did Early Life Need Long, Complex Molecules to Make Cell-Like Compartments?
By Sam Sholtis
Protocell compartments used as models for an important step in the early evolution of life on Earth can be made from short polymers.
“We wanted to know if we could make compartments that could function like protocells out of molecules of a size that would have been available on Earth when life was beginning,” said Christine Keating, Distinguished Professor of Chemistry.
The researchers created the compartments by combining two oppositely charged polymers in a solution. “We tested a large number of combinations of polymers types and lengths to try to establish the parameters for compartment formation,” said graduate student Fatma Pir Cakmak.
“Life could have formed in the ocean, in brackish water, or in freshwater,” said graduate student Saehyun Choi. “The compartments were stable in salt concentrations high enough to suggest that they are a relevant model for any of these situations.”
The compartments also were able to sequester the RNA. “RNA formed much of its secondary structure but did not maintain its fully native folding inside the compartments,” said graduate student McCauley O. Meyer.
“What we’re after is not the precise transcript of what happened on Earth billions of years ago,” said Phil Bevilacqua, Distinguished Professor of Chemistry and of Biochemistry and Molecular Biology. “Instead, we want to know how feasible it is for life to start.”
The Three Rs of the Genome: Reading, Writing, and Regulating
By Sam Sholtis
A massive effort to map the precise binding locations of over 400 proteins on the yeast genome has produced the most thorough and high-resolution map of chromosome architecture and gene regulation to date.
The team used a technique called ChIP-exo to precisely and reproducibly map the binding locations of proteins that interact with the yeast genome. They performed over 1,200 individual experiments producing billions of individual points of data.
“The resolution and completeness of the data allowed us to identify 21 protein assemblages and also to identify the absence of specific regulatory control signals at housekeeping genes,” said Shaun Mahony, assistant professor of biochemistry and molecular biology. “The computational methods that we’ve developed to analyze this data could serve as a jumping off point for further development for gene regulatory studies in more complex organisms.”
“We were surprised to find that housekeeping genes lacked a protein-DNA architecture that would allow specific transcription factors to bind, which is the hallmark of inducible genes,” said B. Franklin Pugh, a professor at Cornell University who started the project when he was at Penn State. “Whether or not this pattern holds up in multicellular organisms like humans is yet to be seen.”