FUNGI FUN

Finding a home for the wandering mushrooms —— Phylogenetic and taxonomic updates of Agaricales

Peer-Reviewed Publication

TSINGHUA UNIVERSITY PRESS

 

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THE AGARICALES WAS DIVIDED IN TO 10 SUBORDERS. PHYLLOTOPSIDINEAE AND SARCOMYXINEAE ARE PROPOSED AS NEW SUBORDERS IN THIS STUDY.

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CREDIT: GENG-SHEN WANG, KUNMING INSTITUTE OF BOTANY, CHINESE ACADEMY OF SCIENCES

Many edible, medicinal, and poisonous mushrooms that we are familiar with belong to the order Agaricales, which is a group of fungi with important economic and ecological value. Understanding the phylogenetic relationships of Agaricales can help us to know their evolutionary history and diversity, as well as their interactions with other organisms. Moreover, the phylogenetic framework of Agaricales can provide a basis for conserving biodiversity, such as measuring phylogenetic diversity and assessing the uniqueness and importance of different species.

 

Previous studies divided Agaricales into 8 suborders and 46 families, but the systematic position and phylogenetic relationship of some genera and species were unclear. For example, genera Tricholomopsis and Sarcomyxa have been controversial for a long time.

 

In collaboration with domestic and international colleagues, the research group of fungal diversity and molecular evolution at Kunming Institute of Botany, Chinese Academy of Sciences, conducted genome skimming of fungal specimens from the genera Tricholomopsis, Sarcomyxa, Macrotyphula, Phyllotopsis, and other related groups, and combined them with publicly available genome data of some other species of Agaricales from databases. Using various analytical methods, such as single-copy orthologous gene extraction, gene conflict detection, phylogenetic tree construction, and topology structure testing, they reconstructed the most resolved and robust phylogenetic framework of Agaricales based on the amino acid sequences of 555 single-copy orthologous genes, and clarified the phylogenetic relationships among suborders, as well as the systematic position of Tricholomopsis and Sarcomyxa. They proposed a new classification system of Agaricales with 10 suborders, and made some adjustments to the members of several suborders. They also formally published 2 new suborders (Sarcomyxineae and Phyllotopsidineae), 1 new genus (Conoloma), 2 new sections, and 6 new species, and solved many problems in the classification of Tricholomopsis in China. They also discussed the substrate preference and cap surface scale evolution of this genus.

 

“It has important scientific significance for further understanding the phylogenetic relationships among the major groups of Agaricales”, Geng-Shen Wang said.

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See the article:

Phylogenetic and taxonomic updates of Agaricales, with an emphasis on Tricholomopsis

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About Mycology

Mycology —— An International Journal on Fungal Biology is a renowned international, peer-reviewed, open access journal that publishes all aspects of mycological research, sponsored by the Institute of Microbiology, Chinese Academy of Sciences and the Mycological Society of China. Since its inception in 2010, Mycology received strong support from mycologists around the world. By publishing cutting-edge research and facilitating collaborations, Mycology strives to advance the understanding and knowledge of mycology, while fostering innovative research and scientific discussions in the field.

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JOURNAL

Mycology&#58 An International Journal on Fungal Biology

DOI

10.1080/21501203.2023.2263031 

A novel strategy for extracting white mycelial pulp from fruiting mushroom bodies

Researchers successfully extract mycelial fibers from fruiting bodies of mushrooms without destroying their microsized mycelial structures

Peer-Reviewed Publication

SHINSHU UNIVERSITY

 

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RESEARCHERS FROM SHINSHU UNIVERSITY REPORT AN INNOVATIVE WAY OF OBTAINING BLEACHED WHITE MYCELIUM FIBERS FROM REISHI AND ENOKI MUSHROOMS WHILE PRESERVING THEIR MICROSCALE MYCELIAL STRUCTURES.

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CREDIT: SATOMI TAGAWA FROM SHINSHU UNIVERSITY, JAPAN

Mycelial fibers, the fibrous cells found in fruiting mushroom bodies, have gained momentum as a sustainable material for making leather and packaging owing to their excellent formability. Recently, a team of researchers from Shinshu University, Japan, has found a simple way of obtaining mycelial fibers, called “mycelial pulp,” from fruiting mushroom bodies and bleaching them using sunlight while keeping their mycelial structures intact.

Every year, humans generate millions of tons of waste, and almost 38% of that waste ends up in a landfill. A significant portion of it is made up of plastic or petroleum-based materials that can neither decompose nor degrade with time. This has led scientists to develop materials that are effective yet good for the environment.

One such alternative and renewable resource is mushroom-based materials. The root-like fruiting bodies of mushrooms, also known as mycelial fibers, have shown promising results as the new age, eco-friendly material for a wide range of consumer and industrial applications. The mycelium fibers from the fruiting body contain proteins, chitin, and polysaccharides, which make them ideal for making packaging materials, soundproofing, textiles, and much more. They are not only versatile but also have low environmental impact, are biodegradable, and have a low cost of production. However, conventional chemical or mechanical treatments used to obtain mycelium fibers have notable shortcomings. Many extraction processes tend to give the materials an unwanted color and often destroy their intricate mycelial structures, thereby limiting their nanoscale applications.

Now, a recent ACS Sustainable Chemistry & Engineering paper, made available online on 21 October 2023 and published on 6 November 2023, provides a simple and effective way of obtaining mycelial pulp and fibers from mushrooms without destroying their structure.

“Mushrooms, previously known primarily as a food resource, will now be utilized in everyday household items, allowing people to choose products that are safe, reliable, and environmentally friendly,” says Assistant Professor Satomi Tagawa from the Faculty of Engineering at Shinshu University, who led this study.

Dr. Tagawa and her team members, Dr. Hiroya Nakauchi, recipient of the Research Fellowship for Young Scientists of Japan Society for the Promotion of Science (JSPS) and Dr. Yoshihiko Amano, Professor at the Faculty of Engineering at Shinshu University, present a novel way of extracting the fibers which ensures that the mycelial structures remain intact.

The team treated the fruiting bodies of enoki mushrooms and the inedible reishi mushrooms with sodium hydroxide and hydrogen peroxide. They then bleached (or decolorized) the obtained substances by exposing them to sunlight. The now white material was subjected to ultrasonic treatment to defibrillate the pulp at a mycelial level. This process produced a dispersion containing micrometer-sized mycelium fibers with intact mycelial structures, as verified by Fourier-transform infrared spectroscopy.

The fibers obtained via this process showed excellent deformability and could be used for designing products like 3D porous sponges, 2D films, and 1D yarns.

Apart from obtaining a versatile mushroom-based material, this simple approach makes a valuable addition to the scrap-and-build approach for fabricating mushroom materials, which can complement the existing bottom-up approaches. “This technology has opened possibilities for upcycling unwanted by-products generated by the mushroom industry and making mushroom materials more circular and easier to reuse. We believe that further research on such sustainable materials and methods could create new industries, provide employment opportunities, and revitalize local communities,” remarks Dr. Tagawa, highlighting the scientific and social impact of their findings.

We hope that this research will help reduce waste on our planet and promote the bioeconomy!

 

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About Shinshu University

Shinshu University is a national university founded in 1949 and located nestled under the Japanese Alps in Nagano known for its stunning natural landscapes. Our motto, "Powered by Nature - strengthening our network with society and applying nature to create innovative solutions for a better tomorrow" reflects the mission of fostering promising creative professionals and deepening the collaborative relationship with local communities, which leads to our contribution to regional development by innovation in various fields. We’re working on providing solutions for building a sustainable society through interdisciplinary research fields: material science (carbon, fibre and composites), biomedical science (for intractable diseases and preventive medicine) and mountain science, and aiming to boost research and innovation capability through collaborative projects with distinguished researchers from the world. For more information visit　https://www.shinshu-u.ac.jp/english/ or follow us on X (Twitter) @ShinshuUni for our latest news.

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JOURNAL

ACS Sustainable Chemistry & Engineering

DOI

10.1021/acssuschemeng.3c04795 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Preparation of Mycelium Pulp from Mushroom Fruiting Bodies

ARTICLE TITLE

Phylogenetic and taxonomic updates of Agaricales, with an emphasis on Tricholomopsis

A high-tech research clinic on wheels

NHLBI study assesses health of residents in rural South for heart, lung disease

Peer-Reviewed Publication

NIH/NATIONAL HEART, LUNG AND BLOOD INSTITUTE

Adults in the rural South region, which includes Appalachia and the Mississippi Delta, have some of the highest rates of heart disease, obesity, high blood pressure, and chronic obstructive pulmonary disease (COPD) in the country. Heart failure rates, for example, are 19% higher in the rural South than in urban areas, while COPD rates are twice as high. It takes a toll as rural residents tend to live shorter lives, compared with urban residents.

No one knows exactly why the disease rates are so high, but researchers supported by the NHLBI are determined to find out.

Since 2021, they have been conducting the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study, a long-term research project aimed at uncovering the roots of these disparities. The researchers hope their findings will lead to actions and policies that help improve the health of the estimated 45 million people living in the region, which includes some of the poorest and most remote areas of the country.

In fact, it can take hours to reach health care in some parts of the region, for example.

To address this problem, the RURAL researchers have come up with a unique solution: They’ve built a state-of-the-art mobile exam unit, or MEU, that will bring to the region badly needed health technologies that make it possible for researchers to get the information they need. The MEU is basically a massive tractor-trailer -- about 52 feet long and weighing 53,000 pounds (26.5 US tons) – with the functionality of an urban primary care office. The custom-made unit houses a high-tech medical imaging room, examination room, laboratory, and waiting room.

David C. Goff, M.D., Ph.D., director of the NHLBI’s Division of Cardiovascular Sciences, said there’s great value in a study like this. “We know a lot about the health of urban populations, but there is a critical gap in research data regarding the health of people in the rural South that needs to be addressed,” he said. “In particular, we’d like to help reduce the region’s high burden of heart and lung diseases, the number one and number six leading causes of death in this country. The RURAL study is an important step toward that goal.”

“This is one of the first epidemiological cohort studies of its kind conducted in the rural South,” said Vasan Ramachandran, M.D., a co-leader of the RURAL Cohort Study and a professor and dean of the School of Public Health at the University of Texas Health Science Center at San Antonio. 

According to Ramachandran, the region’s health decline first became noticeable in the 1980s, and it has steadily worsened. Researchers think they know at least some of what’s contributing to the decline: vast food insecurity, poor access to healthcare, excess weight, and high rates of smoking. But they have had difficulty studying the area in detail – and broadly – due in part to its remoteness and lack of research infrastructure. The vehicle is scheduled to travel through 10 rural counties in Alabama, Kentucky, Louisiana, and Mississippi to conduct a variety of health exams on adult residents ages 25 to 64 who volunteer for the study. Already it’s been to four counties (two in Alabama and two in Mississippi), and about 2,100 participants, roughly half the study’s goal of 4,600 enrollees, have been tested.

Researchers have been looking at routine measures like blood pressure, cholesterol, and blood sugar levels, as well as images of the participants’ heart and lungs. They also have been administering surveys focused on the social determinants of health – the conditions in which people grow up, live, work, and play. Those include questions about education levels, income, neighborhoods, social stresses, and lifestyle, all of which give researchers insights they would never get from health exams alone. 

“So far, we’re seeing striking health challenges, including heart disease at a younger age, as well as high rates of obesity,” said Ramachandran, a former principal investigator for the NHLBI’s Framingham Heart Study, which has followed over 14,000 people since 1948. “Diseases that we saw in participants of the Framingham Heart Study at age 75 are occurring in these rural populations at age 50.” 

While it’s too early to publish comprehensive results from the study, some initial results might be published in early 2024, he said. Data collected by the researchers will be shared with the participants, who will be encouraged to share the information with their healthcare providers. If they do not have a provider, the researchers will refer them to local healthcare professionals. Some health data also will be shared with County officials to help them design improved healthcare policies and programs for the region.

“One of the keys to the success of our project is building up community trust, and we’re doing that by working closely with local community leaders,” Ramachandran said. “The community has welcomed us, and we hope this study will serve as a call to action to improve rural health in the South.”

The study, which is funded through 2025, involves a collaboration with over 50 investigators at 15 institutions nationwide. Researchers hope it will be renewed so they can re-examine the participants during a second visit and see how the diseases have progressed or whether improvements have occurred.

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JOURNAL

Hypertension

Time change for biological aging clocks: How immune cells shape our body's true age

New research reveals the secret to slowing down the aging process is intricately tied to a balance in your immune system.

Peer-Reviewed Publication

DARTMOUTH HEALTH

LEBANON, NH—When asked, “How old are you?” Most people measure by how many birthdays they’ve had. But scientists have developed epigenetic clocks to measure how 'old' your body really is. At the forefront of aging research, these clocks go beyond our calendar age to try and reveal our biological age—a true marker of how healthy we are. However, scientists don't fully understand how they work. As a recent NYT article pointed out, it's a bit like having a sophisticated gadget without a manual. Our bodies' internal workings, especially our immune system, play a huge role, but the details are still unclear.

New research by Dartmouth Cancer Center scientists has taken the first step to change that. The team, led by Ze Zhang, PhD, Lucas Salas, MD, MPH, PhD, and Brock Christensen, PhD, is diving deep into the immune system to learn how different immune cells affect epigenetic clocks, to make them more accurate and reliable.

In their study, “Deciphering the role of immune cell composition in epigenetic age acceleration: Insights from cell-type deconvolution applied to human blood epigenetic clocks,” newly published in Aging Cell, the team determined how our body's biological age is related to our immune system. Using novel tools they recently developed for immune profiling, they were able to more closely examine how immune cell profiles relate with biological age estimates from epigenetic clocks. In particular, the balance between naïve and memory immune cells seems to accelerate or slow down biological aging. Key innovations of the study include:

• Enabling the calculation of Intrinsic Epigenetic Age Acceleration (IEAA) with unprecedented immune cell granularity, allowing for a much more detailed understanding of the aging process at a cellular level.
• Offering a more direct comparison between immune cells and aging than the traditional Extrinsic Epigenetic Age Acceleration (EEAA) method, which only considers a limited range of immune cells.
• Adding a new layer of understanding to the biological interpretation of epigenetic clocks, by mapping out how various immune cell subsets contribute to epigenetic aging and providing insights that previous research has missed.

“Our findings open new doors to a much more detailed understanding of the relationships between the immune system and biological age at a cellular level, and the internal and external factors that influence how quickly we age,” says Zhang.

The implications of these findings are far-reaching, offering new insights into the aging process and potential pathways for health interventions. Future studies will focus on incorporating groundbreaking findings that link immune cell composition to epigenetic aging into calculating biological age using epigenetic clocks—a significant shift in how we evaluate biological age that will ensure a more comprehensive and accurate assessment.

Upcoming research will delve directly into different immune cells' roles in various disease settings, particularly in different types of cancer. By unraveling the complex roles of immune cells influenced by epigenetic aging, the team’s research could lead to more targeted and effective cancer treatments, a deeper understanding of how cancer develops, and new approaches for precision cancer prevention.

“This exciting trajectory can transform our understanding of disease and aging and open new possibilities in precision prevention, precision medicine, and targeted treatments,” says Zhang. “With these steps, we move closer to a future where predicting and preventing diseases like cancer becomes more precise and effective, guided by the deepened knowledge of biological age and the immune system.”

 

Ze Zhang, PhD, is the lead author of the paper. His research interests include molecular epidemiology, specifically epigenetics in cancer, developmental biology, immunology, and cell heterogeneity.

Lucas Salas, MD, MPH, PhD, is a member of of Dartmouth Cancer Center’s Cancer Population Sciences Research Program, and Assistant Professor of Epidemiology at Dartmouth’s Geisel School of Medicine. His research interests include investigation into how cell heterogeneity impacts human health and disease, with an emphasis on genetic, environmental and lifestyle factors. @lsalas_epigenet

Brock C. Christensen, PhD, Co-Leads the Cancer Population Sciences Research Program at Dartmouth Cancer Center, and is a Professor of Epidemiology, Professor of Community and Family Medicine, and Professor of Molecular and Systems Biology at Dartmouth’s Geisel School of Medicine. His research interests include understanding relationships between epigenetic states and exposures in the context of disease susceptibility, occurrence, and progression. @Brockclarke

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About Dartmouth Cancer Center: Dartmouth Cancer Center combines the advanced cancer research in partnership with Dartmouth and the Geisel School of Medicine, with award-winning, personalized, and compassionate patient-centered cancer care based at the Norris Cotton Cancer Care Pavilion at Dartmouth Hitchcock Medical Center. With 14 locations around New Hampshire and Vermont, Dartmouth Cancer Center is one of only 56 National Cancer Institute-designated Comprehensive Cancer Centers. Each year the Dartmouth Cancer Center schedules 74,000 appointments seeing more than 4,500 newly diagnosed patients and currently offers patients more than 240 active clinical trials. Celebrating its 50th anniversary in 2022, Dartmouth Cancer Center remains committed to excellence, outreach and education. We strive to prevent and cure cancer, enhance survivorship and to promote cancer health equity through pioneering interdisciplinary research and collaborations. Learn more at http://cancer.dartmouth.edu.

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JOURNAL

Aging Cell

DOI

10.1111/acel.14071 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Deciphering the role of immune cell composition in epigenetic age acceleration: Insights from cell-type deconvolution applied to human blood epigenetic clocks

Surprisingly simple model explains how brain cells organize and connect

ANARCHY IS IN YOUR HEAD

Scientists from UChicago, Harvard, and Yale propose a self-organizing model of connectivity that applies across a wide range of organisms and potentially other types of networks as well.

@ IS SELF ORGANIZATION

UNIVERSITY OF CHICAGO

A new study by physicists and neuroscientists from the University of Chicago, Harvard and Yale describes how connectivity among neurons comes about through general principles of networking and self-organization, rather than the biological features of an individual organism.

The research, published on January 17, 2024 in Nature Physics, accurately describes neuronal connectivity in a variety of model organisms and could apply to non-biological networks like social interactions as well.

“When you’re building simple models to explain biological data, you expect to get a good rough cut that fits some but not all scenarios,” said Stephanie Palmer, PhD, Associate Professor of Physics and Organismal Biology and Anatomy at UChicago and senior author of the paper. “You don’t expect it to work as well when you dig into the minutiae, but when we did that here, it ended up explaining things in a way that was really satisfying.”

Understanding how neurons connect

Neurons form an intricate web of connections between synapses to communicate and interact with each other. While the vast number of connections may seem random, networks of brain cells tend to be dominated by a small number of connections that are much stronger than most.

This “heavy-tailed” distribution of connections (so-called because of the way it looks when plotted on a graph) forms the backbone of circuitry that allows organisms to think, learn, communicate and move. Despite the importance of these strong connections, scientists were unsure if this heavy-tailed pattern arises because of biological processes specific to different organisms, or due to basic principles of network organization.

To answer these questions, Palmer and Christopher Lynn, PhD, Assistant Professor of Physics at Yale University, and Caroline Holmes, PhD, a postdoctoral researcher at Harvard University, analyzed connectomes, or maps of brain cell connections. The connectome data came from several different classic lab animals, including fruit flies, roundworms, marine worms and the mouse retina.

To understand how neurons form connections to one another, they developed a model based on Hebbian dynamics, a term coined by Canadian psychologist Donald Hebb in 1949 that essentially says, “neurons that fire together, wire together.” This means the more two neurons activate together, the stronger their connection becomes.

Across the board, the researchers found these Hebbian dynamics produce “heavy-tailed” connection strengths just like they saw in the different organisms. The results indicate that this kind of organization arises from general principles of networking, rather than something specific to the biology of fruit flies, mice, or worms.

The model also provided an unexpected explanation for another networking phenomenon called clustering, which describes the tendency of cells to link with other cells via connections they share. A good example of clustering occurs in social situations. If one person introduces a friend to a third person, those two people are more likely to become friends with them than if they met separately.

"These are mechanisms that everybody agrees are fundamentally going to happen in neuroscience,” Holmes said. “But we see here that if you treat the data carefully and quantitatively, it can give rise to all of these different effects in clustering and distributions, and then you see those things across all of these different organisms.”

Accounting for randomness

As Palmer pointed out, though, biology doesn’t always fit a neat and tidy explanation, and there is still plenty of randomness and noise involved in brain circuits. Neurons sometimes disconnect and rewire with each other — weak connections are pruned, and stronger connections can be formed elsewhere. This randomness provides a check on the kind of Hebbian organization the researchers found in this data, without which strong connections would grow to dominate the network.

The researchers tweaked their model to account for randomness, which improved its accuracy.

“Without that noise aspect, the model would fail,” Lynn said. “It wouldn’t produce anything that worked, which was surprising to us. It turns out you actually need to balance the Hebbian snowball effect with the randomness to get everything to look like real brains.”

Since these rules arise from general networking principles, the team hopes they can extend this work beyond the brain.

“That’s another cool aspect of this work: the way the science got done,” Palmer said. “The folks on this team have a huge diversity of knowledge, from theoretical physics and big data analysis to biochemical and evolutionary networks. We were focused on the brain here, but now we can talk about other types of networks in future work.”

The study, “Heavy–tailed neuronal connectivity arises from Hebbian self–organization,” was supported by the National Science Foundation, through the Center for the Physics of Biological Function (PHY–1734030) and a Graduate Research Fellowship (C.M.H.); by the James S. McDonnell Foundation through a Postdoctoral Fellowship Award (C.W.L.); and by the National Institutes of Health BRAIN initiative (R01EB026943).

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JOURNAL

Nature Physics

DOI

10.1038/s41567-023-02332-9 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Heavy–tailed neuronal connectivity arises from Hebbian self–organization

ARTICLE PUBLICATION DATE

17-Jan-2024

Novel tissue-derived brain organoids could revolutionize brain research

Peer-Reviewed Publication

PRINCESS MÁXIMA CENTER FOR PEDIATRIC ONCOLOGY

 

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AN IMAGE OF A WHOLE HUMAN FETAL BRAIN ORGANOID. STEM CELLS ARE MARKED BY SOX2 (GREY) AND NEURONAL CELLS (TUJ1) ARE COLOR CODED FROM PINK TO YELLOW BASED ON DEPTH.

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CREDIT: PRINCESS MÁXIMA CENTER, HUBRECHT INSTITUTE/B ARTEGIANI, D HENDRIKS, H CLEVERS

Press release – Princess Máxima Center for pediatric oncology

EMBARGO: 8 JANUARY 2024 AT 11:00 AM ET (US)

 

Scientists have developed 3D mini-organs from human fetal brain tissue that self-organize in vitro. These lab-grown organoids open up a brand-new way of studying how the brain develops. They also offer a valuable means to study the development and treatment of diseases related to brain development, including brain tumors.

Scientists use different ways to model the biology of healthy tissue and disease in the lab. These include cell lines, laboratory animals and, since a few years, 3D mini-organs. These so-called organoids have characteristics and a level of complexity that allows scientists to closely model the functions of an organ in the lab. Organoids can be formed directly from cells of a tissue. Scientists can also ‘guide’ stem cells – found in embryos or in some adult tissues – to develop into the organ they aim to study.

Until now, brain organoids were grown in the lab by coaxing embryonic or pluripotent stem cells to grow into structures representing different areas of the brain. Using a specific cocktail of molecules, they would try to mimic the natural development of the brain – with the ‘recipe’ for each cocktail taking a lot of research to develop.

Now, scientists at the Princess Máxima Center for pediatric oncology and the Hubrecht Institute, both based in Utrecht, the Netherlands, developed brain organoids directly from human fetal brain tissue. The study was published in the prestigious journal Cell today (Monday), and was part-funded by the Dutch Research Council.

The researchers, led by Dr. Delilah Hendriks, Prof. Dr. Hans Clevers and Dr. Benedetta Artegiani, were surprised to find that using small pieces of fetal brain tissue rather than individual cells was vital in growing mini-brains. To grow other mini-organs such as gut, scientists normally break down the original tissue to single cells. Instead working with small pieces of fetal brain tissue, the team found that these pieces could self-organize into organoids.

The brain organoids were roughly the size of a grain of rice. The tissue’s 3D make-up was complex, and it contained a number of different types of brain cells. Importantly, the brain organoids contained many so-called outer radial glia – a cell type found in humans and our evolutionary ancestors. This underlines the organoids’ close similarity to – and use in studying – the human brain.

The whole pieces of brain tissue also produced proteins that make up extracellular matrix – a kind of ‘scaffolding’ around cells. The team believes these proteins could be the reason why the pieces of brain tissue were able to self-organize into 3D brain structures. The presence of extracellular matrix in the organoids will allow further study of the environment of brain cells, and what happens when this goes wrong.

The researchers found that the tissue-derived organoids kept various characteristics of the specific region of the brain from which they were derived. They responded to signaling molecules known to play an important role in brain development. This finding suggests that the tissue-derived organoids could play an important role in untangling the complex network of molecules involved in directing the development of the brain.

Given the ability of the tissue-derived organoids to quickly expand, the team next investigated their potential in modeling brain cancer. The researchers used gene-editing technique CRISPR-Cas9 to introduce faults in the well-known cancer gene TP53 in a small number of cells in the organoids. After three months, the cells with defective TP53 had completely overtaken the healthy cells in the organoid – meaning they had acquired a growth advantage, a typical feature of cancer cells.

They then used CRISPR-Cas9 to switch off three genes linked to the brain tumor, glioblastoma: TP53, PTEN and NF1. The researchers also used these mutant organoids to look at their response to existing cancer drugs. These experiments showed the organoids’ potential for cancer drug research to link certain drugs to specific gene mutations.

The tissue-derived organoids continued to grow in a dish for more than six months. Importantly, the scientists could multiply them, allowing them to grow many similar organoids from one tissue sample. The mini-tumors with the glioblastoma gene changes – were also capable of multiplying, keeping the same mix of mutations. This feature means scientists can carry out repeat experiments with the tissue-derived organoids, increasing the reliability of their findings.

Next, the researchers aim to further explore the potential of their new tissue-derived brain organoids. They also plan to continue their work with bioethicists – who were already involved in shaping this research – to guide the future development and applications of the new brain organoids.

Dr. Benedetta Artegiani, research group leader at the Princess Máxima Center for pediatric oncology who co-led the research, says:

‘Brain organoids from fetal tissue are an invaluable new tool to study human brain development. We can now more easily study how the developing brain expands, and look at the role of different cell types and their environment.

‘Our new, tissue-derived brain model allows us to gain a better understanding of how the developing brain regulates the identity of cells. It could also help understand how mistakes in that process can lead to neurodevelopmental diseases such as microcephaly, as well as other diseases that can stem from derailed development, including childhood brain cancer.’

Dr. Delilah Hendriks, affiliated group leader at the Princess Máxima Center for pediatric oncology, postdoctoral researcher at the Hubrecht Institute and Oncode Investigator, who co-led the research, says:

‘These new fetal tissue-derived organoids can offer novel insights into what shapes the different regions of the brain, and what creates cellular diversity. Our organoids are an important addition to the brain organoid field, that can complement the existing organoids made from pluripotent stem cells. We hope to learn from both models to decode the complexity of the human brain.

‘Being able to keep growing and using the brain organoids from fetal tissue also means that we can learn as much as possible from such precious material. We’re excited to explore the use of these novel tissue organoids for new discoveries about the human brain.’

Prof. dr. Hans Clevers, pioneer in organoid research and former research group leader at the Hubrecht Institute and the Princess Máxima Center for pediatric oncology and Oncode Investigator, co-led the research. He says:

‘With our study, we’re making an important contribution to the organoid and brain research fields. Since we developed the first human gut organoids in 2011, it’s been great to see that the technology has really taken off. Organoids have since been developed for almost all tissues in the human body, both healthy and diseased – including an increasing number of childhood tumors.

‘Until now, we were able to derive organoids from most human organs, but not from the brain – it’s really exciting that we’ve now been able to jump that hurdle as well.’

The study was performed in collaboration with Leiden University Medical Center, Utrecht University, Maastricht University, Erasmus University Rotterdam, and National University of Singapore.

- ENDS -

Notes to editors

The human fetal tissue was derived from healthy abortion material, between gestational weeks 12-15, from fully anonymous donors. The anonymous women donated the tissue voluntarily and upon informed consent. They were informed that the material would be used for research purposes only, and that the research included the understanding of how organs normally develop, including the possibility to grow cells derived from the donated material.

About the Princess Máxima Center for pediatric oncology

When a child is seriously ill from cancer, only one thing matters: a cure.

Every year, 600 children in the Netherlands are diagnosed with cancer. Sadly, one in four of these children dies. That is why in the Princess Máxima Center for pediatric oncology, we work together with passion and without limits every day to improve the survival rate and quality of life of children with cancer. Now, and in the long term. Because children have their whole lives ahead of them.

The Princess Máxima Center is no ordinary hospital, but a research hospital. All children with cancer in the Netherlands are treated here, and it’s where all research into childhood cancer in the country takes place. This makes the Princess Máxima Center the largest pediatric cancer center in Europe. More than 900 healthcare professionals and 450 scientists work closely with Dutch and international hospitals to find better treatments and new perspectives for a cure.

In this way, we offer children today the best possible care, and we take important steps to improve survival for children who cannot not yet be cured.

A zoom-in image of a part of a human fetal brain organoid. Stem cells are marked by SOX2 (cyan) and neuronal cells (TUJ1) are color coded from pink to yellow based on depth.

Four zoom-in images of parts of different human fetal brain organoids. Different neural markers are stained, depicting their cellular heterogeneity and architecture.

CREDIT

Princess Máxima Center, Hubrecht Institute/B Artegiani, D Hendriks, H Clevers

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JOURNAL

Cell

DOI

10.1016/j.cell.2023.12.012 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Human embryos

ARTICLE TITLE

Human fetal brain self-organizes into long-term expanding organoids

ARTICLE PUBLICATION DATE

8-Jan-2024

Fastest swimming insect could inspire uncrewed boat designs

Peer-Reviewed Publication

CORNELL UNIVERSITY

ITHACA, N.Y. – Whirligig beetles, the world’s fastest-swimming insect, achieve surprising speeds by employing a strategy shared by speedy marine mammals and waterfowl, according to a new Cornell University study that rewrites previous explanations of the physics involved.

The centimeter-long beetles can reach a peak acceleration of 100 meters per second and a top velocity of 100 body lengths per second (or one meter per second).

Not only do the results explain the whirligig’s Olympian speeds, but they also offer valuable insights for bio-inspired designers of near-surface water robots and uncrewed boats.

Until now, researchers have believed that whirligigs attain their impressive speeds using a propulsion system called drag-based thrust. This type of thrust requires the insect’s legs to move faster than the swimming speed, in order for the legs to generate any thrust. For the whirligig beetle to achieve such fast swimming speeds, its legs would need to push against the water at unrealistic speeds.

“It could have well been questioned,” said Chris Roh, assistant professor of biological and environmental engineering. “The fastest swimmer and drag-based thrust don’t usually go together in the same sentence.”

In fact, fast-swimming marine mammals and waterfowls tend to forgo drag-based thrust in favor of lift-based thrust, another propulsion system. The finding was described in a study published Jan. 8 in the journal Current Biology.

Using two high-speed cameras synchronized at different angles, the researchers were able to film a whirligig and observe a lift-based thrust mechanism at play. Lift-based thrust works like a propeller, where the thrusting motion is perpendicular to the water surface, eliminating drag and allowing for more efficient momentum capable of greater speed.

Lift-based thrust has previously been identified in large-scale organisms, such as whales, dolphins and sea lions. “In this work, we extended the length-scale down to one centimeter, which means that whirligig beetles are by far the smallest organism to use lift-based thrust for swimming,” said Yukun Sun, a doctoral student in Roh’s lab and the paper’s first author.

“We’re hoping that this speaks to bio-inspired robotics and other engineering communities to first identify the right physics and then try to preserve that physics in creating the robotics,” Roh said.

The U.S. Navy has been developing uncrewed boats, as traditional ship design is constrained by the need to make boats hospitable to a crew. By eliminating a crew, boats can be much smaller and more flexible. Roh believes that the small size, ship-like shape and lift-generating propulsion mechanism of whirligigs translate well to inform robotic ship designs.

The study was funded by the National Science Foundation.

For additional information, see this Cornell Chronicle story.

Media note: Video of the whirligig beetle can be viewed and downloaded here: https://cornell.box.com/v/whirligigbeetles 

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2023.11.008 

ARTICLE TITLE

Whirligig beetle uses lift-based thrust for fastest insect swimming

ARTICLE PUBLICATION DATE

8-Jan-2024