Research roundup

Insights & Outcomes: A spintronics triumph and new info from organoids

(Illustration by Eri Griffin)

This month, Insights & Outcomes calls attention to important, even elegant, discoveries that occur when Yale researchers investigate the basic science of tiny, intricate phenomena: the spinning of electrons in magnetic materials, three-dimensional replicas of the human brain, structures that protect RNA from decay — and more.

As always, you can find more science and medicine research news on YaleNews’ Science & Technology and Health & Medicine pages.

A spintronics success story

Yale researchers working with scientists at the U.S. Department of Energy’s Brookhaven National Laboratory have demonstrated the ability to control spin dynamics in magnetic materials by altering the materials’ thickness. The research stands as a major achievement in the emerging field of spintronics — the manipulation of electron spin — and could prove useful in developing the next generation of electronics.

Traditional electronics rely on electron charge to transmit information. But as electrical current flows through a device, it dissipates heat, a factor that limits just how small a device can be without overheating or performing poorly. An alternative design approach is to transmit information via electron spin — the rotation of electrons on an axis — which moves through a material like a current.

Studying thin films of iron — as thin as one nanometer — the researchers discovered that the material’s thickness could act as a “knob” for fine tuning and controlling spin dynamics.

The team credited the advanced capabilities of the Soft Inelastic X-ray Scattering (SIX) beamline at the National Synchrotron Light Source II (NSLS-II) at Brookhaven for making the finding possible. “This experiment was an inspiring opportunity to perform hands-on synchrotron measurements with world-class scientists at NSLS-II. Because Yale and the NSLS-II are only two hours away, I was able to fully participate in the experiment,” said Sangjae Lee, a graduate student in the lab of Charles Ahn, the chair and John C. Malone Professor of Applied Physics, Mechanical Engineering & Materials Science, and Physics, at Yale.

Lee, Ahn, and Frederick J. Walker are Yale co-authors of the new study in Nature Materials.

All about those organoids

Scientists studying early brain development have traditionally relied upon tracking interactions of stem cells laid out in a single layer across a lab dish. However, Yale School of Medicine researchers explain why nothing beats the three dimensions of an organoid replica in demonstrating how a brain is built.

Stem cells can be harvested from living individuals with, say, schizophrenia, which allows scientists to look for aberrations as these cells differentiate into more specialized cells that make up the brain. Researchers looking for the origins of neurodegenerative diseases usually monitor the progression of these progenitor cells interacting in single or monolayers in a laboratory dish. However, the ability to create organoids — small, three-dimensional replicas of developing brain — has provided new insights.

Yale researchers — led by co-corresponding authors Flora Vaccarino of the Child Study Center and Gianfilippo Coppola of the Department of Pathology — compared gene expression patterns and the architecture of cells in both research models. They found that in organoids, stem cells are able to form layers of undifferentiated progenitor cells which multiply and gain the ability to signal to each other in the 3D environment. When these precursor cells stop dividing, they migrate and form layers of neurons that mimic those of particular brain regions and take on specialized roles. By contrast, within the two-dimensional confines of laboratory dishes, progenitors and neurons fail to form these layered networks and have decreased ability to communicate with each other, which hinders brain development.

The researchers reported their findings in the journal Stem Cell Reports. Soraya Scuderi of the Child Study Center and Giovanna Altobelli of University of Naples Federico II are co-first authors.

Finding the triggers for psoriasis inflammation

The itchy dryness of psoriasis is caused by chronic inflammation, but what type of immune system cells are responsible for the irritating discomfort? One of the chief suspects is a particular type of innate lymphoid cell (ILC) called ILC3, which resides in the skin and secretes molecules that cause inflammation and exacerbate psoriasis. However, researchers at the Yale School of Medicine and the Broad Institute report that, under the right conditions, multiple ILC culprits are capable of triggering inflammation that causes psoriasis. In a series of experiments, researchers showed that a broad range of ILCs can produce the same immune molecules in response to inflammation as ILC3s.

Our data confirm that ILCs in the skin exist in continuously changing states and that stresses such as inflammation can activate different groups of ILCs to trigger pro-inflammatory genes and proteins that ILC3s use to induce pathology,” said co-lead author Piotr Bielecki, who in collaboration with scientists at the Broad Institute conducted the experiments in lab of Yale immunobiologist Richard Flavell.

Understanding the fluid nature of the immune response can help guide new treatments for psoriasis and possibly other chronic inflammatory diseases, the authors said. The work was published Feb. 3 in the journal Nature.

Synthetic chemistry with a STING

One of the big pushes in cancer research involves STING — “stimulator of interferon genes” — a protein in the human immune system that can tear into tumors when activated. Now a team led by Scott Miller, the Irénée du Pont Professor of Chemistry, has discovered several types of catalysts that orchestrate key bonding in critical reactions that assemble nucleotide linkages. These linkages are important for synthesizing naturally occurring nucleic acids, which are central to an assortment of therapies — including many cancer therapies. “We demonstrated this with the synthesis of a type of compound that has been receiving lots of attention for modulation of the so-called ‘STING’ pathway,” Miller said.

Miller’s team, including co-first authors Aaron Featherston, Yongseok Kwon, and Matthew Pompeo, worked with scientists from Takeda Pharmaceuticals International Co. on the research. The study appears in the journal Science.

Protecting the poly(A) tail

Life’s most crucial instructions are carried out by RNAs, which can ferry information encoded in DNA to ribosomes to either produce proteins or act independently to regulate cellular activities. The addition of a polyadenylate (poly(A)) tail to the end of RNA molecules is common in almost all organisms. In conjunction with other RNA elements, this tail plays a central role in protecting RNA against decay. One way that the RNA in turn protects its poly(A) tail is by forming a structure composed of three strands, or triple helix, near its end.

Now a Yale research team — from the lab of Joan Steitz, the Sterling Professor of Molecular Biophysics and Biochemistry — has used x-ray crystallography to capture the high-resolution structure of an additional RNA structure that protects the poly(A) tail, illustrating the elegant way in which it works. “This novel RNA structure creates a molecular pocket that hides the very end of the poly(A) tail from cellular enzymes designed to degrade RNA from that end,” said Seyed Torabi, a postdoctoral researcher in the Steitz lab and lead author of the study.

This hiding strategy is a powerful mechanism to regulate RNA stability and activity, the Yale team showed. “Our structure might also reveal the ancestral role of poly(A) tails in protecting RNA from decay,” Torabi said. The research was published Feb. 5 in the journal Science.

Research redux

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