A toxin from one of the world’s most venomous animals could one day help treat diabetes and endocrine disorders. The toxin in snails called consomatin is similar to somatostatin in humans, a peptide hormone that regulates blood sugar. In cone snail venom, consomatin’s specific and long-lasting effects help the animal hunt its prey, but it could also lead to the development of better drugs for sometimes fatal diseases–if we can understand how it works. The findings are detailed in a study published August 20 in the journal Nature Communications.

Fine-tuned venoms

Scientists have previously experimented with using cone snail venoms for creating less addictive opioid alternatives and new diabetes treatments. In 2016, scientists unlocked the structure of a fast-acting insulin that the snails use to stun their prey; a similar structure could be used to create an insulin that works faster in humans. In the new study, consomatin also exhibited enough precision to target single types of molecules. Researchers hope that drugs could be developed with the same amount of precision.

“Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it,” study co-author and University of Utah biochemist Helena Safavi said in a statement. “If you take one individual component out of the venom mixture and look at how it disrupts normal physiology, that pathway is often really relevant in disease.” 

[Related: What is a toxin?]

The team looked at the human hormone somatostatin that prevents the levels of blood sugar in the body from rising to dangerously high levels. The cone snail toxin consomatin also keeps blood sugar levels from increasing, but uses that as a way to stun and kill its prey. However, the team found that consomatin is more chemically stable and longer-lasting than the human hormone. This makes it a particularly promising blueprint for new drugs and treatment. 

In the study, the team looked at one of the most toxic marine cone snail–the geography cone. They are found along reefs in the Pacific and Indo-Pacific, where the snails stun and eat small fish. The team measured how the cone snail’s consomatin interacts with somatostatin’s targets in human cells in a dish. They found that consomatin mingles with one of the same proteins that somatostatin does. While human somatostatin directly interacts with several proteins, consomatin only works with one. This fine-tuned targeting means that the cone snail toxin can affect blood sugar levels and hormones, but not hit the other molecules around it.

According to the team, the cone snail toxin can hit its targets even more precisely than most specific synthetic drugs designed to regulate hormone levels. However, in its current form, the consomatin’s effects on blood sugar could make it dangerous to use to treat diabetes in humans. Studying its structure could help researchers design drugs for endocrine disorders that have fewer side effects in the future.

Earth’s chemists

Consomatin and somatostatin share an evolutionary history. Over millions of years, the cone snail turned its own hormone into a weapon. Importantly, consomatin doesn’t work alone. A 2022 study found that cone snail venom also includes another toxin which resembles insulin. This lowers blood sugar levels so quickly that the cone snail’s prey becomes unresponsive. Consomatin will then keep blood sugar levels from recovering, and the prey will ultimately die. 

[Related: This cone snail’s deadly venom could hold the key to better pain meds.]

“Cone snails are just really good chemists,” study co-author and University of Utah postdoctoral researcher Ho Yan Yeung said in a statement. “We think the cone snail developed this highly selective toxin to work together with the insulin-like toxin to bring down blood glucose to a really low level.”

Since several parts of the cone snail’s venom target blood sugar regulation, the venom may have other molecules with similar functions, including regulating glucose properties. A better understanding of the process at the molecular level could then be used to design better medications. 

The post Precise, lethal sea snail toxin could one day lead to better medicines appeared first on Popular Science.

Among the numerous snakes on planet Earth, pythons are well known for their incredible ability to swallow their prey whole. Some python species have been spotted taking down deer, cows, and even alligators, but they don’t generally eat every single day the way that most animals do. While scientists have observed their eating patterns for decades, less is known about how this affects their hearts. It turns out that to eat this way, pythons rapidly increase their heart rate, body mass, and energy output just for a meal. 

A study published August 19 in the journal Proceedings of the National Academy of Sciences (PNAS) found that python hearts appear to become less stiff, even while the blood pumping muscle is doing the work required to eat such a large meal. With more research, understanding how the python heart does this could be applied to heart diseases in humans one day. 

Feasting and fasting

In the wild, pythons must often go for months at a time without eating due to food scarcity. When they do eventually find food, they will really go for it and often eat a meal that can equal their body mass.

[Related: Scientists propose eating more python.]

“It [is] crucial to their survival to be able to have long fasting periods that are not harmful to them and to be able to consume these large meals intermittently,” study co-author and University of Colorado biologist Leslie Leinwand tells Popular Science. “One adaptive response to such a lifestyle is that almost all of the organs in their body get much larger in the first week after such meal consumption and after the meal is consumed, their organs shrink back to a little bigger than their fasting size.”

To learn more about the effects that their feeding style has on their bodies, Leinwand and the team compared the hearts of ball pythons (Python regius). One group of pythons had fasted for 28 days. The other group ate a meal of whole rats that were equivalent to a quarter of the snake’s body mass. 

Compared with the hearts of pythons who hadn’t eaten, the fed pythons increased their own mass by close to 25 percent after eating. The general structure of the heart was mostly unchanged after meals. 

In the fed pythons, the cardiac myofibrils–individual units in cardiac muscle cells that help the heart contract–had generated more force to eat. The cardiac myofibrils also relaxed more slowly and were less tense than myofibrils in the hearts of fasted pythons. The chromatin in the heart muscle cells that alters how genes respond to physiological stress in the fed pythons was also less condensed in the fed pythons compared to fasted pythons.

The cardiac ventricle tissues that help the heart pump blood were also less stiff in the fed pythons than the fasted ones. According to the study, it only took 24 hours after eating a large meal for the python heart to become much less stiff.

[Related: Stressed rattlesnakes just need a little help from their friends.]

Future applications for ‘stiff’ hearts

Stiffness in the heart can be troublesome in animal hearts because it can prevent blood from flowing properly. In humans, cardiac amyloidosis or “stiff heart syndrome” can lead to abnormal heartbeats and faulty heart signals. For pythons, their hearts appear to be avoiding the pitfalls of a stiff heart. Their hearts become much more stretchy while still producing the immense forces required to eat their prey. 

“We have shown that this organ size increase is what we call physiological–or healthy,” says Leinwend. “In the heart, such an increase is what is seen in highly conditioned athletes.”

However, there is still more research needed to determine how this can be used to help human hearts.

“If we could apply the biology of pythons that do this healthy thing in their hearts, it could be very helpful to people with heart disease,” says Leinwend. “There is a lot of fascinating biology in the world that can lead to better understanding and treatment of disease.”

The post How pythons can eat such giant meals appeared first on Popular Science.

The dodo is one of the most iconic—and misunderstood—extinct animals. Four hundred years after its extinction, the popular narrative remains that the flightless bird was simply too dumb, slow, and ungainly to withstand modern society’s arrival to its native island of Mauritius. But researchers are seeking justice for the unfairly maligned dodo and its extinct relative, the solitaire, by synthesizing centuries of scientific literature, historical accounts, and biological information into a single work providing clarification and revised taxonomic records.

In a study published in the August 2024 issue of Zoological Journal of the Linnean Society, a team collaborating between the University of Southampton, Oxford University, and the Natural History Museum attempted to correct the record for Raphus cucullatus. According to an accompanying August 16 announcement, the paper represents “the most comprehensive review of the taxonomy of the Dodo and its closest relative, the Rodriguez Island Solitaire.” Neil Gostling, the study’s supervising author and University of Southampton professor of evolution and paleobiology, argues that most people’s idea of the dodo isn’t simply inaccurate—it ignores the larger issues behind its extinction.

“If you picture the dodo, you picture… this dumpy, slightly stupid bird that kind of deserved to go extinct. That’s not the case,” Gostling says in a university video profile. “It was neither fat nor stupid, it was adapted to the ecosystem in the isle of Mauritius that it had been living in for millions of years.”

What the dodo and its sister species, the Rodrigues solitaire, were not adapted for, however, was the violent, colonizing force of modern society. Dutch sailors first encountered the dodo in 1598 after arriving on the island, located roughly 705 miles east of Madagascar in the Indian Ocean. Having evolved without any significant predators, the birds had no instinctual wariness of humans, making them easy prey for both hungry ship crews and international trade. In less than a century, the dodo was wiped out—but not due to their popularity on menus or in zoos.

The dodo’s main enemies weren’t humans themselves, but everything they brought with them while establishing a provisioning port for the Dutch East India Company on Mauritius. Livestock such as pigs trampled the ground birds’ nests, while rats devoured their eggs and small chicks. Meanwhile, dogs, cats, and other invasive animals preyed on the birds themselves while also competing for the island’s limited food sources. By 1662, the dodo was done. Barely a century later, the Rodrigues solitaire followed it into extinction. And with just 64 years of human documentation of the former, it didn’t take long before bird fact blended with bird fiction.

“The dodo was the first living thing that was recorded as being present and then disappeared,” Gostling said, adding that before their extinction, “it hadn’t been thought possible” that human beings could exert so much influence on the environment.

By the early 19th century, some circles even considered both the dodo and the solitaire “mythological beasts,” added Mark Young, a University of Southampton professor specializing in human transport and paper lead author. During the 1800’s, however, Victorian scientists finally proved both bird species did once exist. But over time, the dodo’s image transitioned largely from an emblem of humanity’s often disastrous environmental impact, to an inaccurate, misunderstood example of “survival of the fittest.” 

[Related: Dodos were actually not that dumb.]

Meanwhile, more than 400 years of subsequent taxonomic confusion led experts to debate just how many dodo and solitaire species originally existed—some biologists argued in favor of three separate variations, while others contended as many as five once roamed the region. These possibilities included the Nazarene Dodo, the White Dodo, and the White Solitaire, among others.

But after a painstaking review of four centuries’ worth of scientific writings and physical remains—including the only surviving dodo soft tissue—Gostling, Young, and their teammates believe they have some answers. Most notably, there were only ever the two species, dodo and solitaire, and they belonged to the columbid family along with pigeons and doves.

As for its “dumpy” reputation, a closer look at its anatomy indicates the dodo was far from a clumsy, slow-moving bird. Skeletal remains studied by the team show that the dodo possessed a tendon in its leg almost the same diameter as the bone itself. This feature can be found today in other avian species known for their speed and climbing agility, indicating the dodo was actually an incredibly fast and active animal.

“Even four centuries later, we have so much to learn about these remarkable birds,” Young said. “The few written accounts of live Dodos say it was a fast-moving animal that loved the forest.”

​​[Related: Is de-extinction only a pipette dream?]

Researchers believe that further reevaluations of the dodo and the solitaire will not only help dispel inaccurate myths, but refocus their legacies. Ultimately, their extinction isn’t the result of any evolutionary failings, but rather the effects of humans when we are at our most environmentally reckless. 

“Dodos held an integral place in their ecosystems. If we understand them, we might be able to support ecosystem recovery in Mauritius, perhaps starting to undo the damage that began with the arrival of humans nearly half a millennium ago,” Gostling explained, adding that, “There are no other birds alive today like these two species of giant ground dove.”

The post The dodo was faster and smarter than you think appeared first on Popular Science.

As the insect sentinels of summer, fireflies use their glowing bellies to communicate to other fireflies. Males from the species Abscondita terminalis use multi-pulse flashes with both of their lanterns to attract females. The females use single-pulse flashes with their one lantern. However, a new study found that some spiders may have decoded this signal and are using it to its advantage. This mimicry is detailed in a study published August 19 in the journal Current Biology.

When orb-weaving spiders (Araneus ventricosus) trap male fireflies in their webs, they manipulate the flashing signals to mimic the typical flashes made by female fireflies. These feigned flashes then lure other males into the web where they become the spider’s next meal. However, we still don’t know if the spider’s venom or a bite itself is manipulating the firefly’s signal. 

[Related: A new theory on why fireflies glow—and why they need help.]

The discovery arose after Xinhua Fu, a study co-author and entomologist at Huazhong Agricultural University in China observed several male fireflies entangled in orb-weaving spider webs while working in the field. He rarely saw a female firefly trapped in a web and additional field trips revealed this sexually skewed pattern. Fu hypothesized that the spiders may be somehow manipulating the fireflies’ behavior to attract others. 

To test this hypothesis that the spiders are manipulating the firefly’s signal, he recruited behavioral ecologists Daiqin Li and Shichang Zhang from Hubei University. The team conducted field experiments where they observed the firefly signals and spider behavior. The observations showed that the spider’s web captured male fireflies more often when the spider was there, compared to when it was away from the web. 

After further analysis, they found that the signals created by male fireflies in webs with spiders present looked more like the signals made by free flying females. The trapped males used single-pulse signals that use only one lantern and not both. 

Interestingly, the ensnared male fireflies very rarely lured other males when they were alone in the web and the spider was not around. This suggests that the males were not altering their flashes as a kind of distress signal. The team believes that the spiders are altering the firefly’s signal.

“While the eyes of orb-web spiders typically support limited spatial acuity, they rely more on temporal acuity rather than spatial acuity for discriminating flash signals,” Li said in a statement. “Upon detecting the bioluminescent signals of ensnared male fireflies, the spider deploys a specialized prey-handling procedure involving repeated wrap-bite attacks.”

[Related: Spider glue might evolve faster than the spiders themselves.]

According to the team, the experiment reveals that some animals are capable of using indirect yet dynamic signaling to go after a very specific category of prey in nature. The team also believes that there could be many other undescribed examples of this kind of mimicry in nature waiting to be uncovered. Predators could be using sound, pheromones, or other means, and not just visual signals to fool their prey. This deceptive ability is not exclusive to the animal kingdom either. The South African daisy appears to trick flies into mating with it and depositing pollen. 

“We propose that in response to seeing the ensnared male fireflies’ bioluminescent signals, the spider deployed a specialized-prey handling procedure based on repeated wrap bite attacks,” the team wrote in the study. “We also hypothesize that the male firefly’s neurotransmitters may generate a female-like flashing pattern.”

However, additional study is needed to determine what exactly is changing in the trapped firefly’s flashing pattern.

The post Spiders may be hacking firefly signals to trap dinner appeared first on Popular Science.

Like many children of his generation, raised on a steady diet of Jurassic Park and its sequels, Sébastien Calvignac-Spencer wanted to be a paleontologist when he grew up. Unlike most, he came close. Rather than digging for fossilized bones in the dirt, however, he paws through objects in natural history museums and medical collections for old biological specimens from which he can extract the...

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Two years ago, Sarah Shomstein realized she didn’t have a mind’s eye. The vision scientist was sitting in a seminar room, listening to a scientific talk, when the presenter asked the audience to imagine an apple. Shomstein closed her eyes and did so. Then, the presenter asked the crowd to open their eyes and rate how vividly they saw the apple in their mind. Saw the apple? Shomstein was confused.

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Two years ago, Sarah Shomstein realized she didn’t have a mind’s eye. The vision scientist was sitting in a seminar room, listening to a scientific talk, when the presenter asked the audience to imagine an apple. Shomstein closed her eyes and did so. Then, the presenter asked the crowd to open their eyes and rate how vividly they saw the apple in their mind. Saw the apple? Shomstein was confused.

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Amanda Randles wants to copy your body. If the computer scientist had her way, she’d have enough data — and processing power — to effectively clone you on her computer, run the clock forward, and see what your coronary arteries or red blood cells might do in a week. Fully personalized medical simulations, or “digital twins,” are still beyond our abilities, but Randles has pioneered computer models...

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Enlarge / Muscle atrophy is a known hazard of spending time on the International Space Station. (credit: NASA)

Muscle-on-chip systems are three-dimensional human muscle cell bundles cultured on collagen scaffolds. A Stanford University research team sent some of these systems to the International Space Station to study the muscle atrophy commonly observed in astronauts.

It turns out that space triggers processes in human muscles that eerily resemble something we know very well: getting old. “We learned that microgravity mimics some of the qualities of accelerated aging,” said Ngan F. Huang, an associate professor at Stanford who led the study.

Space-borne bioconstructs

“This work originates from our lab’s expertise in regenerative medicine and tissue engineering. We received funding to do a tissue engineering experiment on the ISS, which really helped us embark on this journey, and became curious how microgravity affects human health,” said Huang. So her team got busy designing the research equipment needed to work onboard the space station. The first step was building the muscle-on-chip systems.

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Penguins can’t fly. And while their wings may seem to be purely decorative, these appendages actually play a larger role in their evolutionary history. A fossil penguin species named Pakudyptes hakataramea bridges a gap between penguins that have gone extinct and those living today. Some of its bones show how these wings evolved to help penguins become such speedy swimmers. The findings are described in a study published July 31 in the Journal of the Royal Society of New Zealand. 

Pakudyptes lived in present-day New Zealand’s South Island about 24 million years ago. It was very small, roughly the same size as the little blue penguin–or kororā living today. At only 9.8 inches tall and 2.2 pounds, Pakudyptes are among the smallest known penguin species to ever live on Earth. 

[Related: This human-sized penguin isn’t even the largest ancient penguin we know about.]

Interestingly, Pakudyptes did have the physical adaptations that allowed them to dive into the water, despite being such an early penguin species. In the study, a team of scientists from the University of Otago in New Zealand, and Japan’s Ashoro Museum of Paleontology, Okayama University of Science, and Osaka University examined three bones. The humerus, femur, and ulna were discovered during several field trips in 1987 by the late paleontologist Ewan Fordyce in the Hakataramea Valley, in the Canterbury region of the South Island. 

They found that Pakudyptes fills in a morphological gap between modern and fossil penguins who are now extinct.

“In particular, the shape of the wing bones differed greatly, and the process by which penguin wings came to have their present form and function remained unclear,” study co-author and Ashoro Museum of Paleontology paleontologist Tatsuro Ando said in a statement. 

The humerus and ulna bones show how the penguins’ wings have evolved. 

“Surprisingly, while the shoulder joints of the wing of Pakudyptes were very close to the condition of the present-day penguin, the elbow joints were very similar to those of older types of fossil penguins,” said Ando. “Pakudyptes is the first fossil penguin ever found with this combination, and it is the ‘key’ fossil to unlocking the evolution of penguin wings.”

Otago’s Faculty of Dentistry analyzed the fossil’s internal bone structure alongside data on living penguins from the Okayama University of Science. They found that Pakudyptes had microanatomical features that suggest they could dive. Modern penguins are well known for their excellent swimming abilities. Their bullet-like swimming skills are largely due to the dense, thick bones that add to their buoyancy during diving.

In Pakudyptes, the bone cortex was reasonably thick. However, the medullary cavity–which contains bone marrow–was open. This is similar to the living little blue penguin, which usually swims in shallow waters. 

Pakudyptes’ diving and swimming likely comes down to the distinctive combination of its bones. The humerus and ulna show spots for attachment of muscles and ligaments, which reveal how the wings were used to swim and move underwater. 

[Related: Poop stains reveal four previously unknown Emperor penguin colonies.]

While no longer living, fossil penguins were usually large. Some could reach about 4.5 feet or even 6 feet tall, compared to today’s Emperor penguins that clock in at about three to four feet.

“Penguins evolved rapidly from the Late Oligocene to Early Miocene and Pakudyptes is an important fossil from this period,” study co-author Carolina Loch from Otago’s Faculty of Dentistry said in a statement. “Its small size and unique combination of bones may have contributed to the ecological diversity of modern penguins.”

The post Tiny fossil reveals when penguins evolved their surprisingly useful wings appeared first on Popular Science.

A newly discovered extinct mollusk species that skulked along the ocean floor half a billion years ago is offering new insights into the early days of this diverse group of animals. Fossils from Shishania aculeata indicate that some early mollusks were flat, armored, slug-like creatures that didn’t have the signature shells we see on today’s snails and bivalves. This species was also covered with hollow cone-shaped spines called sclerites. The findings are detailed in a study published August 1 in the journal Science. 

Shishania was discovered thanks to some well-preserved fossils uncovered in the Yunnan Province in southern China. The newly named species dates back to the early Cambrian Period–roughly 514 million years ago. The specimens of Shishania that the team studied are a few centimeters long and the spiky cones are made of chitin. This crunchy material is also found in the shells of modern insects, crabs, and even some mushrooms.  

The fossils that were preserved upside down, indicates that it likely had a muscular foot similar to a slug. Shishania would have used that leg to creep around the seafloor. Unlike most mollusks, it lacked a shell that covered its body. 

[Related: Experience the uncomfortable weirdness of a snail eating fruit.]

Living mollusks come in a wide array of forms–snails, clams, and highly intelligent cephalopods like squids and octopuses. All of this biodiversity developed very quickly during the Cambrian Explosion. This event about 530 million years ago was when all of the major groups of animals were rapidly diversifying. However, due to this accelerated pace of change, few fossils have been left behind to tell the story of early mollusk evolution. The team believes that Shishania represents a very early stage in molluscan evolution.

“Trying to unravel what the common ancestor of animals as different as a squid and oyster looked like is a major challenge for evolutionary biologists and paleontologists–one that can’t be solved by studying only species alive today,” study co-author and University of Oxford in England paleontologist Luke Parry said in a statement. “Shishania gives us a unique view into a time in mollusc evolution for which we have very few fossils, informing us that the very earliest mollusc ancestors were armored spiny slugs, prior to the evolution of the shells that we see in modern snails and clams.”

Shishania’s body was made of soft tissues that typically don’t preserve well in the fossil record. This made the specimens a bit challenging to study, since several were poorly preserved.

“At first I thought that the fossils, which were only about the size of my thumb, were not noticeable, but I saw under a magnifying glass that they seemed strange, spiny, and completely different from any other fossils that I had seen,” Guangxu Zhang, a study co-author and recent PhD graduate from Yunnan University in China who discovered the fossils, said in a statement. “I called it ‘the plastic bag’ initially because it looks like a rotting little plastic bag. When I found more of these fossils and analyzed them in the lab I realized that it was a mollusc.”

Shishania’s spines show an internal system of canals that are less than one hundredth of a millimeter in diameter. The cones were secreted at their base by microvilli–tiny protrusions of cells that increase surface area. Microvilli are found on the human tongue and in the intestines where they help the body absorb food.

“We found microscopic details inside the conical spines covering the body of Shishania that show how they were secreted in life,” said Parry. “This sort of information is incredibly rare, even in exceptionally preserved fossils.”

The team likens Shishania’s method of secreting hard parts to a natural 3D printer that can change its body parts depending on what the animal needs. This method allows several invertebrates to secrete hard parts that do everything from providing defense to helping it scoot around. 

[Related: This taco-shaped critter is a big (evolutionary) deal.]

Chitons–the hard spines and bristles in some modern mollusks–are made of the mineral calcium carbonate instead of the organic chitin that is in Shishania. Similar chitinous bristles can be found in some more obscure groups of animals including brachiopods and bryozoans. These animals along with mollusks and annelids (modern earthworms and their relatives) form the group Lophotrochozoa.
“Shishania tells us that the spines and spicules we see in chitons and aplacophoran mollusks today actually evolved from organic sclerites like those of annelids,” said Parry. “These animals are very different from one another today and so fossils like Shishania tell us what they looked like deep in the past, soon after they had diverged from common ancestors.”

The post A ‘rotting little plastic bag’ was actually a 514 million-year-old fossil appeared first on Popular Science.

While humans won’t be regenerating entire limbs like sea stars, some new genetic work with fruit flies has yielded some surprising results. A team from the University of Tokyo found that certain genes from simple organisms that help them regenerate body parts and tissues can be transferred into other animals. These genes then suppressed an intestinal issue in the flies and could potentially reveal some new mechanisms for rejuvenation in more complex organisms. The findings are detailed in a study published August 1 in the journal BMC Biology.

[Related: These fingernail-sized jellyfish can regenerate tentacles—but how?]

Some animals including jellyfish and flatworms can regenerate their whole bodies. While scientists still don’t really know how, there are possibly specific genes that allow regeneration. These same genes may also maintain long-term stem cell functions.

Stem cells can divide and renew themselves over a long period of time and are kind of like a skeleton key. While they aren’t necessarily specialized, they can potentially become more specialized cells, including blood cells and brain cells, over time. Mammals and insects who have very limited regenerative skills may have lost these genes over the course of evolution. 

“It is unclear whether reintroducing these regeneration-associated genes in low regenerative animals could affect their regeneration and aging processes,” study co-author and University of Tokyo Graduate School of Pharmaceutical Sciences biologist Yuichiro Nakajima said in a statement.

In this new study, Nakajima and the team focused on the group of genes that is unique to animals with high regenerative capacity like flatworms. These genes are called HRJDs, or highly regenerative species-specific JmjC domain-encoding genes. They transferred the HRJDs into the fruit fly (Drosophila melanogaster) and tracked their health with a blue dye. They nicknamed the fly Smurf, thanks to this hue. 

Initially, they hoped that these HRJD-boosted fruit flies would regenerate tissue if injured. This didn’t happen. However, the team had a fruit fly intestine expert Hiroki Nagai onboard, who noticed something else. There were some novel phenotypes–or the characteristics like eye color or hair color that comes from a specific gene.  

“HRJDs promoted greater intestinal stem cell division, whilst also suppressing intestinal cells that were mis-differentiating, or going wrong in aged flies,” said Nakajima. 

This is different to how antibiotics may suppress the mis-differentiated intestinal cells, but suppress intestinal stem cell division. 

[Related: Hydras can regrow their heads. Scientists want to know how they do it.]

“For this reason, HRJDs had a measurable effect on the lifespans of fruit flies, which opens the door, or at least provides clues, for the development of new anti-aging strategies,” said  Nakajima. “After all, human and insect intestines have surprisingly much in common on a cellular level.”

Fruit flies are famous test subjects in biological research. They share 75 percent of the genes that cause diseases in humans, reproduce quickly, and their genetic code is fairly easy to change. However, even with their relatively short lives and rapid-fire reproduction and maturating rates, it still took about two months to study their full aging process. 

In future studies, the team would like to take a closer look at how HRJD’s work on a molecular level. 

“Details of the molecular workings of HRJDs are still unresolved. And it’s unclear whether they work alone or in combination with some other component,” said Nakajima. “Therefore, this is just the start of the journey, but we know now that our modified fruit flies can serve as a valuable resource to uncover unprecedented mechanisms of stem cell rejuvenation in the future. In humans, intestinal stem cells decrease in activity with age, so this research is a promising avenue for stem cell-based therapies.”

The post Swapping genes can help fruit flies regenerate cells appeared first on Popular Science.

The universe seems like it should be unfathomably complex. How then is science able to crack fundamental questions about nature and life? Scientists and philosophers alike have often commented on the “unreasonable” success of mathematics at describing the universe. That success has helped science probe some profound mysteries — but as the physicist Nigel Goldenfeld points out, it also helps that...

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Each summer, like clockwork, millions of beech trees throughout Europe sync up, tuning their reproductive physiology to one another. Within a matter of days, the trees produce all the seeds they’ll make for the year, then release their fruit onto the forest floor to create a new generation and feed the surrounding ecosystem. It’s a reproductive spectacle known as masting that’s common to many tree...

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During traumatic periods and their aftermath, our brains can fall into habitual ways of thinking that may be helpful in the short run but become maladaptive years later. For the brain to readjust to new situations later in life, it needs to be restored to the malleable state it was in when the habits first formed. That is exactly what Gül Dölen, a neuroscientist and psychiatric researcher at the...

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Researchers recently reported the discovery of a natural protein, named Balon, that can bring a cell’s production of new proteins to a screeching halt. Balon was found in bacteria that hibernate in Arctic permafrost, but it also seems to be made by many other organisms and may be an overlooked mechanism for dormancy throughout the tree of life. For most life forms, the ability to shut oneself off...

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A visit to a peat bog will make you rethink everything you know about the surface of our planet. A bog is land, sort of, but not in the solid-ground sense you’re used to. If you try walking across one’s surface, you may feel the soft organic muck known as peat undulate beneath you — or you may sink into it yourself. From the surface, it’s hard to know whether the waterlogged peat extends 3 feet...

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For decades, the best drug therapies for treating depression, like SSRIs, have been based on the idea that depressed brains don’t have enough of the neurotransmitter serotonin. Yet for almost as long, it’s been clear that simplistic theory is wrong. Recent research into the true causes of depression is finding clues in other neurotransmitters and the realization that the brain is much more...

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Enlarge / The spliceosome is a large complex of proteins and RNAs. (credit: NCBI)

Almost 1,500 genes have been implicated in intellectual disabilities; yet for most people with such disabilities, genetic causes remain unknown. Perhaps this is in part because geneticists have been focusing on the wrong stretches of DNA when they go searching. To rectify this, Ernest Turro—a biostatistician who focuses on genetics, genomics, and molecular diagnostics—used whole genome sequencing data from the 100,000 Genomes Project to search for areas associated with intellectual disabilities.

His lab found a genetic association that is the most common one yet to be associated with neurodevelopmental abnormality. And the gene they identified doesn’t even make a protein.

Trouble with the spliceosome

Most genes include instructions for how to make proteins. That’s true. And yet human genes are not arranged linearly—or rather, they are arranged linearly, but not contiguously. A gene containing the instructions for which amino acids to string together to make a particular protein—hemoglobin, insulin, serotonin, albumin, estrogen, whatever protein you like—is modular. It contains part of the amino acid sequence, then it has a chunk of DNA that is largely irrelevant to that sequence, then a bit more of the protein’s sequence, then another chunk of random DNA, back and forth until the end of the protein. It’s as if each of these prose paragraphs were separated by a string of unrelated letters (but not a meaningful paragraph from a different article).

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Out of all the cells in the body, oocytes are the most patient. The immature egg cells form inside a female’s body when she’s still a fetus in her mother’s womb, and then they wait in a quiescent state for years, if not decades. Cocooned inside ovaries, they pause, neither dividing nor replicating their DNA, so that one day they may pass along pristinely preserved genetic information to the next...

Source

Proteins are the molecular machines that sustain every cell and organism, and knowing what they look like will be critical to untangling how they function normally and malfunction in disease. Now researchers have taken a huge stride toward that goal with the development of new machine learning algorithms that can predict the folded shapes of not only proteins but other biomolecules with...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

Proteins are the molecular machines that sustain every cell and organism, and knowing what they look like will be critical to untangling how they function normally and malfunction in disease. Now researchers have taken a huge stride toward that goal with the development of new machine learning algorithms that can predict the folded shapes of not only proteins but other biomolecules with...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

Enlarge / The Colorado River toad, also known as the Sonoran Desert Toad. (credit: Mark Newman)

It is becoming increasingly accepted that classic psychedelics like LSD, psilocybin, ayahuasca, and mescaline can act as antidepressants and anti-anxiety treatments in addition to causing hallucinations. They act by binding to a serotonin receptor. But there are 14 known types of serotonin receptors, and most of the research into these compounds has focused on only one of them—the one these molecules like, called 5-HT2A. (5-HT, short for 5-hydroxytryptamine, is the chemical name for serotonin.)

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, secretes a psychedelic compound that likes to bind to a different serotonin receptor subtype called 5-HT1A. And that difference may be the key to developing an entirely distinct class of antidepressants.

Uncovering novel biology

Like other psychedelics, the one the toad produces decreases depression and anxiety and induces meaningful and spiritually significant experiences. It has been used clinically to treat vets with post-traumatic stress disorder and is being developed as a treatment for other neurological disorders and drug abuse. 5-HT1A is a validated therapeutic target, as approved drugs, including the antidepressant Viibryd and the anti-anxiety med Buspar, bind to it. But little is known about how psychedelics engage with this receptor and which effects it mediates, so Daniel Wacker’s lab decided to look into it.

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Enlarge / Xorides praecatorius is a parasitoid wasp. (credit: TorriPhoto via Getty)

If you puncture the ovary of a wasp called Microplitis demolitor, viruses squirt out in vast quantities, shimmering like iridescent blue toothpaste. “It’s very beautiful, and just amazing that there’s so much virus made in there,” says Gaelen Burke, an entomologist at the University of Georgia.

M. demolitor  is a parasite that lays its eggs in caterpillars, and the particles in its ovaries are “domesticated” viruses that have been tuned to persist harmlessly in wasps and serve their purposes. The virus particles are injected into the caterpillar through the wasp’s stinger, along with the wasp’s own eggs. The viruses then dump their contents into the caterpillar’s cells, delivering genes that are unlike those in a normal virus. Those genes suppress the caterpillar’s immune system and control its development, turning it into a harmless nursery for the wasp’s young.

The insect world is full of species of parasitic wasps that spend their infancy eating other insects alive. And for reasons that scientists don’t fully understand, they have repeatedly adopted and tamed wild, disease-causing viruses and turned them into biological weapons. Half a dozen examples already are described, and new research hints at many more.

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Amazon’s Fallout TV show, which premiered last month, was a big success and has already been greenlit for a second season. However, new data reveals that it is likely Amazon’s biggest show ever and was also one of the most watched things in April, beating out shows like Bluey, Grey’s Anatomy, and NCIS.

Read more...

Every organism visible to the naked eye is a mass of genetically identical cells. Each of these multicellular creatures started as a single cell that divided countless times to produce its body. And while each cell contains the same genome, they express their DNA in a variety of ways, giving rise to specialized cells and tissues that perform different roles, such as skin, liver or immune cells.

Source

In 2022, researchers at the Bee Sensory and Behavioral Ecology Lab at Queen Mary University of London observed bumblebees doing something remarkable: The diminutive, fuzzy creatures were engaging in activity that could only be described as play. Given small wooden balls, the bees pushed them around and rotated them. The behavior had no obvious connection to mating or survival, nor was it rewarded...

Source

Ishmail Abdus-Saboor has been fascinated by the variety of the natural world since he was a boy growing up in Philadelphia. The nature walks he took under the tutelage of his third grade teacher, Mr. Moore, entranced him. “We got to interact and engage with wildlife and see animals in their native environment,” he recalled. Abdus-Saboor also brought a menagerie of creatures — cats, dogs, lizards...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

In 2022, researchers at the Bee Sensory and Behavioral Ecology Lab at Queen Mary University of London observed bumblebees doing something remarkable: The diminutive, fuzzy creatures were engaging in activity that could only be described as play. Given small wooden balls, the bees pushed them around and rotated them. The behavior had no obvious connection to mating or survival, nor was it rewarded...

Source

Ishmail Abdus-Saboor has been fascinated by the variety of the natural world since he was a boy growing up in Philadelphia. The nature walks he took under the tutelage of his third grade teacher, Mr. Moore, entranced him. “We got to interact and engage with wildlife and see animals in their native environment,” he recalled. Abdus-Saboor also brought a menagerie of creatures — cats, dogs, lizards...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

It can be hard to tell, at first, when a cell is on the verge of self-destruction. It appears to be going about its usual business, transcribing genes and making proteins. The powerhouse organelles called mitochondria are dutifully churning out energy. But then a mitochondrion receives a signal, and its typically placid proteins join forces to form a death machine. They slice through the cell with...

Source

Biologists have often wondered what would happen if they could rewind the tape of life’s history and let evolution play out all over again. Would lineages of organisms evolve in radically different ways if given that opportunity? Or would they tend to evolve the same kinds of eyes, wings and other adaptive traits because their previous evolutionary histories had already sent them down certain...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

There is vast opportunity for nanoscale innovation to transform the world in positive ways — expressed MIT.nano Director Vladimir Bulović as he posed two questions to attendees at the start of the inaugural Nano Summit: “Where are we heading? And what is the next big thing we can develop?”

“The answer to that puts into perspective our main purpose — and that is to change the world,” Bulović, the Fariborz Maseeh Professor of Emerging Technologies, told an audience of more than 325 in-person and 150 virtual participants gathered for an exploration of nano-related research at MIT and a celebration of MIT.nano’s fifth anniversary.

Over a decade ago, MIT embarked on a massive project for the ultra-small — building an advanced facility to support research at the nanoscale. Construction of MIT.nano in the heart of MIT’s campus, a process compared to assembling a ship in a bottle, began in 2015, and the facility launched in October 2018.

Fast forward five years: MIT.nano now contains nearly 170 tools and instruments serving more than 1,200 trained researchers. These individuals come from over 300 principal investigator labs, representing more than 50 MIT departments, labs, and centers. The facility also serves external users from industry, other academic institutions, and over 130 startup and multinational companies. And in 2022, MIT.nano's home — Building 12 — was named in honor of Lisa T. Su ’90, SM ’91, PhD ’94, chief executive officer and chair of the Board of Directors of AMD.

A cross section of these faculty and researchers joined industry partners and MIT community members to kick off the first Nano Summit, which is expected to become an annual flagship event for MIT.nano and its industry consortium. Held on Oct. 24, the inaugural conference was co-hosted by the MIT Industrial Liaison Program.

Six topical sessions highlighted recent developments in quantum science and engineering, materials, advanced electronics, energy, biology, and immersive data technology. The Nano Summit also featured startup ventures and an art exhibition.

Watch the videos here.

Seeing and manipulating at the nanoscale — and beyond

“We need to develop new ways of building the next generation of materials,” said Frances Ross, the TDK Professor in Materials Science and Engineering (DMSE). “We need to use electron microscopy to help us understand not only what the structure is after it’s built, but how it came to be. I think the next few years in this piece of the nano realm are going to be really amazing.”

Speakers in the session “The Next Materials Revolution,” chaired by MIT.nano co-director for Characterization.nano and associate professor in DMSE James LeBeau, highlighted areas in which cutting-edge microscopy provides insights into the behavior of functional materials at the nanoscale, from anti-ferroelectrics to thin-film photovoltaics and 2D materials. They shared images and videos collected using the instruments in MIT.nano’s characterization suites, which were specifically designed and constructed to minimize mechanical-vibrational and electro-magnetic interference.

Later, in the “Biology and Human Health” session chaired by Boris Magasanik Professor of Biology Thomas Schwartz, biologists echoed the materials scientists, stressing the importance of the ultra-quiet, low-vibration environment in Characterization.nano to obtain high-resolution images of biological structures.

“Why is MIT.nano important for us?” asked Schwartz. “An important element of biology is to understand the structure of biology macromolecules. We want to get to an atomic resolution of these structures. CryoEM (cryo-electron microscopy) is an excellent method for this. In order to enable the resolution revolution, we had to get these instruments to MIT. For that, MIT.nano was fantastic.”

Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences, shared CryoEM images from her lab’s work, followed by biology Associate Professor Joey Davis who spoke about image processing. When asked about the next stage for CryoEM, Davis said he’s most excited about in-situ tomography, noting that there are new instruments being designed that will improve the current labor-intensive process.

To chart the future of energy, chemistry associate professor Yogi Surendranath is also using MIT.nano to see what is happening at the nanoscale in his research to use renewable electricity to change carbon dioxide into fuel.

“MIT.nano has played an immense role, not only in facilitating our ability to make nanostructures, but also to understand nanostructures through advanced imaging capabilities,” said Surendranath. “I see a lot of the future of MIT.nano around the question of how nanostructures evolve and change under the conditions that are relevant to their function. The tools at MIT.nano can help us sort that out.”

Tech transfer and quantum computing

The “Advanced Electronics” session chaired by Jesús del Alamo, the Donner Professor of Science in the Department of Electrical Engineering and Computer Science (EECS), brought together industry partners and MIT faculty for a panel discussion on the future of semiconductors and microelectronics. “Excellence in innovation is not enough, we also need to be excellent in transferring these to the marketplace,” said del Alamo. On this point, panelists spoke about strengthening the industry-university connection, as well as the importance of collaborative research environments and of access to advanced facilities, such as MIT.nano, for these environments to thrive.

The session came on the heels of a startup exhibit in which eleven START.nano companies presented their technologies in health, energy, climate, and virtual reality, among other topics. START.nano, MIT.nano’s hard-tech accelerator, provides participants use of MIT.nano’s facilities at a discounted rate and access to MIT’s startup ecosystem. The program aims to ease hard-tech startups’ transition from the lab to the marketplace, surviving common “valleys of death” as they move from idea to prototype to scaling up.

When asked about the state of quantum computing in the “Quantum Science and Engineering” session, physics professor Aram Harrow related his response to these startup challenges. “There are quite a few valleys to cross — there are the technical valleys, and then also the commercial valleys.” He spoke about scaling superconducting qubits and qubits made of suspended trapped ions, and the need for more scalable architectures, which we have the ingredients for, he said, but putting everything together is quite challenging.

Throughout the session, William Oliver, professor of physics and the Henry Ellis Warren (1894) Professor of Electrical Engineering and Computer Science, asked the panelists how MIT.nano can address challenges in assembly and scalability in quantum science.

“To harness the power of students to innovate, you really need to allow them to get their hands dirty, try new things, try all their crazy ideas, before this goes into a foundry-level process,” responded Kevin O’Brien, associate professor in EECS. “That’s what my group has been working on at MIT.nano, building these superconducting quantum processors using the state-of-the art fabrication techniques in MIT.nano.”

Connecting the digital to the physical

In his reflections on the semiconductor industry, Douglas Carlson, senior vice president for technology at MACOM, stressed connecting the digital world to real-world application. Later, in the “Immersive Data Technology” session, MIT.nano associate director Brian Anthony explained how, at the MIT.nano Immersion Lab, researchers are doing just that.

“We think about and facilitate work that has the human immersed between hardware, data, and experience,” said Anthony, principal research scientist in mechanical engineering. He spoke about using the capabilities of the Immersion Lab to apply immersive technologies to different areas — health, sports, performance, manufacturing, and education, among others. Speakers in this session gave specific examples in hardware, pediatric health, and opera.

Anthony connected this third pillar of MIT.nano to the fab and characterization facilities, highlighting how the Immersion Lab supports work conducted in other parts of the building. The Immersion Lab’s strength, he said, is taking novel work being developed inside MIT.nano and bringing it up to the human scale to think about applications and uses.

Artworks that are scientifically inspired

The Nano Summit closed with a reception at MIT.nano where guests could explore the facility and gaze through the cleanroom windows, where users were actively conducting research. Attendees were encouraged to visit an exhibition on MIT.nano’s first- and second-floor galleries featuring work by students from the MIT Program in Art, Culture, and Technology (ACT) who were invited to utilize MIT.nano’s tool sets and environments as inspiration for art.

In his closing remarks, Bulović reflected on the community of people who keep MIT.nano running and who are using the tools to advance their research. “Today we are celebrating the facility and all the work that has been done over the last five years to bring it to where it is today. It is there to function not just as a space, but as an essential part of MIT’s mission in research, innovation, and education. I hope that all of us here today take away a deep appreciation and admiration for those who are leading the journey into the nano age.”

Biologists have often wondered what would happen if they could rewind the tape of life’s history and let evolution play out all over again. Would lineages of organisms evolve in radically different ways if given that opportunity? Or would they tend to evolve the same kinds of eyes, wings and other adaptive traits because their previous evolutionary histories had already sent them down certain...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

There is vast opportunity for nanoscale innovation to transform the world in positive ways — expressed MIT.nano Director Vladimir Bulović as he posed two questions to attendees at the start of the inaugural Nano Summit: “Where are we heading? And what is the next big thing we can develop?”

“The answer to that puts into perspective our main purpose — and that is to change the world,” Bulović, the Fariborz Maseeh Professor of Emerging Technologies, told an audience of more than 325 in-person and 150 virtual participants gathered for an exploration of nano-related research at MIT and a celebration of MIT.nano’s fifth anniversary.

Over a decade ago, MIT embarked on a massive project for the ultra-small — building an advanced facility to support research at the nanoscale. Construction of MIT.nano in the heart of MIT’s campus, a process compared to assembling a ship in a bottle, began in 2015, and the facility launched in October 2018.

Fast forward five years: MIT.nano now contains nearly 170 tools and instruments serving more than 1,200 trained researchers. These individuals come from over 300 principal investigator labs, representing more than 50 MIT departments, labs, and centers. The facility also serves external users from industry, other academic institutions, and over 130 startup and multinational companies. And in 2022, MIT.nano's home — Building 12 — was named in honor of Lisa T. Su ’90, SM ’91, PhD ’94, chief executive officer and chair of the Board of Directors of AMD.

A cross section of these faculty and researchers joined industry partners and MIT community members to kick off the first Nano Summit, which is expected to become an annual flagship event for MIT.nano and its industry consortium. Held on Oct. 24, the inaugural conference was co-hosted by the MIT Industrial Liaison Program.

Six topical sessions highlighted recent developments in quantum science and engineering, materials, advanced electronics, energy, biology, and immersive data technology. The Nano Summit also featured startup ventures and an art exhibition.

Watch the videos here.

Seeing and manipulating at the nanoscale — and beyond

“We need to develop new ways of building the next generation of materials,” said Frances Ross, the TDK Professor in Materials Science and Engineering (DMSE). “We need to use electron microscopy to help us understand not only what the structure is after it’s built, but how it came to be. I think the next few years in this piece of the nano realm are going to be really amazing.”

Speakers in the session “The Next Materials Revolution,” chaired by MIT.nano co-director for Characterization.nano and associate professor in DMSE James LeBeau, highlighted areas in which cutting-edge microscopy provides insights into the behavior of functional materials at the nanoscale, from anti-ferroelectrics to thin-film photovoltaics and 2D materials. They shared images and videos collected using the instruments in MIT.nano’s characterization suites, which were specifically designed and constructed to minimize mechanical-vibrational and electro-magnetic interference.

Later, in the “Biology and Human Health” session chaired by Boris Magasanik Professor of Biology Thomas Schwartz, biologists echoed the materials scientists, stressing the importance of the ultra-quiet, low-vibration environment in Characterization.nano to obtain high-resolution images of biological structures.

“Why is MIT.nano important for us?” asked Schwartz. “An important element of biology is to understand the structure of biology macromolecules. We want to get to an atomic resolution of these structures. CryoEM (cryo-electron microscopy) is an excellent method for this. In order to enable the resolution revolution, we had to get these instruments to MIT. For that, MIT.nano was fantastic.”

Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences, shared CryoEM images from her lab’s work, followed by biology Associate Professor Joey Davis who spoke about image processing. When asked about the next stage for CryoEM, Davis said he’s most excited about in-situ tomography, noting that there are new instruments being designed that will improve the current labor-intensive process.

To chart the future of energy, chemistry associate professor Yogi Surendranath is also using MIT.nano to see what is happening at the nanoscale in his research to use renewable electricity to change carbon dioxide into fuel.

“MIT.nano has played an immense role, not only in facilitating our ability to make nanostructures, but also to understand nanostructures through advanced imaging capabilities,” said Surendranath. “I see a lot of the future of MIT.nano around the question of how nanostructures evolve and change under the conditions that are relevant to their function. The tools at MIT.nano can help us sort that out.”

Tech transfer and quantum computing

The “Advanced Electronics” session chaired by Jesús del Alamo, the Donner Professor of Science in the Department of Electrical Engineering and Computer Science (EECS), brought together industry partners and MIT faculty for a panel discussion on the future of semiconductors and microelectronics. “Excellence in innovation is not enough, we also need to be excellent in transferring these to the marketplace,” said del Alamo. On this point, panelists spoke about strengthening the industry-university connection, as well as the importance of collaborative research environments and of access to advanced facilities, such as MIT.nano, for these environments to thrive.

The session came on the heels of a startup exhibit in which eleven START.nano companies presented their technologies in health, energy, climate, and virtual reality, among other topics. START.nano, MIT.nano’s hard-tech accelerator, provides participants use of MIT.nano’s facilities at a discounted rate and access to MIT’s startup ecosystem. The program aims to ease hard-tech startups’ transition from the lab to the marketplace, surviving common “valleys of death” as they move from idea to prototype to scaling up.

When asked about the state of quantum computing in the “Quantum Science and Engineering” session, physics professor Aram Harrow related his response to these startup challenges. “There are quite a few valleys to cross — there are the technical valleys, and then also the commercial valleys.” He spoke about scaling superconducting qubits and qubits made of suspended trapped ions, and the need for more scalable architectures, which we have the ingredients for, he said, but putting everything together is quite challenging.

Throughout the session, William Oliver, professor of physics and the Henry Ellis Warren (1894) Professor of Electrical Engineering and Computer Science, asked the panelists how MIT.nano can address challenges in assembly and scalability in quantum science.

“To harness the power of students to innovate, you really need to allow them to get their hands dirty, try new things, try all their crazy ideas, before this goes into a foundry-level process,” responded Kevin O’Brien, associate professor in EECS. “That’s what my group has been working on at MIT.nano, building these superconducting quantum processors using the state-of-the art fabrication techniques in MIT.nano.”

Connecting the digital to the physical

In his reflections on the semiconductor industry, Douglas Carlson, senior vice president for technology at MACOM, stressed connecting the digital world to real-world application. Later, in the “Immersive Data Technology” session, MIT.nano associate director Brian Anthony explained how, at the MIT.nano Immersion Lab, researchers are doing just that.

“We think about and facilitate work that has the human immersed between hardware, data, and experience,” said Anthony, principal research scientist in mechanical engineering. He spoke about using the capabilities of the Immersion Lab to apply immersive technologies to different areas — health, sports, performance, manufacturing, and education, among others. Speakers in this session gave specific examples in hardware, pediatric health, and opera.

Anthony connected this third pillar of MIT.nano to the fab and characterization facilities, highlighting how the Immersion Lab supports work conducted in other parts of the building. The Immersion Lab’s strength, he said, is taking novel work being developed inside MIT.nano and bringing it up to the human scale to think about applications and uses.

Artworks that are scientifically inspired

The Nano Summit closed with a reception at MIT.nano where guests could explore the facility and gaze through the cleanroom windows, where users were actively conducting research. Attendees were encouraged to visit an exhibition on MIT.nano’s first- and second-floor galleries featuring work by students from the MIT Program in Art, Culture, and Technology (ACT) who were invited to utilize MIT.nano’s tool sets and environments as inspiration for art.

In his closing remarks, Bulović reflected on the community of people who keep MIT.nano running and who are using the tools to advance their research. “Today we are celebrating the facility and all the work that has been done over the last five years to bring it to where it is today. It is there to function not just as a space, but as an essential part of MIT’s mission in research, innovation, and education. I hope that all of us here today take away a deep appreciation and admiration for those who are leading the journey into the nano age.”

In Cassandra Extavour’s office at Harvard University hangs a placard with a painted rainbow flag and a friendly invitation. “You are welcome here,” it reads. “I have it up because I think it’s important to let people see your identities, especially when those identities are not well represented,” explained Extavour, an evolutionary geneticist who in 2014 became the first Black woman to win tenure...

Source

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

There is vast opportunity for nanoscale innovation to transform the world in positive ways — expressed MIT.nano Director Vladimir Bulović as he posed two questions to attendees at the start of the inaugural Nano Summit: “Where are we heading? And what is the next big thing we can develop?”

“The answer to that puts into perspective our main purpose — and that is to change the world,” Bulović, the Fariborz Maseeh Professor of Emerging Technologies, told an audience of more than 325 in-person and 150 virtual participants gathered for an exploration of nano-related research at MIT and a celebration of MIT.nano’s fifth anniversary.

Over a decade ago, MIT embarked on a massive project for the ultra-small — building an advanced facility to support research at the nanoscale. Construction of MIT.nano in the heart of MIT’s campus, a process compared to assembling a ship in a bottle, began in 2015, and the facility launched in October 2018.

Fast forward five years: MIT.nano now contains nearly 170 tools and instruments serving more than 1,200 trained researchers. These individuals come from over 300 principal investigator labs, representing more than 50 MIT departments, labs, and centers. The facility also serves external users from industry, other academic institutions, and over 130 startup and multinational companies. And in 2022, MIT.nano's home — Building 12 — was named in honor of Lisa T. Su ’90, SM ’91, PhD ’94, chief executive officer and chair of the Board of Directors of AMD.

A cross section of these faculty and researchers joined industry partners and MIT community members to kick off the first Nano Summit, which is expected to become an annual flagship event for MIT.nano and its industry consortium. Held on Oct. 24, the inaugural conference was co-hosted by the MIT Industrial Liaison Program.

Six topical sessions highlighted recent developments in quantum science and engineering, materials, advanced electronics, energy, biology, and immersive data technology. The Nano Summit also featured startup ventures and an art exhibition.

Watch the videos here.

Seeing and manipulating at the nanoscale — and beyond

“We need to develop new ways of building the next generation of materials,” said Frances Ross, the TDK Professor in Materials Science and Engineering (DMSE). “We need to use electron microscopy to help us understand not only what the structure is after it’s built, but how it came to be. I think the next few years in this piece of the nano realm are going to be really amazing.”

Speakers in the session “The Next Materials Revolution,” chaired by MIT.nano co-director for Characterization.nano and associate professor in DMSE James LeBeau, highlighted areas in which cutting-edge microscopy provides insights into the behavior of functional materials at the nanoscale, from anti-ferroelectrics to thin-film photovoltaics and 2D materials. They shared images and videos collected using the instruments in MIT.nano’s characterization suites, which were specifically designed and constructed to minimize mechanical-vibrational and electro-magnetic interference.

Later, in the “Biology and Human Health” session chaired by Boris Magasanik Professor of Biology Thomas Schwartz, biologists echoed the materials scientists, stressing the importance of the ultra-quiet, low-vibration environment in Characterization.nano to obtain high-resolution images of biological structures.

“Why is MIT.nano important for us?” asked Schwartz. “An important element of biology is to understand the structure of biology macromolecules. We want to get to an atomic resolution of these structures. CryoEM (cryo-electron microscopy) is an excellent method for this. In order to enable the resolution revolution, we had to get these instruments to MIT. For that, MIT.nano was fantastic.”

Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences, shared CryoEM images from her lab’s work, followed by biology Associate Professor Joey Davis who spoke about image processing. When asked about the next stage for CryoEM, Davis said he’s most excited about in-situ tomography, noting that there are new instruments being designed that will improve the current labor-intensive process.

To chart the future of energy, chemistry associate professor Yogi Surendranath is also using MIT.nano to see what is happening at the nanoscale in his research to use renewable electricity to change carbon dioxide into fuel.

“MIT.nano has played an immense role, not only in facilitating our ability to make nanostructures, but also to understand nanostructures through advanced imaging capabilities,” said Surendranath. “I see a lot of the future of MIT.nano around the question of how nanostructures evolve and change under the conditions that are relevant to their function. The tools at MIT.nano can help us sort that out.”

Tech transfer and quantum computing

The “Advanced Electronics” session chaired by Jesús del Alamo, the Donner Professor of Science in the Department of Electrical Engineering and Computer Science (EECS), brought together industry partners and MIT faculty for a panel discussion on the future of semiconductors and microelectronics. “Excellence in innovation is not enough, we also need to be excellent in transferring these to the marketplace,” said del Alamo. On this point, panelists spoke about strengthening the industry-university connection, as well as the importance of collaborative research environments and of access to advanced facilities, such as MIT.nano, for these environments to thrive.

The session came on the heels of a startup exhibit in which eleven START.nano companies presented their technologies in health, energy, climate, and virtual reality, among other topics. START.nano, MIT.nano’s hard-tech accelerator, provides participants use of MIT.nano’s facilities at a discounted rate and access to MIT’s startup ecosystem. The program aims to ease hard-tech startups’ transition from the lab to the marketplace, surviving common “valleys of death” as they move from idea to prototype to scaling up.

When asked about the state of quantum computing in the “Quantum Science and Engineering” session, physics professor Aram Harrow related his response to these startup challenges. “There are quite a few valleys to cross — there are the technical valleys, and then also the commercial valleys.” He spoke about scaling superconducting qubits and qubits made of suspended trapped ions, and the need for more scalable architectures, which we have the ingredients for, he said, but putting everything together is quite challenging.

Throughout the session, William Oliver, professor of physics and the Henry Ellis Warren (1894) Professor of Electrical Engineering and Computer Science, asked the panelists how MIT.nano can address challenges in assembly and scalability in quantum science.

“To harness the power of students to innovate, you really need to allow them to get their hands dirty, try new things, try all their crazy ideas, before this goes into a foundry-level process,” responded Kevin O’Brien, associate professor in EECS. “That’s what my group has been working on at MIT.nano, building these superconducting quantum processors using the state-of-the art fabrication techniques in MIT.nano.”

Connecting the digital to the physical

In his reflections on the semiconductor industry, Douglas Carlson, senior vice president for technology at MACOM, stressed connecting the digital world to real-world application. Later, in the “Immersive Data Technology” session, MIT.nano associate director Brian Anthony explained how, at the MIT.nano Immersion Lab, researchers are doing just that.

“We think about and facilitate work that has the human immersed between hardware, data, and experience,” said Anthony, principal research scientist in mechanical engineering. He spoke about using the capabilities of the Immersion Lab to apply immersive technologies to different areas — health, sports, performance, manufacturing, and education, among others. Speakers in this session gave specific examples in hardware, pediatric health, and opera.

Anthony connected this third pillar of MIT.nano to the fab and characterization facilities, highlighting how the Immersion Lab supports work conducted in other parts of the building. The Immersion Lab’s strength, he said, is taking novel work being developed inside MIT.nano and bringing it up to the human scale to think about applications and uses.

Artworks that are scientifically inspired

The Nano Summit closed with a reception at MIT.nano where guests could explore the facility and gaze through the cleanroom windows, where users were actively conducting research. Attendees were encouraged to visit an exhibition on MIT.nano’s first- and second-floor galleries featuring work by students from the MIT Program in Art, Culture, and Technology (ACT) who were invited to utilize MIT.nano’s tool sets and environments as inspiration for art.

In his closing remarks, Bulović reflected on the community of people who keep MIT.nano running and who are using the tools to advance their research. “Today we are celebrating the facility and all the work that has been done over the last five years to bring it to where it is today. It is there to function not just as a space, but as an essential part of MIT’s mission in research, innovation, and education. I hope that all of us here today take away a deep appreciation and admiration for those who are leading the journey into the nano age.”

Retroviruses cannot replicate on their own — they must insert their genetic code into the DNA of a host and exploit the host cell's resources to make more copies of themselves, furthering infection. Some retroviruses only infect cells as they divide, when the nuclear envelope that protects the host's genetic material breaks down, making it easily accessible. HIV-1 is a type of retrovirus, called a lentivirus, that can infect non-dividing cells.

HIV-1 delivers its genome into the nucleus by packaging it into a large, cone-shaped structure called a capsid — but the exact mechanism has remained elusive for decades. Travel through the nuclear envelope occurs through, and is regulated by, nuclear pores, doughnut-shaped protein assemblies. Human cells have about 2,000 nuclear pores perforating the nuclear envelope. Some earlier evidence suggested that the capsid remains intact during its delivery into the nucleus — but this created a dimensional conundrum. The cone-shaped HIV-1 capsid is about 120 nanometers long and 60 nm wide — too large, researchers thought, to fit through the opening of the nuclear pore, measured at only 43 nm wide.

Members of the Schwartz Lab at MIT, in the Department of Biology, became interested in this question when a postdoc in the lab used cryo-electron tomography, slicing up sections of frozen cells to examine structures, to show that nuclear pores in the nuclear envelope are larger than 43nm. They deflate and shrink, it turns out, when removed from their native conditions. In native conditions, the nuclear pore complex is about 60nm wide — wide enough to accommodate the HIV-1 capsid.

Knowing that it could fit, a question remained: How can the capsid navigate the dense mesh of spaghetti-like proteins that act like a sieve in the nuclear pore channel? That spaghetti-like mesh allows small cargo to diffuse through, but prevents large cargo from entering unless it is escorted by proteins called nuclear transport receptors.

In an open-access paper published today in Nature, researchers present evidence that the HIV-1 capsid mimics the cell's transport receptors to traverse the nuclear pore.

To support that conclusion, the researchers showed three things in vitro: that an HIV-1 capsid can deliver cargo through a nuclear pore analog; that the capsid can interact with the sieve of proteins in the nuclear pore channel; and that the capsid targets the nuclear pore in the absence of native transport proteins.

Nuclear transport receptors escort large cargo through the nuclear pore by “batting away” the spaghetti-like mesh of proteins inside the channel — like someone holding your hand and guiding you across a crowded dance floor. The HIV-1 capsid interacts with the spaghetti-like proteins, but its purpose is more like a Trojan horse — the capsid encapsulates the viral cargo, protecting it from detection in the cytoplasm and as it enters the nuclear pore complex.

"What's really amazing about cells is that they are incredibly complex. What's really difficult about studying cells is that they are incredibly complex," jokes co-first author Erika Weiskopf, a graduate student in the Schwartz lab. "Biochemists are constantly trying to find ways to study their system in a simplified context, but still give it a flavor of cell biology."

To do that, the Schwartz lab collaborated with Dirk Görlich, the director of cellular logistics at the Max Planck Institute for Multidisciplinary Sciences. Görlich is a co-senior author on the paper with MIT’s Boris Magasanik Professor of Biology Thomas Schwartz. Görlich's lab has produced concentrated droplets of the spaghetti-like proteins found inside the nuclear pore, and those droplets allow and exclude cargo the same way a nuclear pore will. In experiments, fluorescently-labeled cargo did not enter the droplets, but fluorescently-labeled cargo packaged in an HIV-1 capsid was delivered. This indicated that the capsid could deliver cargo through a nuclear pore. 

Using a biophysical binding assay, the researchers also showed that the HIV-1 capsid interacts with the proteins inside the channel. Different spaghetti-like proteins are found in different channel sections, such as at the cytoplasmic side's entrance or only inside the channel; there are 10 such proteins in human cells. The capsid is a promiscuous binder — it can interact with all the spaghetti-like proteins found in the channel.

The capsid can target the nuclear pore complex even without the cell's transport receptors, indicating that it is not commandeering native transport receptors to find and enter the nuclear pore. The team used a classic assay in the nucleocytoplasmic transport field to collect this evidence: When cells are treated with digitonin, their membranes become porous. Everything in the cytoplasm will leak out of the cells, but the nuclear envelope will remain intact. Despite the absence of native proteins, the capsid was attracted to the nuclear pore complex, a behavior indicative of a nuclear transport receptor.

Although the capsid behaves like a nuclear transport receptor to penetrate the nuclear pore, it is fundamentally different. A transport receptor doesn't need to conceal material for delivery the way the capsid does to avoid detection.

These findings open new lines of inquiry for what the nuclear pore complex is capable of accommodating.

"The HIV-1 capsid is one of the largest things that we now know can go through the nuclear pore complex intact," Weiskopf says. "It raises all kinds of questions — what other things could be going through the pore that we thought was impossible?"

Schwartz said another question is whether all of the 2,000 nuclear pores in human cells are identical or whether there is something that makes certain pores more amenable to allowing the capsid through.

The capsid is also known to be unusually elastic, a property that may be key for passage through the pore. Another interesting question for the field is whether the cone-shaped capsid gains entry into the pore by squeezing through.

Although the team has shown that the capsid can enter the pore, what happens at the other end of the channel is still unknown — whether the capsid fully or partially enters the nucleus or breaks down inside the channel. Weiskopf is working on perturbing parts of the capsid or the spaghetti-like proteins to learn more about which interactions are most important for successful capsid entry.

Although these results have expanded our understanding of the nuclear pore, much remains unknown, both for HIV-1 infection and for the transport process through the nuclear pore complex.  

"The nuclear pore is such an important element of cell biology, we thought it would be interesting to understand it better — and that's how we figured out that the pore is much bigger than we anticipated," Schwartz says. "We will certainly try to see whether we can understand the mechanism of HIV-1 infection, how the capsid is released on the other side of the channel, and what factors are important there — and to what extent you can manipulate it or influence it for therapeutic applications."

This research was carried out, in part, using MIT.nano facilities.

There is vast opportunity for nanoscale innovation to transform the world in positive ways — expressed MIT.nano Director Vladimir Bulović as he posed two questions to attendees at the start of the inaugural Nano Summit: “Where are we heading? And what is the next big thing we can develop?”

“The answer to that puts into perspective our main purpose — and that is to change the world,” Bulović, the Fariborz Maseeh Professor of Emerging Technologies, told an audience of more than 325 in-person and 150 virtual participants gathered for an exploration of nano-related research at MIT and a celebration of MIT.nano’s fifth anniversary.

Over a decade ago, MIT embarked on a massive project for the ultra-small — building an advanced facility to support research at the nanoscale. Construction of MIT.nano in the heart of MIT’s campus, a process compared to assembling a ship in a bottle, began in 2015, and the facility launched in October 2018.

Fast forward five years: MIT.nano now contains nearly 170 tools and instruments serving more than 1,200 trained researchers. These individuals come from over 300 principal investigator labs, representing more than 50 MIT departments, labs, and centers. The facility also serves external users from industry, other academic institutions, and over 130 startup and multinational companies. And in 2022, MIT.nano's home — Building 12 — was named in honor of Lisa T. Su ’90, SM ’91, PhD ’94, chief executive officer and chair of the Board of Directors of AMD.

A cross section of these faculty and researchers joined industry partners and MIT community members to kick off the first Nano Summit, which is expected to become an annual flagship event for MIT.nano and its industry consortium. Held on Oct. 24, the inaugural conference was co-hosted by the MIT Industrial Liaison Program.

Six topical sessions highlighted recent developments in quantum science and engineering, materials, advanced electronics, energy, biology, and immersive data technology. The Nano Summit also featured startup ventures and an art exhibition.

Watch the videos here.

Seeing and manipulating at the nanoscale — and beyond

“We need to develop new ways of building the next generation of materials,” said Frances Ross, the TDK Professor in Materials Science and Engineering (DMSE). “We need to use electron microscopy to help us understand not only what the structure is after it’s built, but how it came to be. I think the next few years in this piece of the nano realm are going to be really amazing.”

Speakers in the session “The Next Materials Revolution,” chaired by MIT.nano co-director for Characterization.nano and associate professor in DMSE James LeBeau, highlighted areas in which cutting-edge microscopy provides insights into the behavior of functional materials at the nanoscale, from anti-ferroelectrics to thin-film photovoltaics and 2D materials. They shared images and videos collected using the instruments in MIT.nano’s characterization suites, which were specifically designed and constructed to minimize mechanical-vibrational and electro-magnetic interference.

Later, in the “Biology and Human Health” session chaired by Boris Magasanik Professor of Biology Thomas Schwartz, biologists echoed the materials scientists, stressing the importance of the ultra-quiet, low-vibration environment in Characterization.nano to obtain high-resolution images of biological structures.

“Why is MIT.nano important for us?” asked Schwartz. “An important element of biology is to understand the structure of biology macromolecules. We want to get to an atomic resolution of these structures. CryoEM (cryo-electron microscopy) is an excellent method for this. In order to enable the resolution revolution, we had to get these instruments to MIT. For that, MIT.nano was fantastic.”

Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences, shared CryoEM images from her lab’s work, followed by biology Associate Professor Joey Davis who spoke about image processing. When asked about the next stage for CryoEM, Davis said he’s most excited about in-situ tomography, noting that there are new instruments being designed that will improve the current labor-intensive process.

To chart the future of energy, chemistry associate professor Yogi Surendranath is also using MIT.nano to see what is happening at the nanoscale in his research to use renewable electricity to change carbon dioxide into fuel.

“MIT.nano has played an immense role, not only in facilitating our ability to make nanostructures, but also to understand nanostructures through advanced imaging capabilities,” said Surendranath. “I see a lot of the future of MIT.nano around the question of how nanostructures evolve and change under the conditions that are relevant to their function. The tools at MIT.nano can help us sort that out.”

Tech transfer and quantum computing

The “Advanced Electronics” session chaired by Jesús del Alamo, the Donner Professor of Science in the Department of Electrical Engineering and Computer Science (EECS), brought together industry partners and MIT faculty for a panel discussion on the future of semiconductors and microelectronics. “Excellence in innovation is not enough, we also need to be excellent in transferring these to the marketplace,” said del Alamo. On this point, panelists spoke about strengthening the industry-university connection, as well as the importance of collaborative research environments and of access to advanced facilities, such as MIT.nano, for these environments to thrive.

The session came on the heels of a startup exhibit in which eleven START.nano companies presented their technologies in health, energy, climate, and virtual reality, among other topics. START.nano, MIT.nano’s hard-tech accelerator, provides participants use of MIT.nano’s facilities at a discounted rate and access to MIT’s startup ecosystem. The program aims to ease hard-tech startups’ transition from the lab to the marketplace, surviving common “valleys of death” as they move from idea to prototype to scaling up.

When asked about the state of quantum computing in the “Quantum Science and Engineering” session, physics professor Aram Harrow related his response to these startup challenges. “There are quite a few valleys to cross — there are the technical valleys, and then also the commercial valleys.” He spoke about scaling superconducting qubits and qubits made of suspended trapped ions, and the need for more scalable architectures, which we have the ingredients for, he said, but putting everything together is quite challenging.

Throughout the session, William Oliver, professor of physics and the Henry Ellis Warren (1894) Professor of Electrical Engineering and Computer Science, asked the panelists how MIT.nano can address challenges in assembly and scalability in quantum science.

“To harness the power of students to innovate, you really need to allow them to get their hands dirty, try new things, try all their crazy ideas, before this goes into a foundry-level process,” responded Kevin O’Brien, associate professor in EECS. “That’s what my group has been working on at MIT.nano, building these superconducting quantum processors using the state-of-the art fabrication techniques in MIT.nano.”

Connecting the digital to the physical

In his reflections on the semiconductor industry, Douglas Carlson, senior vice president for technology at MACOM, stressed connecting the digital world to real-world application. Later, in the “Immersive Data Technology” session, MIT.nano associate director Brian Anthony explained how, at the MIT.nano Immersion Lab, researchers are doing just that.

“We think about and facilitate work that has the human immersed between hardware, data, and experience,” said Anthony, principal research scientist in mechanical engineering. He spoke about using the capabilities of the Immersion Lab to apply immersive technologies to different areas — health, sports, performance, manufacturing, and education, among others. Speakers in this session gave specific examples in hardware, pediatric health, and opera.

Anthony connected this third pillar of MIT.nano to the fab and characterization facilities, highlighting how the Immersion Lab supports work conducted in other parts of the building. The Immersion Lab’s strength, he said, is taking novel work being developed inside MIT.nano and bringing it up to the human scale to think about applications and uses.

Artworks that are scientifically inspired

The Nano Summit closed with a reception at MIT.nano where guests could explore the facility and gaze through the cleanroom windows, where users were actively conducting research. Attendees were encouraged to visit an exhibition on MIT.nano’s first- and second-floor galleries featuring work by students from the MIT Program in Art, Culture, and Technology (ACT) who were invited to utilize MIT.nano’s tool sets and environments as inspiration for art.

In his closing remarks, Bulović reflected on the community of people who keep MIT.nano running and who are using the tools to advance their research. “Today we are celebrating the facility and all the work that has been done over the last five years to bring it to where it is today. It is there to function not just as a space, but as an essential part of MIT’s mission in research, innovation, and education. I hope that all of us here today take away a deep appreciation and admiration for those who are leading the journey into the nano age.”

We often talk about evolution in terms of competition, as the survival of the fittest. But if it is, then where did the widespread (and widely admired) impulse to help others even at great cost to ourselves come from? In this episode, Stephanie Preston, a professor of psychology and head of the Ecological Neuroscience Lab at the University of Michigan, talks about the evolutionary...

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