Unconventional quasiparticles predicted in conventional crystals (Science)

Posted on by Catherine Zandonella
Fermi arcs on the surface of uncoventional materials
Two electronic states known as Fermi arcs, localized on the surface of a material, stem out of the projection of a 3-fold degenerate bulk new fermion. This new fermion is a cousin of the Weyl fermion discovered last year in another class of topological semimetals. The new fermion has a spin-1, a reflection of the 3- fold degeneracy, unlike the spin-½ that the recently discovered Weyl fermions have.

By Staff

An international team of researchers has predicted the existence of several previously unknown types of quantum particles in materials. The particles — which belong to the class of particles known as fermions — can be distinguished by several intrinsic properties, such as their responses to applied magnetic and electric fields. In several cases, fermions in the interior of the material show their presence on the surface via the appearance of electron states called Fermi arcs, which link the different types of fermion states in the material’s bulk.

The research, published online this week in the journal Science, was conducted by a team at Princeton University in collaboration with researchers at the Donostia International Physics Center (DIPC) in Spain and the Max Planck Institute for Chemical Physics of Solids in Germany. The investigators propose that many of the materials hosting the new types of fermions are “protected metals,” which are metals that do not allow, in most circumstances, an insulating state to develop. This research represents the newest avenue in the physics of “topological materials,” an area of science that has already fundamentally changed the way researchers see and interpret states of matter.

The team at Princeton included Barry Bradlyn and Jennifer Cano, both associate research scholars at the Princeton Center for Theoretical Science; Zhijun Wang, a postdoctoral research associate in the Department of Physics, Robert Cava, the Russell Wellman Moore Professor of Chemistry; and B. Andrei Bernevig, associate professor of physics. The research team also included Maia Vergniory, a postdoctoral research fellow at DIPC, and Claudia Felser, a professor of physics and chemistry and director of the Max Planck Institute for Chemical Physics of Solids.

For the past century, gapless fermions, which are quantum particles with no energy gap between their highest filled and lowest unfilled states, were thought to come in three varieties: Dirac, Majorana and Weyl. Condensed matter physics, which pioneers the study of quantum phases of matter, has become fertile ground for the discovery of these fermions in different materials through experiments conducted in crystals. These experiments enable researchers to explore exotic particles using relatively inexpensive laboratory equipment rather than large particle accelerators.

In the past four years, all three varieties of gapless fermions have been theoretically predicted and experimentally observed in different types of crystalline materials grown in laboratories around the world. The Weyl fermion was thought to be last of the group of predicted quasiparticles in nature. Research published earlier this year in the journal Nature (Wang et al., doi:10.1038/nature17410) has shown, however, that this is not the case, with the discovery of a bulk insulator which hosts an exotic surface fermion.

In the current paper, the team predicted and classified the possible exotic fermions that can appear in the bulk of materials. The energy of these fermions can be characterized as a function of their momentum into so-called energy bands, or branches. Unlike the Weyl and Dirac fermions, which, roughly speaking, exhibit an energy spectrum with 2- and 4-fold branches of allowed energy states, the new fermions can exhibit 3-, 6- and 8-fold branches. The 3-, 6-, or 8-fold branches meet up at points – called degeneracy points – in the Brillouin zone, which is the parameter space where the fermion momentum takes its values.

“Symmetries are essential to keep the fermions well-defined, as well as to uncover their physical properties,” Bradlyn said. “Locally, by inspecting the physics close to the degeneracy points, one can think of them as new particles, but this is only part of the story,” he said.

Cano added, “The new fermions know about the global topology of the material. Crucially, they connect to other points in the Brillouin zone in nontrivial ways.”

During the search for materials exhibiting the new fermions, the team uncovered a fundamentally new and systematic way of finding metals in nature. Until now, searching for metals involved performing detailed calculations of the electronic states of matter.

“The presence of the new fermions allows for a much easier way to determine whether a given system is a protected metal or not, in some cases without the need to do a detailed calculation,” Wang said.

Verginory added, “One can just count the number of electrons of a crystal, and figure out, based on symmetry, if a new fermion exists within observable range.”

The researchers suggest that this is because the new fermions require multiple electronic states to meet in energy: The 8-branch fermion requires the presence of 8 electronic states. As such, a system with only 4 electrons can only occupy half of those states and cannot be insulating, thereby creating a protected metal.

“The interplay between symmetry, topology and material science hinted by the presence of the new fermions is likely to play a more fundamental role in our future understanding of topological materials – both semimetals and insulators,” Cava said.

Felser added, “We all envision a future for quantum physical chemistry where one can write down the formula of a material, look at both the symmetries of the crystal lattice and at the valence orbitals of each element, and, without a calculation, be able to tell whether the material is a topological insulator or a protected metal.”

Read the abstract.

Funding for this study was provided by the US Army Research Office Multidisciplinary University Research Initiative, the US Office of Naval Research, the National Science Foundation, the David and Lucile Packard Foundation, the W. M. Keck Foundation, and the Spanish Ministry of Economy and Competitiveness.

Study Models How the Immune System Might Evolve to Conquer HIV (PLOS Genetics)

Posted on by Catherine Zandonella

By Katherine Unger Baillie, courtesy of the University of Pennsylvania

It has remained frustratingly difficult to develop a vaccine for HIV/AIDS, in part because the virus, once in our bodies, rapidly reproduces and evolves to escape being killed by the immune system.

“The viruses are constantly producing mutants that evade detection,” said Joshua Plotkin, a professor in the University of Pennsylvania’s Department of Biology in the School of Arts & Sciences. “A single person with HIV may have millions of strains of the virus circulating in the body.”

Yet the body’s immune system can also evolve. Antibody-secreting B-cells compete among themselves to survive and proliferate depending on how well they bind to foreign invaders. They dynamically produce diverse types of antibodies during the course of an infection.

In a new paper in PLOS Genetics, Plotkin, along with postdoctoral researcher Jakub Otwinowski and Armita Nourmohammad, an associate research scholar at Princeton University’s Lewis-Sigler Institute for Integrative Genomics, mathematically modeled these dueling evolutionary processes to understand the conditions that influence how antibodies and viruses interact and adapt to one another over the course of a chronic infection.

Notably, the researchers considered the conditions under which the immune system gives rise to broadly neutralizing antibodies, which can defeat broad swaths of viral strains by targeting the most vital and immutable parts of the viral genome. Their findings, which suggest that presenting the immune system with a large diversity of viral antigens may be the best way to encourage the emergence of such potent antibodies, have implications for designing vaccines against HIV and other chronic infections.

“This isn’t a prescription for how to design an HIV vaccine,” Plotkin said, “but our work provides some quantitative guidance for how to prompt the immune system to elicit broadly neutralizing antibodies.”

The biggest challenge in attempting to model the co-evolution of antibodies and viruses is keeping track of the vast quantity of different genomic sequences that arise in each population during the course of an infection. So the researchers focused on the statistics of the binding interactions between the virus and antibodies.

“This is the key analytical trick to simplify the problem,” said Otwinowski. “It would otherwise be impossible to track and write equations for all the interactions.”

The researchers constructed a model to examine how mutations would affect the binding affinity between antibodies and viruses. Their model calculated the average binding affinities between the entire population of viral strains and the repertoire of antibodies over time to understand how they co-evolve.

“It’s one of the things that is unique about our work,” said Nourmohammad. “We’re not only looking at one virus binding to one antibody but the whole diversity of interactions that occur over the course of a chronic infection.”

What they saw was an S-shaped curve, in which sometimes the immune system appeared to control the infection with high levels of binding, but subsequently a viral mutation would arise that could evade neutralization, and then binding affinities would go down.

“The immune system does well if there is active binding between antibodies and virus,” Plotkin said, “and the virus does well if there is not strong binding.”

Such a signature is indicative of a system that is out of equilibrium where the viruses are responding to the antibodies and vice versa. The researchers note that this signature is likely common to many antagonistically co-evolving populations.

To see how well their model matched with data from an actual infection, the researchers looked at time-shifted experimental data from two HIV patients, in which their antibodies were collected at different time points and then “competed” against the viruses that had been in their bodies at different times during their infections.

They saw that these patient data are consistent with their model: Viruses from earlier time points would be largely neutralized by antibodies collected at later time points but could outcompete antibodies collected earlier in infection.

Finally, the researchers used the model to try to understand the conditions under which broadly neutralizing antibodies, which could defeat most strains of virus, would emerge and rise to prominence.

“Despite the effectiveness of broadly neutralizing antibodies, none of the patients with these antibodies has been cured of HIV,” Plotkin said. “It’s just that by the time they develop them, it’s too late and their T-cell repertoire is depleted. This raises the intriguing idea that, if only they could develop these antibodies earlier in infection, they might be prepared to combat an evolving target.”

“The model that we built,” Nourmohammad said, “was able to show that, if viral diversity is very large, the chance that these broadly neutralizing antibodies outcompete more specifically targeted antibodies and proliferate goes up.”

The finding suggests that, in order for a vaccine to elicit these antibodies, it should present a diverse set of viral antigens to the host. That way no one specialist antibody would have a significant fitness advantage, leaving room for the generalist, broadly neutralizing antibodies to succeed.

The researchers said that there has been little theoretical modeling of co-evolutionary systems such as this one. As such, their work could have implications for other co-evolution scenarios.

“Our theory can also apply to other systems, such as bacteria-phage co-evolution,” said Otwinowski, in which viruses infect bacteria, a process that drives bacterial evolution and ecology.

“It could also shed light on the co-evolution of the influenza virus in the context of evolving global immune systems,” Nourmohammad said.

Read the article.

The work was supported by funding from the U.S. National Science Foundation, James S. McDonnell Foundation, David and Lucile Packard Foundation, U.S. Army Research Office and National Institutes of Health.

 

Role for enhancers in bursts of gene activity (Cell)

Posted on by Catherine Zandonella

 

By Marisa Sanders for the Office of the Dean for Research

A new study by researchers at Princeton University suggests that sporadic bursts of gene activity may be important features of genetic regulation rather than just occasional mishaps. The researchers found that snippets of DNA called enhancers can boost the frequency of bursts, suggesting that these bursts play a role in gene control.

The researchers analyzed videos of Drosophila fly embryos undergoing DNA transcription, the first step in the activation of genes to make proteins. In a study published on July 14 in the journal Cell, the researchers found that placing enhancers in different positions relative to their target genes resulted in dramatic changes in the frequency of the bursts.

“The importance of transcriptional bursts is controversial,” said Michael Levine, Princeton’s Anthony B. Evnin ’62 Professor in Genomics and director of the Lewis-Sigler Institute for Integrative Genomics. “While our study doesn’t prove that all genes undergo transcriptional bursting, we did find that every gene we looked at showed bursting, and these are the critical genes that define what the embryo is going to become. If we see bursting here, the odds are we are going to see it elsewhere.”

The transcription of DNA occurs when an enzyme known as RNA polymerase converts the DNA code into a corresponding RNA code, which is later translated into a protein. Researchers were puzzled to find about ten years ago that transcription can be sporadic and variable rather than smooth and continuous.

In the current study, Takashi Fukaya, a postdoctoral research fellow, and Bomyi Lim, a postdoctoral research associate, both working with Levine, explored the role of enhancers on transcriptional bursting. Enhancers are recognized by DNA-binding proteins to augment or diminish transcription rates, but the exact mechanisms are poorly understood.

Until recently, visualizing transcription in living embryos was impossible due to limits in the sensitivity and resolution of light microscopes. A new method developed three years ago has now made that possible. The technique, developed by two separate research groups, one at Princeton led by Thomas Gregor, associate professor of physics and the Lewis-Sigler Institute for Integrative Genomics, and the other led by Nathalie Dostatni at the Curie Institute in Paris, involves placing fluorescent tags on RNA molecules to make them visible under the microscope.

The researchers used this live-imaging technique to study fly embryos at a key stage in their development, approximately two hours after the onset of embryonic life where the genes undergo fast and furious transcription for about one hour. During this period, the researchers observed a significant ramping up of bursting, in which the RNA polymerase enzymes cranked out a newly transcribed segment of RNA every 10 or 15 seconds over a period of perhaps 4 or 5 minutes per burst. The genes then relaxed for a few minutes, followed by another episode of bursting.

The team then looked at whether the location of the enhancer – either upstream from the gene or downstream – influenced the amount of bursting. In two different experiments, Fukaya placed the enhancer either upstream of the gene’s promoter, or downstream of the gene and saw that the different enhancer positions resulted in distinct responses. When the researchers positioned the enhancer downstream of the gene, they observed periodic bursts of transcription. However when they positioned the enhancer upstream of the gene, the researchers saw some fluctuations but no discrete bursts. They found that the closer the enhancer is to the promoter, the more frequent the bursting.

To confirm their observations, Lim applied further data analysis methods to tally the amount of bursting that they saw in the videos. The team found that the frequency of the bursts was related to the strength of the enhancer in upregulating gene expression. Strong enhancers produced more bursts than weak enhancers. The team also showed that inserting a segment of DNA called an insulator reduced the number of bursts and dampened gene expression.

In a second series of experiments, Fukaya showed that a single enhancer can activate simultaneously two genes that are located some distance apart on the genome and have separate promoters. It was originally thought that such an enhancer would facilitate bursting at one promoter at a time—that is, it would arrive at a promoter, linger, produce a burst, and come off. Then, it would randomly select one of the two genes for another round of bursting. However, what was instead observed was bursting occurring simultaneously at both genes.

“We were surprised by this result,” Levine said. “Back to the drawing board! This means that traditional models for enhancer-promoter looping interactions are just not quite correct,” Levine said. “It may be that the promoters can move to the enhancer due to the formation of chromosomal loops. That is the next area to explore in the future.”

The study was funded by grants from the National Institutes of Health (U01EB021239 and GM46638).

Access the paper here:

Takashi Fukaya, Bomyi Lim & Michael Levine. Enhancer Control of Transcriptional Bursting, Cell (2016), Published July 14. EPub ahead of print June 9. http://dx.doi.org/10.1016/j.cell.2016.05.025