Using scaffolds made of folded DNA, MIT engineers have come up with a new way to precisely assemble arrays of quantum rods. By depositing quantum rods onto a DNA scaffold in a highly controlled way, the researchers can regulate their orientation, which is a key factor in determining the polarization of light emitted by the array. This makes it easier to add depth and dimensionality to a virtual scene.

“One of the challenges with quantum rods is: How do you align them all at the nanoscale so they’re all pointing in the same direction?” says Mark Bathe, an MIT professor of biological engineering and the senior author of the new study. “When they’re all pointing in the same direction on a 2D surface, then they all have the same properties of how they interact with light and control its polarization.”

MIT postdocs Chi Chen and Xin Luo are the lead authors of the paper, which appears today in Science Advances. Robert Macfarlane, an associate professor of materials science and engineering; Alexander Kaplan PhD ’23; and Moungi Bawendi, the Lester Wolfe Professor of Chemistry, are also authors of the study.

Nanoscale structures

Over the past 15 years, Bathe and others have led in the design and fabrication of nanoscale structures made of DNA, also known as DNA origami. DNA, a highly stable and programmable molecule, is an ideal building material for tiny structures that could be used for a variety of applications, including delivering drugs, acting as biosensors, or forming scaffolds for light-harvesting materials.

Bathe’s lab has developed computational methods that allow researchers to simply enter a target nanoscale shape they want to create, and the program will calculate the sequences of DNA that will self-assemble into the right shape. They also developed scalable fabrication methods that incorporate quantum dots into these DNA-based materials.

In a 2022 paper, Bathe and Chen showed that they could use DNA to scaffold quantum dots in precise positions using scalable biological fabrication. Building on that work, they teamed up with Macfarlane’s lab to tackle the challenge of arranging quantum rods into 2D arrays, which is more difficult because the rods need to be aligned in the same direction.

Existing approaches that create aligned arrays of quantum rods using mechanical rubbing with a fabric or an electric field to sweep the rods into one direction have had only limited success. This is because high-efficiency light-emission requires the rods to be kept at least 10 nanometers from each other, so that they won’t “quench,” or suppress, their neighbors’ light-emitting activity.

To achieve that, the researchers devised a way to attach quantum rods to diamond-shaped DNA origami structures, which can be built at the right size to maintain that distance. These DNA structures are then attached to a surface, where they fit together like puzzle pieces.

“The quantum rods sit on the origami in the same direction, so now you have patterned all these quantum rods through self-assembly on 2D surfaces, and you can do that over the micron scale needed for different applications like microLEDs,” Bathe says. “You can orient them in specific directions that are controllable and keep them well-separated because the origamis are packed and naturally fit together, as puzzle pieces would.”

Assembling the puzzle

As the first step in getting this approach to work, the researchers had to come up with a way to attach DNA strands to the quantum rods. To do that, Chen developed a process that involves emulsifying DNA into a mixture with the quantum rods, then rapidly dehydrating the mixture, which allows the DNA molecules to form a dense layer on the surface of the rods.

This process takes only a few minutes, much faster than any existing method for attaching DNA to nanoscale particles, which may be key to enabling commercial applications.

“The unique aspect of this method lies in its near-universal applicability to any water-loving ligand with affinity to the nanoparticle surface, allowing them to be instantly pushed onto the surface of the nanoscale particles. By harnessing this method, we achieved a significant reduction in manufacturing time from several days to just a few minutes,” Chen says.

These DNA strands then act like Velcro, helping the quantum rods stick to a DNA origami template, which forms a thin film that coats a silicate surface. This thin film of DNA is first formed via self-assembly by joining neighboring DNA templates together via overhanging strands of DNA along their edges.

The researchers now hope to create wafer-scale surfaces with etched patterns, which could allow them to scale their design to device-scale arrangements of quantum rods for numerous applications, beyond only microLEDs or augmented reality/virtual reality.

“The method that we describe in this paper is great because it provides good spatial and orientational control of how the quantum rods are positioned. The next steps are going to be making arrays that are more hierarchical, with programmed structure at many different length scales. The ability to control the sizes, shapes, and placement of these quantum rod arrays is a gateway to all sorts of different electronics applications,” Macfarlane says.

“DNA is particularly attractive as a manufacturing material because it can be biologically produced, which is both scalable and sustainable, in line with the emerging U.S. bioeconomy. Translating this work towards commercial devices by solving several remaining bottlenecks, including switching to environmentally safe quantum rods, is what we’re focused on next,” Bathe adds.

The research was funded by the Office of Naval Research, the National Science Foundation, the Army Research Office, the Department of Energy, and the National Institute of Environmental Health Sciences.

Their study, “Soil Elemental Changes During Human Decomposition,” published in June 2023 by PLOS One, could benefit investigators searching for human remains in remote or hard-to access-vegetated areas.

“This study was part of a larger project where we were investing environmental changes in the vicinity of a decomposing body,” said Jennifer DeBruyn, co-author and professor in the Department of Biosystems and Soil Science (BESS). “Our bodies are concentrated in nutrients and other elements compared to the surrounding environment. As they break down, these nutrients are released into the environment, resulting in changes to soil and vegetation nearby.”

A greater understanding of how and when soil and vegetation changes in the presence of decomposing human remains may offer clues to both locating bodies and estimating how long they have been there.

To test their ideas, this study asks: What elements are released from the human body during decomposition and how does it influence the local soil environment?

“We have previously looked at the major elements of the body, namely carbon and nitrogen,” said DeBruyn, “But we know there are lots more in our bodies.”

The next most abundant elements in the body are sulfur, phosphorus, sodium, and potassium. As the soft tissues in test bodies decomposed, the team observed an expected pulse of these elements in the soils as they were released into the environment.

“What we were surprised to see was that we also had higher concentrations of calcium and magnesium than what we would expect from the input of the body alone,” said Stacy Taylor, lead author on the study and a postdoctoral researcher in DeBruyn’s lab. “While we do have calcium (Ca) and magnesium (Mg) in our bodies, much of it is tied up in our bones, which would take years or decades break down. Soils have capacity to bind cations like Ca²⁺ and Mg²⁺, so our hypothesis is that the changing conditions resulted in the release of these elements from the soil itself.”

They were also surprised to see an increase in some trace metals a few months into the soil testing, after soft tissues were largely decomposed.

“Again, the concentrations in soil were higher than what we would expect based on just what would be coming from the body,” said Taylor. “Decomposition fluids result in a gradual acidification of the soil over time, so our hypothesis is that as the pH was dropping, these trace metals were slowly being solubilized from mineral complexes in the soil.”

The big-picture take-away from their study could lead to new approaches in finding missing persons or in determining how long remains have been in a location.

“This study was an important documentation of the types of elements released during human decomposition and how they changed over time,” said DeBruyn. “It contributes to our broader understanding of local environmental changes during human decomposition, which may ultimately help us understand the timing of decomposition in cases where human remains are found outdoors.”

DeBruyn and her students and postdocs have been conducting research at the Anthropological Research Facility for over a decade, investigating the microbiological and environmental changes during human decomposition.

Their team for the study included DeBruyn, Taylor, and Michael Essington from BESS; Scott Lenaghan and Neal Stewart from the Center for Agricultural Synthetic Biology within the UT Institute of Agriculture; Amy Mundorff and Dawnie Steadman of the Forensic Anthropology Center, and Adrian Gonzalez, manager of the Water Quality Core Facility (WQCF) in the Department of Civil and Environmental Engineering.

The WQCF analyzed hundreds of soil samples that originated from underneath deceased human donors — those whose decision to volunteer their remains offers ongoing contribution to the furthering of this investigative science.

Ammonoids are a group of extinct marine mollusk animals that are now an iconic fossil group often collected by amateurs. Over 350 million years of evolution, ammonoids developed increasingly elaborate shells with fractal-like geometry. For nearly 200 years, scientists have debated the reason why these animals show a trend of increasing complexity in their shell structures. Dr. Robert Lemanis and Dr. Igor Zlotnikov from the B CUBE — Center for Molecular Bioengineering at TU Dresden created mechanical simulations of theoretical and computed tomography-based models to unveil a potential explanation: the intricate architecture of these shells may have been nature’s ingenious defense strategy against a wide array of predators.

“Over the course of 350 million years of evolution, ammonoids repeatedly evolved shells with increasingly complex inner walls. The persistence and repetitiveness of this trend imply some driving force; the question that has long remained unanswered is: what driving force? Opposition to water pressure, muscle attachments, respiration, Cartesian devils. All of these have been proposed as explanations for this trend but evidence for them is scarce. So we decided to explore a neglected idea,” explains Dr. Robert Lemanis, researcher in Dr. Zlotnikov’s group at the B CUBE.

The team’s findings propose a fascinating correlation between the evolving complexity of the ammonoid shell and its resilience against external forces. As these ancient creatures roamed the oceans, their shells shielded them against predators and other environmental factors. The intricate inner structures provided crucial reinforcement, making it progressively harder for predators to crack them.

“Consider that the ammonoid shell was a relatively thin structure and once it was fractured, the animal could not repair it. A robust shell — one that can resist the damage — provided higher chances of survival,” explains Dr. Lemanis.

In essence, the shell’s evolution could be a story of survival against the odds. Through countless years of adaptation and innovation, these ancient creatures crafted their defenses with remarkable precision. This new insight from the B CUBE researchers offers us a glimpse into the distant past, where the beauty of nature intertwines with the relentless pressures of survival.

“Our work bridges biology and engineering, underscoring how animals harness the power of fractal morphology to design more robust biomaterials. It can provide inspiration for resilient structural designs,” summarizes Dr. Zlotnikov, research group leader at the B CUBE.

Mitochondria are found in every cell in our bodies. The genes responsible for generating mitochondria are dispersed across both the nuclear DNA located in the nucleus of our cells and the mitochondrial DNA (mtDNA) located within each mitochondrion. Prior studies have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells, potentially leading to mitochondrial dysfunction.

To understand how SARS-CoV-2 impacts mitochondria, researchers from the Center for Mitochondrial and Epigenomic Medicine (CMEM) at CHOP along with their COV-IRT colleagues wanted to analyze mitochondrial gene expression to detect differences caused by the virus. To do this, they analyzed a combination of nasopharyngeal and autopsy tissues from affected patients and animal models.

“The tissue samples from human patients allowed us to look at how mitochondrial gene expression was affected at the onset and end of disease progression, while animal models allowed us to fill in the blanks and look at the progression of gene expression differences over time,” said the study’s first author Joseph Guarnieri, PhD, a postdoctoral research fellow with the CMEM at CHOP.

The study found that in autopsy tissue, mitochondrial gene expression had recovered in the lungs, but mitochondrial function remained suppressed in the heart as well as the kidneys and liver. When studying animal models and measuring the time when the viral load was at its peak in the lungs, mitochondrial gene expression was suppressed in the cerebellum even though no SARS-CoV-2 was observed in the brain. Additional animal models revealed that during the mid-phase of SARS-CoV-2 infection, mitochondrial function in the lungs was beginning to recover.

Taken together, these results reveal that host cells respond to initial infection in a way that involves the lungs, but over time, mitochondrial function in the lungs is restored, while in other organs, particularly the heart, mitochondrial function remains impaired.

“This study provides us with strong evidence that we need to stop looking at COVID-19 as strictly an upper respiratory disease and start viewing it as a systemic disorder that impacts multiple organs,” said co-senior author Douglas C. Wallace, PhD, director of the CMEM at CHOP. “The continued dysfunction we observed in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to the internal organs of these patients.”

While future studies using this data will study how systemic immune and inflammatory responses may be responsible for more severe disease in some patients, the research team did find a potential therapeutic target in microRNA 2392 (miR-2392), which was shown to regulate mitochondrial function in human tissue samples used in this study.

“This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see,” said co-senior author Afshin Beheshti, PhD, a biostatistician, a visiting researcher at The Broad Institute, and founder and President of COV-IRT. “Neutralizing this microRNA might be able to impede the replication of the virus, providing an additional therapeutic option for patients who are at risk for more serious complications related to the disease.”

Earlier this year, The Gates Foundation provided funding to Dr. Wallace and CMEM for research into how mtDNA variation among world populations might affect mitochondrial function and thus individual sensitivity to SARS-CoV-2. According to Wallace, the demonstration that SARS-CoV-2 markedly affects mitochondrial function supports the hypothesis that individual differences in mitochondrial function could be a factor in individual severity of COVID-19.

This work was also supported by the Division of Intramural Research, NIAID, NIH and, in part, by the Bill & Melinda Gates Foundation grant INV-046722.

Bacterial resistance to antibiotics is a growing problem associated with millions of deaths around the world every year. Understanding how bacteria evolve resistance is key to developing more effective antibiotics and strategies for using them.

In recent years, albicidin has emerged as a promising antibiotic capable of killing a wide range of bacterial species by disrupting their DNA replication. Researchers are working to develop new albicidin-based medications; yet, despite its promise, some bacteria are able to develop resistance to albicidin.

To further investigate albicidin resistance mechanisms, Saathoff and colleagues conducted a suite of experiments employing a broad set of tools, including RNA sequencing, protein analysis, X-ray crystallography, and molecular modeling. They found that two bacteria often associated with human infection — Salmonella typhimurium and Escherichia coli — develop resistance to albicidin when exposed to increasingly higher concentrations of the compound. Their analysis narrowed down the source of this resistance to an increase in the number of copies of a gene known as STM3175 (YgiV) in the bacterial cells, which is amplified in each new generation of cells as they multiply. STM3175 encodes a protein that interacts with albicidin in such a way that protects the bacteria from it.

Further experiments showed that the same albicidin-resistance mechanism is widespread among both pathogenic and harmless bacteria, including the microbes Vibrio vulnificus, which can infect wounds, and Pseudomonas aeruginosa, which can cause pneumonia and other infections. These findings could help inform the ongoing development of albicidin-based antibiotic strategies.

The authors add, “Our study reveals a gene duplication and amplification-based mechanism of a transcriptional regulator in Gram-negative bacteria, that mediates resistance to the peptide antibiotic albicidin.”

Modern-day people carry in their cells a small quantity of DNA deriving from other human species, namely the Neanderthals and the elusive Denisovans. Back in 2018, scientists announced to the world the discovery of an individual, later nicknamed Denny, who lived 90,000 years ago and who was identified as a daughter to a Denisovan father and a Neanderthal mother[Slon et al. 2018]. Denny, along with fellow mixed-ancestry individuals found at Denisova cave, testifies that interbreeding was probably common among hominins, and not limited to our own species Homo sapiens.

To unravel when and where human hybridization took place, scientists usually rely on paleo-genomic analysis of extremely rare fossil specimens and their even scarcer ancient DNA content. In the new Science paper, the team of climate experts and paleo-biologists from South Korea and Italy pursued a different approach. Using existing paleo-anthropological evidence, genetic data and supercomputer simulations of past climate, the team found that Neanderthals and Denisovans had different environmental preferences. More specifically, Denisovans were much more adapted to cold environments, characterized by boreal forests and even tundra, compared to their Neanderthal cousins who preferred temperate forests and grassland. “This means that their habitats of choice were separated geographically, with Neanderthals typically preferring southwestern Eurasia and Denisovans the northeast,” says Dr. Jiaoyang Ruan, postdoctoral researcher at the IBS Center for Climate Physics (ICCP), South Korea and lead author of the study.

However, according to their realistic computer simulations the scientists found that in warm interglacial periods, when Earth’s orbit around the Sun was more elliptic and northern hemisphere summer occurred closer to the Sun, the hominin habitats began to overlap geographically. “When Neanderthals and Denisovans shared a common habitat, there were more encounters and interactions among the groups, which would have increased the chance of interbreeding,” adds Prof. Axel Timmermann, corresponding author of the study and director of the ICCP and professor at Pusan National University.

The simulation of past habitat overlaps does not only put the first generation Neanderthal/Denisovan hybrid Denny into a climatic context, but it also agrees with other known episodes of interbreeding ~78, 120 thousand years ago. Future paleo-genetic reconstructions can be used to test the robustness of the new supercomputer model-based predictions of potential interbreeding intervals around 210 and 320 thousand years ago.

To further determine the climate drivers of the east-west interbreeding seesaw, the scientists looked more closely at how vegetation patterns changed over Eurasia during the past 400 thousand years. They discovered that elevated atmospheric CO₂ concentrations and mild interglacial conditions caused an eastward expansion of temperate forest into central Eurasia which created dispersal corridors for Neanderthals into Denisovan lands. “It is as if glacial-interglacial shifts in climate created the stage for a unique and long-lasting human love story, whose genetic traces are still visible today,” comments Dr. Ruan.

One of the key challenges the researchers faced in their study was to estimate the preferred climatic conditions for Denisovans. “To deal with the very sparse Denisovan dataset, we had to devise new statistical tools, which could also account for known ancestral relationships amongst human species,” says Prof. Pasquale Raia from University of Naples, Federico II in Italy, co-author of the study. “This allowed us for the first time to estimate where Denisovans could have lived. To our surprise, we found that, apart from areas in Russia and China, also northern Europe would have been a suitable environment for them,” he adds.

Whether Denisovans ever lived west of the Altai mountains is unknown; but it can be tested using large-sample genetic analyses of Denisovan ancestry in European populations. Such analysis is expected to shed new light on the relationship between early dispersal, habitat encroachment and human genetic diversification.