Cancer immunotherapy has revolutionised treatment for patients, whereby the body’s own immune system is harnessed to destroy cancer cells.

Typically, several molecules restrain the ability of T cells to target cancer cells and developing approaches to limit this restraining effect can lead to improved effectiveness of cancer immunotherapy.

Research published in Science Immunology has determined the structure of how an inhibitory molecule, LAG3, interacts with its main ligand and provides a new targeted approach to improving the effectiveness of immunotherapy for certain forms of cancer.

The publication is the first to show the crystal structure of a human LAG-3/HLA-II complex and provides a better foundation for development of blocking LAG-3 therapeutics.

Led by Professor Jamie Rossjohn at Monash University’s Biomedicine Discovery Institute (BDI), in Melbourne, Australia, in collaboration with Immutep, this research resolves how the human LAG-3 receptor binds to HLA II molecules.

First author Dr Jan Petersen said: “The way the PD-1 and CTLA-4 immune checkpoint molecules bind to their respective ligands has been resolved for many years.

“However, the resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, has remained elusive.

“Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural foundation to harness rationally for future development of antibodies and small molecule therapeutics designed to block LAG-3 activity.”

Dr Frédéric Triebel, Immutep’s CSO, added: “These findings add to the strong foundation of our work with Professor Rossjohn and his team to develop a deeper understanding of the structure and function of the LAG-3 immune control mechanism, particularly as it relates to our anti-LAG-3 small molecule program.”

The struggle of our cells

Imagine trying to fit two meters of rope into a space much smaller than the tip of a needle — that’s the challenge every cell in your body faces when packing its DNA into its tiny nucleus. To achieve this, nature employs ingenious strategies, like twisting the DNA into coils of coils, so-called ‘supercoils’ (see pictures for a visualisation) and wrapping it around special proteins for compact storage.

Small DNA loops regulate chromosome functions

However, compaction isn’t enough. Cells also need to regulate the chromosome structure to enable its function. For example, when genetic information needs to be accessed, the DNA is locally read off. In particular when it’s time for a cell to divide, the DNA must first unpack, duplicate, and then properly separate into two new cells. Specialised protein machines called SMC complexes (Structural Maintenance of Chromosomes) play a critical role in these processes. Just a few years ago, scientists at Delft and other places discovered that these SMC proteins are molecular motors that make long loops in our DNA, and that these loops are the key regulators of chromosome function.

A new twist

In the lab of Cees Dekker at TU Delft, postdocs Richard Janissen and Roman Bath now provide clues that help to crack this puzzle. They deloped a new way to use ‘magnetic tweezers’ by which they could watch individual SMC proteins make looping steps in DNA. Importantly, they were also able to resolve if the SMC protein would change the twist in the DNA. And strikingly, the team found that it did: the human SMC protein cohesin does indeed not only pull DNA into a loop, but also twists the DNA in a left-handed way by 0.6 turns in each step of creating the loop.

A glimpse into the evolution of SMC proteins

What’s more, the team found that this twisting action isn’t unique to humans. Similar SMC proteins in yeast behave the same way. Strikingly, all the various types of SMC proteins from human and yeast add the same amount of twist — they turn DNA 0.6 times at every at every DNA loop extrusion step. This shows that the DNA extrusion and twisting mechanisms stayed the same for very long times during evolution. No matter whether DNA is looped in humans, yeast, or any other cell — nature employs the same strategy.

Essential clues

These new findings will provide essential clues for resolving the molecular mechanism of this new type of motor. Additionally, they make clear that DNA looping also affects the supercoiling state of our chromosomes, which directly affects processes like gene expression. Finally, these SMC proteins are related to various diseases such as Cornelia de Lange Syndrome, and a better understanding of these processes is vital for tracking down the molecular origins of these serious illnesses.

The air around us contains a powerful solution for making agriculture more sustainable. Researchers at Stanford University and King Fahd University of Petroleum and Minerals in Saudi Arabia have developed a prototype device that can produce ammonia — a key fertilizer ingredient — using wind energy to draw air through a mesh. The approach they developed, if perfected, might eliminate the need for a century-old method that produces ammonia by combining nitrogen and hydrogen at high pressures and temperatures. The older method consumes 2% of global energy and contributes 1% of annual carbon dioxide emissions from its reliance on natural gas.

The study, published Dec. 13 in Science Advances, involved the first on-site — rather than in a lab — demonstration of the technology. The researchers envision someday integrating the device into irrigation systems, enabling farmers to generate fertilizer directly from the air.

“This breakthrough allows us to harness the nitrogen in our air and produce ammonia sustainably,” said study senior author Richard Zare, the Marguerite Blake Wilbur Professor in Natural Science in the Stanford School of Humanities and Sciences. “It’s a significant step toward a decentralized and eco-friendly approach to agriculture.”

A cleaner alternative

In preparation for designing their device, the researchers studied how different environmental factors — like humidity, wind speed, salt levels, and acidity — affect ammonia production. They also looked at how the size of water droplets, the concentration of the solution, and the contact of water with materials that do not dissolve in water impact the process. Lastly, they tested the best mix of iron oxide and an acid polymer with fluorine and sulfur to determine the ideal conditions for producing ammonia and understand how these catalyst materials interact with water droplets.

The Stanford team’s process makes ammonia cleanly and inexpensively and utilizes the surrounding air to get nitrogen and hydrogen from water vapor. By passing air through a mesh coated with catalysts to facilitate the necessary reaction, the researchers produced enough ammonia with a sufficiently high concentration to serve as a hydroponic fertilizer in greenhouse settings. Unlike traditional methods, the new technique operates at room temperature and standard atmospheric pressure, requiring no external voltage source to be attached to the mesh. Farmers could run the portable device onsite, eliminating the need to purchase and ship fertilizer from a manufacturer.

“This approach significantly reduces the carbon footprint of ammonia production,” said study lead author Xiaowei Song, a chemistry research scientist at Stanford.

In laboratory experiments, the team demonstrated further potential by recycling water through a spraying system, achieving ammonia concentrations sufficient to fertilize plants grown in a greenhouse after just two hours. By incorporating a filter made from a microporous stone material, this approach could produce enough ammonia to support broader agricultural applications.

A future without fossil fuels

The device is two to three years away from being market-ready, according to study co-author Chanbasha Basheer of King Fahd University of Petroleum and Minerals. In the meantime, the researchers plan to use increasingly large mesh systems to produce more ammonia. “There is a lot of room to develop this,” Basheer said.

Ammonia’s importance extends beyond fertilizers. As a clean energy carrier, it can store and transport renewable energy more efficiently than hydrogen gas due to its higher energy density. The innovation positions ammonia as a linchpin in decarbonizing industries like shipping and power generation.

“Green ammonia represents a new frontier in sustainability,” Zare said. “This method, if it can be scaled up economically, could drastically reduce our reliance on fossil fuels across multiple sectors.”

The study was funded by the U.S. Air Force Office of Scientific Research and King Fahd University of Petroleum and Minerals.

The team used sound wave, known as seismic, data to reveal Ice Age landforms buried beneath almost 1 km of mud in the North Sea. The results, reported in the journal Science Advances, suggest that the landforms were produced about 1 million years ago, when an ice sheet centred over Norway extended towards the British Isles.

This is important because the timing of this ice advance corresponds to a period of global cooling called the Mid-Pleistocene Transition.

Glacial landforms reveal how past ice sheets responded to changes in climate, which can help to make better predictions about how today’s ice sheets will respond to climate warming. A challenge is that glacial landforms are often buried beneath thick layers of sediment, preventing their identification.

Dr Christine Batchelor, Senior Lecturer in Physical Geography, Newcastle University, played a key role in the research by helping to map and interpret the landforms. “To fully understand the linkages between ice sheets and climate, we need to study how past ice sheets responded to long-term changes in climate,” said Dr Batchelor. “Using modern seismic data, our results suggests that ice sheets in northwest Europe expanded significantly in response to climate cooling about 1 million years ago.”

Dr Dag Ottesen from the Geological Survey of Norway, the paper’s lead author, said: “This study was made possible by the availability of 3D seismic data from the North Sea, which allowed us to examine the buried landforms in striking detail.”

3D seismic technology was developed to assess sediment suitability to host oil and gas or renewable infrastructures. However, this same data can be used to study buried landforms produced by glacial processes.

The mapped landscape includes streamlined features that were carved beneath the former ice sheet and ridges that record the imprint of the ice sheet as it started to retreat. Despite their ancient age, the landforms have striking resemblance to similar features produced by ice sheets much more recently.

The buried landforms provide new knowledge about the mechanisms by which ice sheets retreat. In order for such subdued landforms to remain unmodified, the former ice sheet must have retreated rapidly by lift-off and floatation of its frontal margin.

In addition to glacial landforms, the researchers also found elongated furrows incised into the former seabed, which they interpreted to have been produced by strong ocean currents. These landforms are even more deeply buried than the glacial landforms, showing that they were produced prior to the advance of the ice sheet.

“With our high-resolution data, we can see that the shape and size of the furrows is consistent with an origin as ocean current furrows,” said Dr Ottesen. “This differs from previous interpretations of these features as glacial landforms, re-writing our understanding of North Sea glacial history.”

By providing a new level of detail about the buried landforms, the findings shed light into the evolution of the North Sea in our recent geological past. The study shows that the North Sea was characterised by strong ocean currents prior to about 1 million years ago, after which it became more directly influenced by ice sheets.

The research team acknowledge that a limitation of the study is a lack of data about the precise age of the landforms.

“A wealth of seismic data are now available for the North Sea,” said Dr Batchelor. “The next step is to acquire long sediment cores that can allow researchers to better understand the timing of glacial events.”

Other co-authors are Helge Løseth at Equinor ASA, Trondheim and Harald Brunstad at Aker BP ASA, Trondheim.