The multicellular robots, ranging in size from the width of a human hair to the point of a sharpened pencil, were made to self-assemble and shown to have a remarkable healing effect on other cells. The discovery is a starting point for the researchers’ vision to use patient-derived biobots as new therapeutic tools for regeneration, healing, and treatment of disease.

The work follows from earlier research in the laboratories of Michael Levin, Vannevar Bush Professor of Biology at Tufts University School of Arts & Sciences, and Josh Bongard at the University of Vermont in which they created multicellular biological robots from frog embryo cells called Xenobots, capable of navigating passageways, collecting material, recording information, healing themselves from injury, and even replicating for a few cycles on their own. At the time, researchers did not know if these capabilities were dependent on their being derived from an amphibian embryo, or if biobots could be constructed from cells of other species.

In the current study, published in Advanced Science, Levin, along with PhD student Gizem Gumuskaya discovered that bots can in fact be created from adult human cells without any genetic modification and they are demonstrating some capabilities beyond what was observed with the Xenobots. The discovery starts to answer a broader question that the lab has posed — what are the rules that govern how cells assemble and work together in the body, and can the cells be taken out of their natural context and recombined into different “body plans” to carry out other functions by design?

In this case, researchers gave human cells, after decades of quiet life in the trachea, a chance to reboot and find ways of creating new structures and tasks. “We wanted to probe what cells can do besides create default features in the body,” said Gumuskaya, who earned a degree in architecture before coming into biology. “By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.” The researchers found that not only could the cells create new multicellular shapes, but they could move in different ways over a surface of human neurons grown in a lab dish and encourage new growth to fill in gaps caused by scratching the layer of cells.

Exactly how the Anthrobots encourage growth of neurons is not yet clear, but the researchers confirmed that neurons grew under the area covered by a clustered assembly of Anthrobots, which they called a “superbot.”

“The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body,” said Levin, who also serves as the director of the Allen Discovery Center at Tufts and is an associate faculty member of the Wyss Institute. “It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage,” said Levin. “We’re now looking at how the healing mechanism works, and asking what else these constructs can do.”

The advantages of using human cells include the ability to construct bots from a patient’s own cells to perform therapeutic work without the risk of triggering an immune response or requiring immunosuppressants. They only last a few weeks before breaking down, and so can easily be re-absorbed into the body after their work is done.

In addition, outside of the body, Anthrobots can only survive in very specific laboratory conditions, and there is no risk of exposure or unintended spread outside the lab. Likewise, they do not reproduce, and they have no genetic edits, additions or deletions, so there is no risk of their evolving beyond existing safeguards.

How Are Anthrobots Made?

Each Anthrobot starts out as a single cell, derived from an adult donor. The cells come from the surface of the trachea and are covered with hairlike projections called cilia that wave back and forth. The cilia help the tracheal cells push out tiny particles that find their way into air passages of the lung. We all experience the work of ciliated cells when we take the final step of expelling the particles and excess fluid by coughing or clearing our throats. Earlier studies by others had shown that when the cells are grown in the lab, they spontaneously form tiny multicellular spheres called organoids.

The researchers developed growth conditions that encouraged the cilia to face outward on organoids. Within a few days they started moving around, driven by the cilia acting like oars. They noted different shapes and types of movement — the first. important feature observed of the biorobotics platform. Levin says that if other features could be added to the Anthrobots (for example, contributed by different cells), they could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.

The team, with the help of Simon Garnier at the New Jersey Institute of Technology, characterized the different types of Anthrobots that were produced. They observed that bots fell into a few discrete categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the point of a sharpened pencil), filling an important niche between nanotechnology and larger engineered devices.

Some were spherical and fully covered in cilia, and some were irregular or football shaped with more patchy coverage of cilia, or just covered with cilia on one side. They traveled in straight lines, moved in tight circles, combined those movements, or just sat around and wiggled. The spherical ones fully covered with cilia tended to be wigglers. The Anthrobots with cilia distributed unevenly tended to move forward for longer stretches in straight or curved paths. They usually survived about 45-60 days in laboratory conditions before they naturally biodegraded.

“Anthrobots self-assemble in the lab dish,” said Gumuskaya, who created the Anthrobots. “Unlike Xenobots, they don’t require tweezers or scalpels to give them shape, and we can use adult cells — even cells from elderly patients — instead of embryonic cells. It’s fully scalable — we can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.”

Little Healers

Because Levin and Gumuskaya ultimately plan to make Anthrobots with therapeutic applications, they created a lab test to see how the bots might heal wounds. The model involved growing a two-dimensional layer of human neurons, and simply by scratching the layer with a thin metal rod, they created an open ‘wound’ devoid of cells.

To ensure the gap would be exposed to a dense concentration of Anthrobots, they created “superbots” a cluster that naturally forms when the Anthrobots are confined to a small space. The superbots were made up primarily of circlers and wigglers, so they would not wander too far away from the open wound.

Although it might be expected that genetic modifications of Anthrobot cells would be needed to help the bots encourage neural growth, surprisingly the unmodified Anthrobots triggered substantial regrowth, creating a bridge of neurons as thick as the rest of the healthy cells on the plate. Neurons did not grow in the wound where Anthrobots were absent. At least in the simplified 2D world of the lab dish, the Anthrobot assemblies encouraged efficient healing of live neural tissue.

According to the researchers, further development of the bots could lead to other applications, including clearing plaque buildup in the arteries of atherosclerosis patients, repairing spinal cord or retinal nerve damage, recognizing bacteria or cancer cells, or delivering drugs to targeted tissues. The Anthrobots could in theory assist in healing tissues, while also laying down pro-regenerative drugs.

Making New Blueprints, Restoring Old Ones

Gumuskaya explained that cells have the innate ability to self-assemble into larger structures in certain fundamental ways. “The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move,” Gumuskaya said. “Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functions — different than those found in nature.”

Taking advantage of the inherently flexible rules of cellular assembly helps the scientists construct the bots, but it can also help them understand how natural body plans assemble, how the genome and environment work together to create tissues, organs, and limbs, and how to restore them with regenerative treatments.

During a two-year survey of soft corals in the Florida Keys, Mary Alice Coffroth, professor emerita of geology at the University at Buffalo, along with a small team of UB researchers, identified three species of octocorals that have survived heat waves. While the coral animal itself may be heat tolerant, Coffroth said that her team concluded that the symbiotic algae inside the coral serve as a protector of sorts.

“The resistance and resilience of Caribbean octocorals offers clues for the future of coral reefs,” Coffroth said.

A recent paper outlining their research, “What makes a winner? Symbiont and host dynamics determine Caribbean octocoral resilience to bleaching,” was published on Nov. 22, in Science Advances by the American Association for the Advancement of Science (AAAS).

Coffroth is the lead author on the study she conducted between 2015 and 2017 with graduate student Louis Buccella, undergraduates Katherine Eaton and Alyssa Gooding and technician Harleena Franklin. Howard Lasker, professor emeritus in the departments of Environment and Sustainability and Geology, also contributed to the study.

Algae helps corals survive heat waves

Both hard and soft coral depend on a nutritional symbiosis with single-celled algae living within their tissues. Warmer waters can cause the symbiosis to break down, resulting in a loss of the algal symbionts, which turns the corals white, a phenomenon known as bleaching.

“Bleaching can lead to coral death,” said Coffroth, who has studied coral reefs in the Florida Keys since 1998, including a more recent study in 2020-21. “It’s unclear if the algae leave or are ejected from the coral.

“In this study, we examined possible mechanisms that contribute to the heightened resistance and resilience of three octocoral species in the face of the recurring marine heat waves leading to bleaching events,” Coffroth said, noting that this is the first study that follows both symbiont genetic makeup and density in Caribbean octocorals before, during and after a major heat wave.

By and large, Caribbean octocorals harbor symbionts within the genus Breviolum, she said. And this symbiont is helping to make the octocoral better able to handle the rising heat.

“The Breviolum densities declined during the heatwaves but recovered quickly,” she explained. “Octocoral mortality was low compared to their scleractinian relatives.”

2014 El Niño prompted research

When Coffroth saw bleached corals during the 2014 El Niño and knew that a similar event was predicted for the following summer, she applied for a Rapid Response Research (RAPID) grant from the National Science Foundation. She was awarded $56,305 and with her master’s student, Buccella, conducted the study in the Keys, following the fate of the octocorals and their symbionts for 28 months.

She and other members of the team made trips to the Keys Marine Lab at the Florida Institute of Oceanography to study the octocorals in the spring and fall of 2015 and 2016 and spring and summer of 2017, recording coral coloration and taking samples to study density of the symbionts and their genetic identity.

“We knew it was critical to follow individual colonies across an event with long-term monitoring of both host and symbiont responses,” she said, “and to examine the response at least at the level of symbiont species, if not the genotype, to identify potentially resilient species.”

Climate change moving faster than coral evolution

Although the study began almost a decade ago, Coffroth said the findings are extremely relevant because they mirror what is happening right now, with the continuing warming of ocean waters, increased storms and major bleaching events across the globe.

“There is evidence that corals are withstanding higher temperature now than they did in the 1960s,” she said. “That signals evolution, but the problem is that climate change is moving too fast, faster than evolution.”

In addition to their beautiful aesthetics, coral reefs provide many benefits to the planet and its inhabitants, including barriers to coastal regions that are susceptible to hurricanes and other tropical storms; habitat for large fish such as grouper and snapper; a tourist destination for snorkeling, fishing and diving; and a source for bioactive compounds used in drugs to treat inflammation and certain kinds of cancer.

“If you a see picture of coral reefs when I started diving in the 1970s and compare it with one now, it makes you want to cry,” she said. “The change is just amazing.”

While she noted that this study has some important observations, further study is needed to better understand what is happening to the ecosystem.

“I’m seeing species bleach that have never bleached before but also ones showing more resilience,” she said. “There is a lot of variation within both the animal and symbiont genera. We need to understand the variation.”

The hope is to continue research into coral reef relationships and the durability of the symbiotic algae while also taking steps to halt the damage to the environment by human action, such as overfishing and the burning of fossil fuels.

“We can’t stop global warming,” Coffroth said. “But the hope is that we can slow it down.”

Sudden inheritance of whole suites of extra gene copies can add redundancy to an organism’s regular sets of functions, actually permitting some of those copies to evolve and express in entirely new ways.

In the case of the East Asian pitcher plant, this mutational freedom may have even fine-turned its ability to capture prey and satisfy its appetite for “meat.”

That’s just one of the findings in a new study that sequences the genome of Nepenthes gracilis, a species of carnivorous plant related to Venus flytraps, as well as sundews, beets and spinach.

“Our findings not only provide key insights into the adaptive landscape of the Nepenthes genome, but also broaden our understanding of how polyploidy — having multiple sets of chromosomes — can stimulate the evolution of new functions,” says Victor Albert, PhD, Empire Innovation Professor in the University at Buffalo Department of Biological Sciences, within the College of Arts and Sciences.

Albert is the co-senior author of the study, which was published Thursday (Nov. 23) in Nature Plants, along with Kenji Fukushima, PhD, of the University of Würzburg in Germany. Other contributors from UB include Charlotte Lindqvist, PhD, professor of biological sciences, and PhD students Emily Caroll and Michaela Richter.

Albert’s work was supported in part by the National Science Foundation.

Recessive subgenomes are more free to change function

The idea of “man-eating plants” has long captured our macabre imaginations. Pitcher plants, however, require a much smaller meal.

They capture insects using their highly specialized pitcher-shaped leaves. The bottom of their pitchers are filled with digestive fluids that drown and eventually break down prey. This process releases nutrients, such as nitrogen and phosphate, that allow pitcher plants to thrive in nutrient-poor habitats.

“Plant carnivory is something of a hunt for fertilizer,” Albert says.

In a 1992 study, Albert and colleagues discovered that the Asian, Australian and American pitcher plants possess similar features despite having evolved independently. Later research published in 2017 showed that each of these species co-opted many of the same ancient proteins.

In this new study, Albert and Fukushima’s teams discovered that the specialized pitcher trap of the Asian pitcher plant, or Nepenthes, may have been promoted by polyploidy. Nepenthes’ lineage had already evolved carnivory, so the duplicated genomes may have simply tweaked its mode of capture.

The team discovered that Nepenthes has a decaploid genome in its diploid state, a complex structure almost unprecedented in flowering plants that reflects possession of five whole-genome multiples, or “subgenomes.”

The team found that the fifth subgenome is “dominant,” retaining more gene copies and expressing them at higher levels than the other four older, “recessive” subgenomes. Yet it’s the recessive subgenomes — not the dominant one — that may carry more of the key genes for Nepenthes’ specialized carnivory.

“The dominant subgenome exhibits greater influence of natural selection pressure to maintain gene functions,” Fukushima says. “Whereas the recessive subgenomes, impacted less by functional preservation, have become more free to vary over evolutionary time.”

Some of Nepenthes’ duplicate carnivory genes may have originally evolved for defending against what eventually became their prey. The enzymes that help Nepenthes break down insects’ hard exoskeletons, for example, were repurposed from those that originally shielded plants from being eaten by these animals.

“This lineage of Nepenthes didn’t evolve new genes to become carnivorous — they grabbed collections, or toolkits, of genes that were already there,” Albert says.

One hypothesis suggests that polyploidy has a negligible effect on long-term evolution, as species with multiplicated genomes may undergo extinction at rates higher than those like humans, which have just two sets of chromosomes. Yet the study’s findings add to the evidence that ancient polyploidy events can sometimes underlie evolutionary jumps still visible among plants today.

Evidence found for the evolution of separate male and female plants

Nepenthes is part of the just 6% of flowering plant species that are dioecious, meaning each individual plant produces either male or female flowers. In fact, Nepenthes is the only dioecious carnivorous plant.

Albert and Fukushima’s team also identified a male-specific region of the genome containing three genes potentially responsible for controlling these sex differences. One of these, called LEAFY, is a key gene expressed early in flower development that acts as a master regulator.

“LEAFY seems to have had a duplicate form and moved into the Y chromosome region of Nepenthes, thereafter diverging in its function. This use of LEAFY is unprecedented so far in flowering plants,” Albert says. “The LEAFY gene is such a central regulator across flowering plants that, when artificially added or deleted through genetic engineering, it will change a plant’s flowering time.”

“Although we now have bioinformatic evidence pointing toward LEAFY being one of the key genes involved in the sex determination mechanism of Nepenthes, actually proving this is going to require further studies in living plants,” he adds.

Their work is published as a critical review in the journal Renewable and Sustainable Energy Reviews on October 22, 2023.

More than half of the world’s population presently resides in urban areas, and this number continues to rise. At the same time, urban areas are the most vulnerable to a changing climate and its associated challenges, including heatwaves, floods, storm surges, and other natural hazards.

Cities are responsible for over 70 percent of global greenhouse gas emissions and consume more than two-thirds of the world’s energy. Scientists know that it is necessary to move beyond the “business as usual” approach to achieving sustainable urban development. The importance of urban CAPs in reducing greenhouse gas emissions and adapting to the impacts of climate change is already well documented. Recent research has highlighted the need for urgent urban climate actions to drastically reduce greenhouse gas emissions and develop systems for climate adaptation.

The Hiroshima University scientists noted the pressing need for a more scholarly criticism of the existing CAPs and their suitability in guiding climate adaptation and mitigation efforts. “Here, we propose the UCAP framework to guide the development of suitable CAPs that are comprehensive and consistent with globally accepted standards and benchmarks. Their study further pilot-tested the UCAP framework with climate plans from 257 cities worldwide,” said Prince Dacosta Aboagye, a doctoral student from Ghana at Hiroshima University.

The framework is intended to guide the development of suitable CAPs. In practice, their goal is for the framework to serve as a tool for developing city-specific CAPs that are consistent with acceptable climate action planning standards and benchmarks. In their UCAP framework, the scientists used approaches in relevant existing climate action planning tools. They also included emerging concepts from academic studies and climate planning reports to enhance the comprehensiveness of the framework.

Their proposed UCAP framework includes 43 globally acknowledged criteria across three stages of climate planning. The suitability analysis shows that more than half of the existing urban CAPs have a medium level of suitability, with almost 40 percent having a weak level of suitability. “We discovered that urban CAPs adopted or published recently (since 2018) are more likely to be suitable than those adopted or published earlier (2015 to 2017). Remarkably, urban CAPs from the Global South are more suitable than those from the Global North, probably due to the influx of consultants and experts in supporting CAP development in Global South cities,” said Ayyoob Sharifi, a professor at Hiroshima University.

The authors hope to see more city governments adopting the UCAP framework to develop suitable climate plans to guide urban climate adaptation and mitigation efforts. This will contribute to reducing the climate risk of urban residents and play an integral role in achieving global climate goals. “In the future, we hope to explore the impacts of suitable CAPs on urban climate mitigation and adaptation efforts. We will build the capacity of city governments and policymakers on the use of the framework for developing and evaluating the suitability status of their CAPs. We will also urge corporate and educational institutions to adopt the UCAP framework in their climate planning,” said Aboagye.

The authors are Prince Dacosta Aboagye from the Graduate School of Humanities and Social Sciences at Hiroshima University and Ayyoob Sharifi from the IDEC Institute at Hiroshima University and the School of Architecture and Design, Lebanese American University.

Deep-sea hydrothermal vents are hot springs on the ocean floor. Sea water penetrates into the ocean crust, becomes heated, and rises to the seafloor surface carrying dissolved nutrients. Around these vents, far from any sunlight, vibrant biological communities are found. Here, microbes play the role of primary producers through chemosynthesis — similar to the role that plants play on land through photosynthesis.

Researchers at Hokkaido University, in collaboration with colleagues at Woods Hole Oceanographic Institution, have been working on understanding microbial diversity at deep-sea hydrothermal environments on the East Pacific Rise based on microbe cultivation studies. They isolated a novel campylobacterial strain from a warm-water vent known as ‘Crab Spa’ and named it Hydrogenimonas cancrithermarum, after the site. Their findings were published in the journal International Journal of Systematic and Evolutionary Microbiology.

“Chemolithoautotrophic species of the class Campylobacteria (aka Epsilonproteobacteria) are recognized as an ecologically important bacterial group at hydrothermal vents, contributing to primary production,” explains Assistant Professor Sayaka Mino, first author of the paper and research group leader at the Faculty of Fisheries Sciences, Hokkaido University. “On the other hand, some members of this class, e.g., Helicobacter, Arcobacter, and Campylobacter, are also well known pathogens of humans and animals.”

Hydrogenimonas is known as the thermophilic (adapted to hot temperatures) genus that is most closely related to mesophilic and pathogenic genera in the class Campylobacteria. Yet, only two described species have so far been reported in this genus. The present study revealed that the new strain represents the first mesophilic (adapted to moderate temperatures) and sulfur-oxidizing bacterium in the genus, expanding the physiological and metabolic characteristics of the genus.

“The discovery of a mesophilic Hydrogenimonas species was unexpected. The strain likely provides us with the opportunity to investigate their evolutionary transition from a thermophilic to a mesophilic and from an autotrophic (capable of creating organic compounds) to a heterotrophic (consumes autotrophs to obtain organic compounds) lifestyle,” says Mino.

They further conducted a comprehensive comparative study of the genomes of Campylobacteria, and discovered that the genes responsible for the phosphotransacetylase-acetate kinase (Pta-AckA) pathway tend to be conserved between Hydrogenimonas and the mesophilic species that subsequently diverged from Hydrogenimonas, regardless of their metabolism and pathogenicity.

“The Pta-AkaA pathway has been reported in a pathogenic Campylobacter species to play an important role in colonizing hosts. While we don’t yet understand its specific role in the genus Hydrogenimonas, the acquisition of the genes might represent a key event that enabled their diversification from deep-sea vents to other environments,” says Dr. Stefan Sievert, leader of the research group at the Woods Hole Oceanographic Institution.

“Nowadays, studies of microbial diversity largely rely on cultivation-independent metagenomic sequencing approaches which produce massive amounts of data,” concludes Mino, “Yet, it is vital to remember the significance of cultivation, as shown by the isolation of the new strain that differs markedly from other members of the genus Hydrogenimonas.” The researchers will continue their efforts to discover new culturable species and thus contribute to the understanding of the diversity of Campylobacteria.

A new study by researchers at the John A. Burns School of Medicine (JABSOM) at the University of Hawaiʻi at Mānoa and Kapiʻolani Medical Center for Women & Children examined placentas donated by women who delivered in Hawaiʻi from 2006 to 2021, and found the presence of microplastic particles in the placenta.

Microplastics are visible to the naked eye, and examples can range from the plastic beads once found in exfoliating soaps, to particles from disintegrating plastic bags, to bits of plastic found in microwavable containers which are then inadvertently consumed by humans.

“We were shocked that these little pieces of plastic were getting across the mom’s gut and landing in the placenta,” said Men Jean Lee, an obstetrician and researcher at JABSOM and Kapiʻolani Medical Center. Lee, Rodrigo Weingrill and Johann Urschitz from UH Mānoa’s Institute for Biogenesis Research co-authored the research recently published in Environment International.

The researchers collected and studied 10 placentas in 2006, 2013 and 2021 and found the presence of microplastics grew each year.

• In 2006, 6 of the 10 placentas contained microplastics.
• In 2013, microplastics were found in 9 of the 10 placentas.
• In 2021, researchers found microplastics in all 10 placentas.

“We believe that the plastics may be floating around in food or being inhaled. It’s coming through our digestive fluids or lungs, and the particles are getting absorbed through the gut and traveling through the bloodstream, and then somehow collecting in the placenta during pregnancy,” Lee said. “The big question is, as it’s traveling through the placenta, can it get through the umbilical cord and then to the baby? We don’t know that right now.”

Link to global plastic production

We know that the rise in microplastics found in the placentas of Hawaiʻi mothers corresponds with the skyrocketing levels of global plastic production.

According to the Journal of Hazardous Materials, more than 6,000 megatons of plastic were produced in 2020. Less than 2,000 megatons were produced in 2000.

The big question is, as it’s traveling through the placenta, can it get through the umbilical cord and then to the baby? — Men Jean Lee

Lee believes HHawaiʻi’s remote location creates an added dependency on plastic.

“We’re the world’s most remote population center or island chain. We’re 2,300 miles from California and 4,000 miles from Japan,” Lee said. “For daily conveniences, we commonly use plastic wrap, plastic containers, plastic bags and single use water bottles.”

She suggests Hawaiʻi’s location in the center of the Pacific Ocean, tropical climate, and lack of recycling centers can exacerbate how these plastics are disintegrating or breaking down.

“The incineration of garbage, landfills and marine pollution affect our communities. When trash is being burned, dust particles are released, and can spread into the air we breathe,” Lee said. “In fact, we are concerned about how the debris from the recent Lahaina fires may contain microplastics and other chemical toxins in the remains of the fires. Meanwhile, we already know that sunlight, heat and salt can speed up the breakdown of these everyday plastics. I’ve noticed plastic bags, even shoes, wear out quickly in Hawaiʻi and turn to dust. I never experienced this when I was living back in New York.”

Can microplastics enter the fetus too?

Lee and the JABSOM researchers will continue their research, now focused on seeing if the microplastics can pierce the protection of the placenta and enter the fetus before birth.

“We’re not trying to scare people,” Lee said, but acknowledges there are other questions that still need to be answered. “What are the sources of maternal microplastics? What are the plastics doing in the mother’s body and the placenta? Are they benign, or are they crossing over to the fetal side into the umbilical cord that is connected to the baby? If they are getting to the other side, are they affecting fetal growth and what happens to the baby when he/she grows up?”