Thousands of tiny worms will be launched into space today (3 June) to help scientists to understand more about muscle loss and how to prevent it.
Led by scientists from the University of Nottingham and the University of Exeter, with hardware designed by Oxford-based Kayser Space, the research team aims to determine the causes of muscle changes during spaceflight and find ways to mitigate these biological changes.
Spaceflight is an extreme environment that causes many negative changes to the body, with astronauts losing up to 40 percent of their muscle after six months in space.
Based on these changes, spaceflight is regarded as an excellent model to enhance understanding of ageing, inactivity and certain clinical conditions on different body systems.
Studying changes in muscle that occur with spaceflight could lead to more effective therapies and new treatments for age-associate muscle loss and muscular dystrophies.
Previous research revealed that the microscopic worm, C. elegans, and humans experience similar molecular changes in space that affect muscle and metabolism.
This new mission, which follows on from previous research carried out by the same research team in 2018, will see the worms once again launched into space to try to identify the precise molecules that cause these problems.
The mission will also test out new therapies to prevent muscle loss in zero-gravity – including compounds developed at the University of Exeter.
Dr Bethan Philips, Associate Professor of Clinical, Metabolic and Molecular Physiology, in the School of Medicine at the University of Nottingham, is one of the researchers leading this study.
She said: “Since the dawn of the space age, there have been concerns that space travel can be harmful to astronauts.
“We are very excited that this latest mission will enable us to build on the work we have already done to not only further explore what causes muscle loss with spaceflight, but to also look at how to prevent it.
“This work will have implications not only for astronauts but also for many situations on Earth.”
Worms will by loaded with bacterial food into culture bags, and these will be placed into experimental containers.
These containers will be stored at low temperature (about 10◦C) from set-up through to arrival at the International Space Station (ISS).
Once on board the ISS, containers will be placed in a 20◦C incubator for the experimental period of five to six days.
The containers will then be frozen and returned to Earth.
Gene expression and molecule localisation experiments will then be performed at the University of Nottingham.
Tim Etheridge, Associate Professor of Integrative Physiology at the University of Exeter, said: “This experiment will give us new information on the molecules that cause muscle decline in space, and whether targeting these with novel drugs and interventions can help.
“This information can then build the foundations for safely sending humans on long-term missions into deep space.”
Kayser Space, based in Oxfordshire, have developed the hardware for the experiment.
David Zolesi, Kayser Space Managing Director, said: “This launch is the second of a series of three life science payloads developed by Kayser Space to fly to the ISS within three years.
“It is an important achievement that will help Kayser to bolster its position as a leading partner to the UK scientific community for implementing experiments in space.”
The launch is expected to take place on Thursday 3rd June at 18:00 BST. A live stream of the launch can be watched here.
Research helps explain baffling neurological symptoms — and why they’re so unpredictable
New research offers an up-close view of how SARS-CoV-2, the virus that causes COVID-19, can spread to the brain. The study helps explain the alarming array of neurological symptoms reported in some patients with COVID-19, as well as why some patients suffer severe neurological effects while others experience none at all.
The researchers report evidence that SARS-CoV-2 can infect both the nerve cells that power our brains (neurons), and the cells in the brain and spinal cord that support and protect neurons (astrocytes).
“Our findings suggest that astrocytes are a pathway through which COVID-19 causes neurological damage,” said Ricardo Costa, PhD, a postdoctoral fellow at the Louisiana State University (LSU) Health Shreveport and the study’s first author. “This could explain many of the neurologic symptoms we see in COVID-19 patients, which include loss of sense of smell and taste, disorientation, psychosis and stroke.”
Costa will present the research at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. The study is led by Diana Cruz-Topete, assistant professor of molecular and cellular biology at LSU Health Shreveport, and includes collaborators Oscar Gomez-Torres, PhD, and Emma Burgos-Ramos, PhD, from Universidad de Castilla-La Mancha in Spain.
In the respiratory system, SARS-CoV-2 is known to infect a person’s cells by grabbing hold of proteins on the cell surface called angiotensin-converting enzyme-2 (ACE2) receptors. It has been unclear whether brain cells have this receptor.
For the study, Costa and colleagues examined RNA and proteins to determine whether cell cultures of human astrocytes and neurons expressed ACE2. They then exposed the cells to a version of the SARS-CoV-2 virus that had been modified to be safe for researchers to handle. The studies confirmed that both astrocytes and neurons express the ACE2 receptor and that both cell types can become infected with SARS-CoV-2, though astrocytes were less likely to become infected.
Astrocytes are the main gateway to the brain, responsible for shuttling nutrients from the bloodstream to the neurons while keeping harmful particles out. By resisting infection, astrocytes could help keep SARS-CoV-2 out of the brain, but once infected, they could easily pass the virus along to many neurons, according to researchers.
“While astrocytes display a higher resistance to infection, neurons seem to be more susceptible,” said Costa. “This suggests that only few astrocytes getting infected could be sufficient for the infection to quickly spread to neurons and multiply quickly. These observations could explain why while some patients do not have any neurological symptoms, others seem to have severe ones.”
Costa will present this research from 3:15-3:30 p.m. Tuesday, April 27 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.
Worms don’t like the blues. At least not the blue-tinged toxic bacteria that are common in the environmental trash heaps they call home. So how does a bacteria-foraging worm — without eyes, photoreceptors, or the opsin genes that help animals perceive color — avoid the toxic, blue-reflecting bacterium Pseudomonas aeruginosa?
Until recently, Yale’s Michael Nitabach thought worms must recognize distinct chemical chemosensory odors emitted by this bacterium. D. Dipon Ghosh, a former graduate student in Nitabach’s lab, wondered if worms could also have the capacity to somehow sense colors.
“I told him he was being ridiculous,” said Nitabach, professor of cellular and molecular physiology, of genetics and of neuroscience.
Turns out Ghosh was right. In the March 5 issue of the journal Science, Nitabach and Ghosh report how worms manage to detect color in complete absence of a basic visual system.
This discovery expands our current ideas about the possible range of sensitivities that cells and organisms — even those that lack the proteins required for vision — might have to light in their environment.
In a series of experiments, the research team exposed different strains of the worm Caenorhabditis elegans to either the colorful P. aeruginosa bacteria in white light or to colorless E. coli bacteria in light of varying color spectra. They found that while some family members require both a chemical signaling toxic bacteria and a specific color to decide to avoid the bactera, others avoid the bacteria based on color alone. In both cases, the worm’s decision on whether to avoid the bacteria was guided by the color of light in its environment.
The lab also identified two genes in worms that are associated with the ability to gauge color. In mammals, these same genes help regulate the response to stress and can be activated by exposure to ultraviolet light.
“What the worm is doing is something very smart,” Nitabach said. “They are trying to generate a more accurate picture of external reality by employing multiple senses at same time.”
The researchers speculate that this ability helps worm engage in healthy foraging. For example, for worms that have been exposed to toxic bacteria that secrete blue pigments, avoiding the blues might be a really good idea.
Reference: D. Dipon Ghosh, Dongyeop Lee, Xin Jin, H. Robert Horvitz, Michael N. Nitabach, “C. elegans discriminates colors to guide foraging”, Science 05 Mar 2021: Vol. 371, Issue 6533, pp. 1059-1063 DOI: 10.1126/science.abd3010
An international study in which the University of Granada participated—recently published in the journal Scientific Reports—has identified a new fossil record of these mysterious animals in the northeast of Taiwan (China), in marine sediments from the Miocene Age (between 23 and 5.3 million years ago)
These organisms, similar to today’s Bobbit worm (Eunice aphroditois), were approximately 2 m long and 3 cm in diameter and lived in burrows
An international study in which the University of Granada (UGR) participated (recently published in the prestigious journal Scientific Reports) has revealed that the seafloor was inhabited by giant predatory worms during the Miocene Age (23–5.3 million years ago).
The scientists identified a new fossil record (indirect remains of animal activity such as, for instance, dinosaur tracks, fossilised droppings, insect nests, or burrows) linked to these mysterious animals, which are possible predecessors of today’s Bobbit worm (Eunice aphroditois). Based on the reconstruction of giant burrows observed in Miocene-age marine sediments from northeast Taiwan (China), the researchers concluded that these trace fossils may have colonised the seafloor of the Eurasian continent about 20 million years ago.
Olmo Míguez Salas of the UGR’s Department of Stratigraphy and Palaeontology (Ichnology and Palaeoenvironment Research Group) participated in the study, which was conducted as part of a project funded by the Taiwanese Ministry of Science and Technology (MOST, 2018) of which the researcher was a beneficiary.
Míguez Salas and the other researchers reconstructed this new fossil record, which they have named Pennichnus formosae. Itconsists of an L-shaped burrow, approximately 2 m long and 2–3 cm in diameter, indicating the size and shape of the organism— Eunice aphroditois—that made the structure.
Bobbit worms hide in long, narrow burrows in the seafloor and propel themselves upward to grab prey with their strong jaws. The authors suggest that the motion involved in capturing their prey and retreating into their burrow to digest it caused various alterations to the structure of the burrows. These alterations are conserved in the Pennichnus formosae and are indicative of the deformation of the sediment surrounding the upper part of the burrow. Detailed analysis revealed a high concentration of iron in this upper section, which may, the researchers believe, indicate that the worms continuously rebuilt the opening to the burrow by secreting a type of mucus to strengthen the wall, because bacteria that feed on this mucus create environments rich in iron.
Although marine invertebrates have existed since the early Paleozoic, their bodies primarily comprise soft tissue and are therefore rarely preserved. The fossil record discovered in this study is believed to be the earliest known specimen of a subsurface-dwelling ambush predator.
Olmo Míguez Salas notes that this finding “provides a rare view of the behaviour of these creatures under the seafloor and also highlights the value of studying fossil records to understand the behaviour of organisms from the past.”
Featured image: Eunice aphroditois (image courtesy of Ms. Chutinun Mora)
Light-controlled genes could reveal how gut bacteria impact health.
Baylor College of Medicine researcher Meng Wang had already shown that bacteria that make a metabolite called colanic acid (CA) could extend the lifespan of worms in her lab by as much as 50%, but her collaboration with Rice University synthetic biologist Jeffrey Tabor is providing tools to answer the bigger question of how the metabolite imparts longer life.
In a study published in eLife, Wang, Tabor and colleagues showed they could use different colors of light to turn gut bacteria genes on and off while the bacteria were in the intestines of worms. The work was made possible by an optogenetic control system Tabor has been developing for more than a decade.
“Meng’s group discovered that the CA compound could extend lifespan but they couldn’t say for sure whether this was a dietary ingredient that was being digested in the stomach or a metabolite that was being produced by bacteria in the intestines,” said Tabor, an associate professor of bioengineering and of biosciences at Rice. “We were able to restrict production of CA to the gut and show that it had a beneficial effect on cells in the intestines.”
For the experiments, Tabor’s lab engineered strains of E. coli to make CA when exposed to green, but not red, light. To make sure the bacteria worked properly, the team added genes to make different colors of fluorescent proteins that would show up brightly under a microscope. One color was always present, to make it easy to see where the bacteria were inside the worms, and a second color was made only when the bacteria were producing CA.
In collaboration with the Wang lab, Tabor’s lab kept the bacteria under a red light and fed them to worms, a species called Caenorhabditis elegans (C. elegans) that’s commonly used in life sciences. Researchers tracked the bacteria’s progress through the digestive tract and switched on the green light when they made it to the intestines.
In the cells of C. elegans and other higher order life, from humans to yeast, specialized organelles called mitochondria supply most of the energy. Thousands of mitochondria work around the clock in each cell and maintain a dynamic balance between fission and fusion, but they become less efficient over time. As people and other organisms age, the dysfunction of mitochondria leads to functional decline in their cells.
In prior experiments with C. elegans, Wang and colleagues showed that CA can regulate the balance between mitochondrial fission and fusion in both intestinal and muscle cells to promote longevity. The worms typically live about three weeks, but Wang’s lab has shown that CA can extend their lives to 4.5 weeks — 50% longer than usual.
Tabor said this raises a host of questions. For instance, if CA is produced in the gut, do intestinal cells benefit first? Is the beneficial effect of CA related to its level? And most important, do the mitochondrial benefits spread throughout the body from the intestines?
In the eLife study, the researchers found that CA production in the gut directly improved mitochondrial function in intestinal cells in a short time. They did not find evidence of such direct, short-term mitochondrial benefits in the worms’ muscle cells. Thus, the longevity-promoting effect of CA starts from the gut and then spreads into other tissues over time.
“With our technology, we can use light to turn on CA production and watch the effect travel through the worm,” Tabor said.
He said the precision of the optogenetic technology could allow researchers to ask fundamental questions about gut metabolism.
“If you can control the timing and location of metabolite production with precision, you can think about experimental designs that show cause and effect,” he said.
Showing that gut bacteria directly impact health or disease would be a major achievement.
“We know gut bacteria affect many processes in our bodies,” Tabor said. “They’ve been linked to obesity, diabetes, anxiety, cancers, autoimmune diseases, heart disease and kidney disease. There’s been an explosion of studies measuring what bacteria you have when you have this illness or that illness, and it’s showing all kinds of correlations.”
But there is a big difference between showing correlation and causality, Tabor said.
“The goal, the thing you really want, is gut bacteria you can eat that will improve health or treat disease,” he said.
But it’s difficult for researchers to prove that molecules produced by gut bacteria cause disease or health. That’s partly because the gut is difficult to access experimentally, and it’s especially difficult to design experiments that show what is happening in specific locations inside the gut.
“The gut is a hard place to access, especially in large mammals,” Tabor said. “Our intestines are 28 feet long, and they’re very heterogeneous. The pH changes throughout and the bacteria change quite dramatically along the way. So do the tissues and what they’re doing, like the molecules they secrete.
“To answer questions about how gut bacteria influence our health, you need to be able to turn on genes in specific places and at particular times, like when an animal is young or when an animal wakes up in the morning,” he said. “You need that level of control to study pathways on their own turf, where they happen and how they happen.”
Because it uses light to trigger genes, optogenetics offers that level of control, Tabor said.
“To this point, light is really the only signal that has enough precision to turn on bacterial genes in the small versus the large intestine, for example, or during the day but not at night,” he said.
Tabor said he and Wang have discussed many ways they might use optogenetics to study aging.
“She’s found two dozen bacterial genes that can extend lifespan in C. elegans, and we don’t know how most of them work,” Tabor said. “The colanic acid genes are really intriguing, but there are many more that we’d like to turn on with light in the worm to figure out how they work. We can use the exact technique that we published in this paper to explore those new genes as well. And other people who are studying the microbiome can use it too. It’s a powerful tool for investigating how bacteria are benefiting our health.”
Study co-authors include Lucas Hartsough, Matthew Kotlajich, John Tyler Lazar, Elena Musteata and Lauren Gambill of Rice, and Mooncheol Park, Bing Han and Chih-Chun Lin of Baylor. The research was supported by the National Institutes of Health, the National Aeronautics and Space Administration, the John S. Dunn Foundation and the Welch Foundation.
In vitro studies and experiments with mice show that the natural extract was more effective than the only drug available to combat this parasitic disease.
Well-known for its bactericidal and anti-fungal properties, Brazilian red propolis has now been found to act powerfully against the parasite that causes schistosomiasis, reducing the number of eggs and killing the helminths (worms).
In experiments performed at Universidade Guarulhos (UnG) in the state of São Paulo, Brazil, with FAPESP’s support, 400 milligrams per kilogram of body weight was a sufficient dose of red propolis to reduce the parasite load by more than 60% in mice infected with the flatworm Schistosoma mansoni. It was equally effective against the immature and adult stages of the parasite. In vitro tests also showed that red propolis blocked reproduction and oviposition (egg-laying).
“Propolis, especially the red variety, is well-known for its action against bacteria and fungi. It protects the beehive from intruders, and we expected that some of its more than 20 substances would act against parasitic infectious agents. What surprised us was that it disrupted the worm’s integument and killed adult as well as immature worms, which the conventional treatment for schistosomiasis doesn’t do,” said Josué de Moraes, a professor at UnG and last author of the article on the study published in the Journal of Ethnopharmacology.
The results of all the tests suggest red propolis may be more effective to treat schistosomiasis than the only pharmaceutical product available for this purpose. Before red propolis can be prescribed for patients, of course, it must be tested in clinical trials on humans with the disease.
Schistosomiasis is the most common disease caused by helminths and affects some 300 million people worldwide. Despite its high prevalence in tropical and subtropical areas, it has been treated with a single drug for about 40 years.
“Praziquantel is effective but has major limitations,” Moraes said. “In contrast with what we found in the study with red propolis, the drug doesn’t combat infections caused by the immature stage of the parasite. It kills only adult worms, so patients have to wait until the growth cycle reaches the adult stage to start the treatment, by which time the infection has become chronic.”
Another limitation of praziquantel is that some species have become drug-resistant after 40 years with no alternative treatment. Schistosome strains with low susceptibility to the drug have been isolated by researchers.
The research project led by Moraes at UnG’s Center for Research on Neglected Diseases (NPDN) aims at drug repurposing to tackle schistosomiasis. “Because it’s a neglected disease linked to poverty and lack of basic sanitation, this is basically the only way to find novel therapies. Repurposing is cheaper and quicker than developing new drugs from scratch,” Moraes said.
The research group tested 73 nonsteroidal anti-inflammatory drugs sold in Brazil and elsewhere. They found five to be effective against the disease, with mefenamic acid (widely used for menstrual period pain relief) exhibiting the most promising results to date (read more at: agencia.fapesp.br/31372).
In an article published in mid-2020 in Trends in Parasitology, Moraes and a co-author note that the United States’ Food and Drug Administration (FDA) has approved very few drugs for the treatment of parasitic diseases.
“Since the start of the century, the FDA has approved a total of 604 medications, some of which are novel drugs and others repurposed,” Moraes said. “Only nine are antiparasitics, and of these only two are anthelmintics. In my view, helminthiases are the most neglected of neglected diseases.”
Why red propolis?
Moraes explained that the decision to study the effects of red propolis in this project was made because the natural product had been fully characterized in studies by Severino M. Alencar, a researcher at the University of São Paulo’s Luiz de Queiroz College of Agriculture (ESALQ-USP), and Bruno Bueno-Silva at UnG’s Dentistry Department. Both are collaborators with NPDN.
“Brazilian red propolis has attracted attention in recent years owing to its pharmacological potential as well as its anti-microbial and anti-inflammatory action,” he said. “Our study didn’t investigate the mechanism of red propolis in the schistosome but analyzed the action of red propolis extract indirectly using scanning electron microscopy. For example, we set out to see if this natural product, which is made up of several substances, could get through the parasite’s integument. This would increase its power to reach one or more targets and kill the worms, but we didn’t identify any targets.”
Green and brown propolis are likely to have some effect on schistosomiasis, Moraes added, but specific studies will be needed to analyze the other two natural products.
The discovery could also be applicable to other verminoses. “The schistosome is a model for the study of infections in humans and animals caused by other flatworms, or platyhelminths, such as tapeworms of the genus Taenia,” he said. “The discovery, therefore, creates an opportunity for research relating to the treatment of other diseases that affect humans, cats, and dogs, and are also treated with praziquantel.”
Reference: Marcos P. Silva et al, Brazilian red propolis exhibits antiparasitic properties in vitro and reduces worm burden and egg production in an mouse model harboring either early or chronic Schistosoma mansoni infection, Journal of Ethnopharmacology (2020). DOI: 10.1016/j.jep.2020.113387
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
Living at low gravity affects cells at the genetic level, according to a study of worms in space.
Genetic analysis of Caenorhabditis elegans worms on the International Space Station showed “subtle changes” in about 1,000 genes.
Stronger effects were found in some genes, especially among neurons (nervous system cells).
The study, by the University of Exeter and the NASA GeneLab, aids our understanding of why living organisms – including humans – suffer physical decline in space.
“We looked at levels of every gene in the worms’ genome and identified a clear pattern of genetic change,” said Dr Timothy Etheridge, of the University of Exeter.
“These changes might help explain why the body reacts badly to space flight.
“It also gives us some therapy targets in terms of reducing these health effects, which are currently a major barrier to deep-space exploration.”
The study exposed worms to low gravity on the International Space Station, and to high gravity in centrifuges.
The high-gravity tests gave the researchers more data on gravity’s genetic impacts, and allowed them to look for possible treatments using high gravity in space.
“A crucial step towards overcoming any physiological condition is first understanding its underlying molecular mechanism,” said lead author Craig Willis, of the University of Exeter.
“We have identified genes with roles in neuronal function and cellular metabolism that are affected by gravitational changes.
“These worms display molecular signatures and physiological features that closely mirror those observed in humans, so our findings should provide foundations for a better understanding of spaceflight-induced health decline in mammals and, eventually, humans.”
Dr Etheridge added: “This study highlights the ongoing role of scientists from Europe and the UK in space flight life sciences research.”
Research in C. elegans shows how melatonin activates the BK channel in the brain.
Melatonin is used as a dietary supplement to promote sleep and get over jet lag, but nobody really understands how it works in the brain. Now, researchers at UConn Health show that melatonin helps worms sleep, too, and they suspect they’ve identified what it does in us.
Our bodies produce melatonin in darkness. It’s technically a hormone, but you can readily buy melatonin as a supplement in pharmacies, nutrition stores, and other retail shops. It’s widely used by adults and often in children as well.
Melatonin binds to melatonin receptors in the brain to produce its sleep-promoting effects. Think of a receptor as a keyhole, and melatonin as the key. The two keyholes for melatonin are called MT1 and MT2 in human brain cells. But scientists didn’t really know what happens when the keyhole is unlocked. Now UConn Health School of Medicine neuroscientists Zhao-Wen Wang and Bojun Chen and their colleagues have identified that process through their work with C. elegans worms, as reported in PNAS on Sept. 21. When melatonin fits into the MT1 receptor in the worm’s brain, it opens a potassium channel known as the BK channel.
A major function of the BK channel in neurons is to limit the release of neurotransmitters, which are chemical substances used by neurons to talk to each other. In their search for factors related to the BK channel, the Wang and Chen labs found that a melatonin receptor is needed for the BK channel to limit neurotransmitter release. They subsequently found that melatonin promotes sleep in worms by activating the BK channel through the melatonin receptor. Worms that lack either melatonin secretion, the melatonin receptor, or the BK channel spend less time in sleep.
But wait–worms sleep?
Indeed they do, says Chen. There’s actually been quite a lot of research on worm sleep, and researchers found that sleep is similar between worms and mammals like humans and mice.
Wang and Chen next plan to see if the melatonin-MT1-BK relationship holds in mice. The BK channel is involved in all kinds of bodily happenings, from epilepsy to high blood pressure. By learning more about the relationships between the BK channel, sleep, and behavioral changes, the researchers hope both to understand melatonin better and also help people who suffer from other diseases related to the BK channel.
Evgeny Popov (Senior Research Associate, Laboratory of the Stratigraphy Oil and Gas Bearing Reservoirs) partook in researching Canadodus suntoki.
A dental plate was found by Canadian national Stephen Suntok on the Pacific coast of British Columbia. Evgeny Popov, a renowned expert in chimaerids, was asked to assist in classification.
“The new species and genus is most close to the extant members of Chimaeridae – Chimaera and Hydrolagus. They are quite widely present in the oceans and comprise about 82% of the existing Holocephali fish,” explains Popov.
The dental plate shows that the extinct Canadodus was close in appearance to the extant relatives, with length between 83 and 125 centimeters. Its diet most likely consisted of worms, mollusks, and crustaceans. The dental plate never left Canada – it was studied in Russia via high-definition photos, adds Popov.
As the scientists report, the finding was rather lucky, because vertebrate fossils are rarely found on the shores of Juan de Fuca Strait.
The research significantly contributes to the understanding of chimaerid fauna of the late Paleogene in the Pacific Ocean.