Anyone who has used a microscope in a biology class to study a plant cell will probably be able to recall a similar situation. It is easy to tell that a certain chloroplast is located above and to the right of the nucleus. But are both of them located on the same plane? Once you adjust the focus on the microscope, however, you see that the image of the nucleus becomes sharper while the image of the chloroplast blurs. One of them must be a little higher and one a little lower than the other. However, this method cannot give us precise details about their vertical positions.

The principle is very similar if you want to observe individual atoms instead of cells. So-called quantum gas microscopy can be used for this purpose. It allows you to straightforwardly determine the x and y coordinates of an atom. However, it is much more difficult to measure its z coordinate, i.e., the distance to the objective lens: In order to find out on what plane the atom is located, multiple images must be taken in which the focus is shifted across various different planes. This is a complex and time-consuming process.

Turning round specks into dumbbells

“We have now developed a method in which this process can be completed in one step,” explains Tangi Legrand from the Institute of Applied Physics (IAP) at the University of Bonn. “To achieve this, we use an effect that has already been known in theory since the 1990s but which had not yet been used in a quantum gas microscope.”

To experiment on the atoms, it is first necessary to cool them down significantly so that they are barely moving. Afterwards, it is possible, for example, to trap them in a standing wave of laser light. They then slip into the troughs of the wave similar to how eggs sit in an egg box. Once trapped, to reveal their position, they are exposed to an additional laser beam, which stimulates them to emit light. The resulting fluorescence shows up in the quantum gas microscope as a slightly blurred, round speck.

“We have now developed a special method to deform the wavefront of the light being emitted by the atom,” explains Dr. Andrea Alberti. The researcher, who has now moved from the IAP to the Max Planck Institute of Quantum Optics in Garching, also participated in the study. “Instead of the typical round specks, the deformed wavefront produces a dumbbell shape on the camera that rotates around itself. The direction in which this dumbbell points is dependent on the distance that the light had to travel from the atom to the camera.”

“The dumbbell thus acts a bit like the needle on a compass, allowing us to read off the z coordinate according to its orientation,” says Prof. Dr. Dieter Meschede. The IAP researcher, whose research group carried out the study, is also a member of the transdisciplinary research area “Matter” at the University of Bonn.

Important for quantum mechanics experiments

The new method makes it possible to precisely determine the position of an atom in three dimensions with one single image. This is important, for example, if you want to carry out quantum mechanics experiments with atoms because it is often essential to be able to precisely control or track their position. This allows researchers to make the atoms interact with one another in the desired way.

Furthermore, the method could also be used to help develop new quantum materials with special characteristics. “For example, we could investigate which quantum mechanical effects occur when atoms are arranged in a certain order,” explains Dr. Carrie Weidner from the University of Bristol. “This would allow us to simulate the properties of three-dimensional materials to some extent without having to synthesize them.”

The study, led by Professor Jun Suzuki of the Institute for Integrated Cell-Material Sciences (iCeMS), addresses a critical gap by directly targeting genes within testicular cells inside living organisms. Utilizing a genetic tool called CRISPR, which can be likened to genetic scissors, the researchers developed a method to investigate which genes contribute to healthy sperm production in living animals. Until now, this had mainly been done in cells cultivated in the laboratory. The researchers randomly disrupted genes by developing a method to introduce a collection of genetic tools in lentivirus into testicular cells in testes at high efficiency. Through this method, the researchers made it possible to analyze the effects of targeted genes on specific biochemical reactions in the sperm cells, such as the movement of lipids (fats) in cell membranes.

Using the method, the team focused on sperms with defective capacitation, a process through which sperms become capable of fertilizing an egg. They identified these sperms by measuring how much calcium they absorbed. By using this method in live animals, they were able to identify a specific gene, Rd3, as being crucial for maintaining sperm cell health, particularly during sperm cell development. Despite Rd3’s previous association with eye function, the team found it is also highly active in round sperm cells, an early stage in sperm production, and that it plays a significant role in regulating sperm health. This discovery was made possible by examining how Rd3 interacts with mitochondria, structures responsible for energy production within cells.

To further understand Rd3’s function, Suzuki and his colleagues developed Hub-Explorer, a computational tool that revealed Rd3’s impact on regulation of oxidative stress — a condition linked to cellular damage. Rd3’s role in regulating oxidative stress revealed its significance in maintaining sperm integrity during development.

“While women have many available birth control options, choices for men remain limited,” says Noguchi, a first author of this paper. “This new screening method holds promise by aiding the discovery of key molecules, potentially leading to new birth control options and infertility therapies for men.”

“These discoveries not only advance our understanding of sperm cell development but also demonstrate the potential to uncover mysteries in different biological processes,” adds Suzuki. “The method can also be applied to other tissues, potentially expediting the development of drugs for a wide range of diseases.”

Despite these advancements, challenges remain. The researchers observed a gradual decline in the number of cells with targeted genes, suggesting room for improvement. They are currently exploring alternative approaches to enhance the effectiveness of their technique, and they plan to apply it to investigate various biological processes and diseases in other areas of the body.

Findings of the study led by Gaurav Sahay and Yulia Eygeris of the Oregon State University College of Pharmacy and Renee Ryals of Oregon Health & Science University were published today in the Proceedings of the National Academy of Sciences.

Unlike other types of lipid nanoparticles that tend to accumulate in the liver, the ones in this study, based on the compound thiophene, are able to navigate their way to the tissues of the lungs and retina, where they deliver their therapeutic payload. The researchers refer to these new lipids as Thio-lipids.

The collaboration demonstrated, by using animal models, the possibility of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness and pulmonary disease.

“These nanoparticles filled with fatty lipids can encapsulate genetic medicines like mRNA and CRISPR-Cas9 gene editors, which can be used to treat and even cure rare genetic diseases,” said Eygeris, a senior research associate at OSU. “Chemical structures of the lipids determine how potent are the lipid nanoparticles and which organ they can reach from the bloodstream.”

Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein.

With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus’ spike protein, which triggers an immune response from the body.

As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina — which don’t work right because of a genetic mutation — to manufacture the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a group of disorders of varying severity and prevalence that affect one out of every few thousand people worldwide.

An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that results in persistent lung infection and affects 30,000 people in the U.S., with about 1,000 new cases identified every year.

One faulty gene — the cystic fibrosis transmembrane conductance regulator, or CFTR — causes the disease, which is characterized by lung dehydration and mucus buildup that blocks the airway.

The thiophene-based lipid nanoparticle study, which involved mice and non-human primates, stems from a $3.2 million grant to Sahay and Ryals from the National Eye Institute. The grant’s purpose is addressing limitations associated with the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV.

“AAV has limited packaging capacity compared to lipid nanoparticles and it can prompt an immune system response,” said Sahay, a professor of pharmaceutical sciences. “It also doesn’t do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited.”

Sahay calls the Thio-lipid findings “highly encouraging” but says more studies are needed, including research on the lipids’ long-term impact on retinal health.

“But we think our results serve as a proof of concept and we will continue to explore Thio-lipids in potential treatments of pulmonary and retinal genetic diseases,” he said.

In addition to the National Eye Institute, funding and research support were provided by the Oregon National Primate Research Center and the Casey Eye Institute.

CSHL Professor and HHMI Investigator Zachary Lippman and his team discovered that tomato and Arabidopsis thaliana plants can use very different regulatory systems to control the same exact gene. Incredibly, they linked this behavior to extreme genetic makeovers that occurred over 125 million years of evolution.

The scientists used genome editing to create over 70 mutant strains of tomato and Arabidopsis thaliana plants. Each mutation deleted a piece of regulatory DNA around a gene known as CLV3. They then analyzed the effect each mutation had on plant growth and development. When the DNA keeping CLV3 in check was mutated too much, fruit growth exploded.

Danielle Ciren, a recent CSHL School of Biological Sciences graduate who led this study, explains, “CLV3 helps plants develop normally. If it wasn’t turned on at the exact time that it is, then plants would look very different. All the fruits would be ginormous and not ideal. You have to balance growth and yield. If a plant has giant tomatoes but only two, is that as beneficial as a lower yield? There’s no simple solution. You’re always sacrificing something when you’re trying to get something improved.”

For tomatoes, engineering mutations near the beginning but not the end of the CLV3 gene dramatically affected fruit size. For Arabidopsis, areas around both parts of the gene needed to be disrupted. This indicates something happened over the last 125 million years that made the plants evolve differently. Exactly what occurred remains a mystery.

“You can’t go back to the common ancestor because they don’t exist anymore. So it’s hard to say what was the original state and how have things been mixed up,” says Ciren. “The most simple explanation is that there’s a regulatory element that’s conserved in some capacity, and it’s been altered in subtle ways. It is a bit unexpected.”

What is certain is that genetic regulation is not uniform between plant species. Unearthing these genetic differences could help make crop genome engineering more predictable. And that would be a big win not just for science but for farmers and plant breeders across the globe.

Initially detected with NASA’s Hubble Space Telescope, this galaxy — one of the youngest and most distant ever observed — is so bright that it is challenging scientists to understand why. Now, GN-z11 is giving up some of its secrets.

Vigorous Black Hole Is Most Distant Ever Found

A team studying GN-z11 with Webb found the first clear evidence that the galaxy is hosting a central, supermassive black hole that is rapidly accreting matter. Their finding makes this the farthest active supermassive black hole spotted to date.

“We found extremely dense gas that is common in the vicinity of supermassive black holes accreting gas,” explained principal investigator Roberto Maiolino of the Cavendish Laboratory and the Kavli Institute of Cosmology at the University of Cambridge in the United Kingdom. “These were the first clear signatures that GN-z11 is hosting a black hole that is gobbling matter.”

Using Webb, the team also found indications of ionized chemical elements typically observed near accreting supermassive black holes. Additionally, they discovered a very powerful wind being expelled by the galaxy. Such high-velocity winds are typically driven by processes associated with vigorously accreting supermassive black holes.

“Webb’s NIRCam (Near-Infrared Camera) has revealed an extended component, tracing the host galaxy, and a central, compact source whose colors are consistent with those of an accretion disk surrounding a black hole,” said investigator Hannah Übler, also of the Cavendish Laboratory and the Kavli Institute.

Together, this evidence shows that GN-z11 hosts a 2-million-solar-mass, supermassive black hole in a very active phase of consuming matter, which is why it’s so luminous.

Pristine Gas Clump in GN-z11’s Halo Intrigues Researchers

A second team, also led by Maiolino, used Webb’s NIRSpec (Near-Infrared Spectrograph) to find a gaseous clump of helium in the halo surrounding GN-z11.

“The fact that we don’t see anything else beyond helium suggests that this clump must be fairly pristine,” said Maiolino. “This is something that was expected by theory and simulations in the vicinity of particularly massive galaxies from these epochs — that there should be pockets of pristine gas surviving in the halo, and these may collapse and form Population III star clusters.”

Finding the never-before-seen Population III stars — the first generation of stars formed almost entirely from hydrogen and helium — is one of the most important goals of modern astrophysics. These stars are anticipated to be very massive, very luminous, and very hot. Their expected signature is the presence of ionized helium and the absence of chemical elements heavier than helium.

The formation of the first stars and galaxies marks a fundamental shift in cosmic history, during which the universe evolved from a dark and relatively simple state into the highly structured and complex environment we see today.

In future Webb observations, Maiolino, Übler, and their team will explore GN-z11 in greater depth, and they hope to strengthen the case for the Population III stars that may be forming in its halo.

The research on the pristine gas clump in GN-z11’s halo has been accepted for publication by Astronomy & Astrophysics. The results of the study of GN-z11’s black hole were published in the journal Nature on January 17, 2024. The data was obtained as part of the JWST Advanced Deep Extragalactic Survey (JADES), a joint project between the NIRCam and NIRSpec teams.

Until now, assistive dressing robots, designed to help an elderly person or a person with a disability get dressed, have been created in the laboratory as a one-armed machine, but research has shown that this can be uncomfortable for the person in care or impractical.

To tackle this problem, Dr Jihong Zhu, a robotics researcher at the University of York’s Institute for Safe Autonomy, proposed a two-armed assistive dressing scheme, which has not been attempted in previous research, but inspired by caregivers who have demonstrated that specific actions are required to reduce discomfort and distress to the individual in their care.

It is thought that this technology could be significant in the social care system to allow care-workers to spend less time on practical tasks and more time on the health and mental well-being of individuals.

Dr Zhu gathered important information on how care-workers moved during a dressing exercise, through allowing a robot to observe and learn from human movements and then, through AI, generate a model that mimics how human helpers do their task.

This allowed the researchers to gather enough data to illustrate that two hands were needed for dressing and not one, as well as information on the angles that the arms make, and the need for a human to intervene and stop or alter certain movements.

Dr Zhu, from the University of York’s Institute for Safe Autonomy and the School of Physics, Engineering and Technology, said: “We know that practical tasks, such as getting dressed, can be done by a robot, freeing up a care-worker to concentrate more on providing companionship and observing the general well-being of the individual in their care. It has been tested in the laboratory, but for this to work outside of the lab we really needed to understand how care-workers did this task in real-time.

“We adopted a method called learning from demonstration, which means that you don’t need an expert to programme a robot, a human just needs to demonstrate the motion that is required of the robot and the robot learns that action. It was clear that for care workers two arms were needed to properly attend to the needs of individuals with different abilities.

“One hand holds the individual’s hand to guide them comfortably through the arm of a shirt, for example, whilst at the same time the other hand moves the garment up and around or over. With the current one-armed machine scheme a patient is required to do too much work in order for a robot to assist them, moving their arm up in the air or bending it in ways that they might not be able to do.”

The team were also able to build algorithms that made the robotic arm flexible enough in its movements for it to perform the pulling and lifting actions, but also be prevented from making an action by the gentle touch of a human hand, or guided out of an action by a human hand moving the hand left or right, up or down, without the robot resisting.

Dr Zhu said: “Human modelling can really help with efficient and safe human and robot interactions, but it is not only important to ensure it performs the task, but that it can be halted or changed mid-action should an individual desire it. Trust is a significant part of this process, and the next step in this research is testing the robot’s safety limitations and whether it will be accepted by those who need it most.”

The research, in collaboration with researchers from TU Delft and Honda Research Institute Europe, was funded by the Honda Research Institute Europe.