Tag Archives: Bioinformatics

Experts find remnants of ancient RNA viruses embedded inside reef-building corals

2 June, 2023 Admin Leave a comment

Reviewed by Danielle Ellis, B.Sc.Jun 2 2023

An international team of marine biologists has discovered the remnants of ancient RNA viruses embedded in the DNA of symbiotic organisms living inside reef-building corals.

The RNA fragments are from viruses that infected the symbionts as long ago as 160 million years. The discovery is described in an open-access study published this week in the Nature journal Communications Biology, and it could help scientists understand how corals and their partners fight off viral infections today. But it was a surprising find because most RNA viruses are not known for embedding themselves in the DNA of organisms they infect.

The research showed that endogenous viral elements, or EVEs, appear widely in the genomes of coral symbionts. Known as dinoflagellates, the single-celled algae live inside corals and provide them with their dramatic colors. The EVE discovery underscores recent observations that viruses other than retroviruses can integrate fragments of their genetic code into their hosts’ genomes.

So why did it get in there? It could just be an accident, but people are starting to find that these ‘accidents’ are more frequent than scientists had previously believed, and they’ve been found across all kinds of hosts, from bats to ants to plants to algae.”

Adrienne Correa, Study Co-Author, Rice University

That an RNA virus appears at all in coral symbionts was also a surprise.

“This is what made this project so interesting to me,” said study lead author Alex Veglia, a graduate student in Correa’s research group. “There’s really no reason, based on what we know, for this virus to be in the symbionts’ genome.”

The study was supported by the Tara Ocean Foundation and the National Science Foundation and led by Correa, Veglia and two scientists from Oregon State University, postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. The research provides clues that can help scientists better understand the ecological and economic impact of viruses on reef health.

The researchers did not find EVEs from RNA viruses in samples of filtered seawater or in the genomes of dinoflagellate-free stony corals, hydrocorals or jellyfish. But EVEs were pervasive in coral symbionts that were collected from dozens of coral reef sites, meaning the pathogenic viruses were -; and probably remain -; picky about their target hosts.

“There’s a huge diversity of viruses on the planet,” said Correa, an assistant professor of biosciences. “Some we know a lot about, but most viruses haven’t been characterized. We might be able to detect them, but we don’t know who serves as their hosts.”

She said viruses, including retroviruses, have many ways to replicate by infecting hosts. “One reason our study is cool is because this RNA virus is not a retrovirus,” Correa said. “Given that, you wouldn’t expect it to integrate into host DNA.

“For quite a few years, we’ve seen a ton of viruses in coral colonies, but it’s been hard to tell for sure what they were infecting,” Correa said. “So this is likely the best, most concrete information we have for the actual host of a coral colony-associated virus. Now we can start asking why the symbiont keeps that DNA, or part of the genome. Why wasn’t it lost a long time ago?”

The discovery that the EVEs have been conserved for millions of years suggests they may somehow be beneficial to the coral symbionts and that there is some kind of mechanism that drives the genomic integration of the EVEs.

“There are a lot of avenues we can pursue next, like whether these elements are being used for antiviral mechanisms within dinoflagellates, and how they are likely to affect reef health, especially as oceans warm,” Veglia said.

“If we’re dealing with an increase in the temperature of seawater, is it more likely that Symbiodiniaceae species will contain this endogenous viral element? Does having EVEs in their genomes improve their odds of fighting off infections from contemporary RNA viruses?” he said.

“In another paper, we showed there was an increase in RNA viral infections when corals underwent thermal stress. So there are a lot of moving parts. And this is another good piece of that puzzle.”

Correa said, “We can’t assume that this virus has a negative effect. But at the same time, it does look like it’s becoming more productive under these temperature stress conditions.”

Thurber is the Emile F. Pernot Distinguished Professor in Oregon State’s Department of Microbiology.

Source:

Rice University

Journal reference:

Veglia, A. J., et al. (2023). Endogenous viral elements reveal associations between a non-retroviral RNA virus and symbiotic dinoflagellate genomes. Communications Biology. doi.org/10.1038/s42003-023-04917-9.

Microbiology

UNIGE researchers identify how the influenza A virus manages to penetrate host cells

31 May, 2023 Admin Leave a comment

Reviewed by Danielle Ellis, B.Sc.May 31 2023

Influenza epidemics, caused by influenza A or B viruses, result in acute respiratory infection. They kill half a million people worldwide every year. These viruses can also wreak havoc on animals, as in the case of avian flu. A team from the University of Geneva (UNIGE) has identified how the influenza A virus manages to penetrate cells to infect them. By attaching itself to a receptor on the cell surface, it hijacks the iron transport mechanism to start its infection cycle. By blocking the receptor involved, the researchers were also able to significantly reduce its ability to invade cells. These results, published in the journal PNAS, highlight a vulnerability that could be exploited to combat the virus.

Influenza viruses represent a major risk to human and animal health. Their potential for mutation makes them particularly elusive.

‘We already knew that the influenza A virus binds to sugar structures on the cell surface, then rolls along the cell surface until it finds a suitable entry point into the host cell. However, we did not know which proteins on the host cell surface marked this entry point, and how they favored the entry of the virus.”

Mirco Schmolke, Associate Professor, Department of Microbiology and Molecular Medicine and in the Geneva Centre for Inflammation Research (GCIR) at the UNIGE Faculty of Medicine

A receptor as a key to infection

The scientists first identified cell surface proteins present in the vicinity of the viral haemagglutinin, the protein used by the influenza A virus to enter the cell. One of these proteins stood out: transferrin receptor 1. This acts as a revolving door transporting iron molecules into the cell, which are essential for many physiological functions.

”The influenza virus takes advantage of the continuous recycling of the transferrin receptor 1 to enter the cell and infect it,” explains Béryl Mazel-Sanchez, a former post-doctoral researcher in Mirco Schmolke’s laboratory and first author of this work. ”To confirm our discovery, we genetically engineered human lung cells to remove the transferrin receptor 1, or on the contrary to overexpress it. By deleting it in cells normally susceptible to infection, we prevented influenza A from entering. Conversely, by overexpressing it in cells normally resistant to infection, we made them easier to infect”.

Inhibiting this mechanism

The research team then succeeded in reproducing this mechanism by inhibiting the transferrin receptor 1 using a chemical molecule. ”We tested it successfully on human lung cells, on human lung tissue samples and on mice with several viral strains,” says Béryl Mazel-Sanchez. ”In the presence of this inhibitor, the virus replicated much less. However, in view of its potentially oncogenic characteristics, this product cannot be used to treat humans.” On the other hand, anti-cancer therapies based on the inhibition of the transferrin receptor are under development and could also be interesting in this context.

”Our discovery was made possible thanks to the excellent collaboration within the Faculty of Medicine as well as with the University Hospitals of Geneva (HUG) and the Swiss Institute of Bioinformatics (SIB),” the authors add. In addition to the transferrin receptor 1, scientists have identified some 30 other proteins whose role in the influenza A entry process remains to be deciphered. It is indeed likely that the virus uses a combination involving other receptors. ”Although we are still far from a clinical application, blocking the transferrin receptor 1 could become a promising strategy for treating influenza virus infections in humans and potentially in animals.”

Source:

University of Geneva

Journal reference:

Mazel-Sanchez, B., et al. (2023) Influenza A virus exploits transferrin receptor recycling to enter host cells. PNAS. doi.org/10.1073/pnas.2214936120.

Microbiome

You are what you excrete

25 May, 2023 Admin Leave a comment

Privacy is a concern in human microbiome research. Identifying an individual using microbial DNA present in a sample that they provide is predicated on the relative stability of any given microbiome, its uniqueness to an individual, and the nature of the residual microorganisms that we leave in the environment. A growing body of evidence suggests that these three features of microbiomes could be exploited for forensic applications^1,2,3. However, any human sample collected for microbiome analysis contains more than just microorganisms, because we shed human cells constantly, and human DNA sequences are often present in microbiome datasets. To allay privacy concerns in the National Institutes of Health’s Human Microbiome Project, removal methods for human DNA reads were pioneered⁴. These methods use computational screening of sequences against a human reference genome to identify and remove them. Although such methods are in use today, we need a comprehensive database to capture the unique variation that exists among human populations to be certain that all human DNA sequences have been removed. Such a database does not exist. Now writing in Nature Microbiology, Okada and colleagues⁵ report that there is substantial potential for identification of participants using metagenomes sequenced from human faecal samples.

Guccione, C., McDonald, D., Fielding-Miller, R. et al. You are what you excrete.
Nat Microbiol (2023). https://doi.org/10.1038/s41564-023-01395-x

Microbiology

How superbug A. baumannii survives metal stress and resists antibiotics

22 May, 2023 Admin Leave a comment

The deadly hospital pathogen Acinetobacter baumannii can live for a year on a hospital wall without food and water. Then, when it infects a vulnerable patient, it resists antibiotics as well as the body’s built-in infection-fighting response. The World Health Organization (WHO) recognises it as one of the three top pathogens in critical need of new antibiotic therapies.

Now, an international team, led by Macquarie University researchers Dr. Ram Maharjan and Associate Professor Amy Cain, have discovered how the superbug can survive harsh environments and then rebound, causing deadly infections. They have found a single protein that acts as a master regulator. When the protein is damaged, the bug loses its superpowers allowing it to be controlled, in a lab setting. The research is published in Nucleic Acids Research.

“We hope that our paper will encourage researchers worldwide to refocus on developing drugs to fight this superbug, which is spreading through the world’s hospitals, and killing already vulnerable people in intensive care units and other high-risk areas,” says Associate Professor Cain, the senior author on the paper.

There are six superbugs that scare global health officials. E. coli, Klebsiella pneumoniae and other gram-negative bacteria have common pathways that give them antibiotic resistance. A. baumannii is different. It’s particularly tough, and it’s one of the most resistant pathogens we encounter. Strangely, we don’t know much about how it infects us.

Breakthrough in a research challenge

“In the lab we can see this pathogen is very tough. Other researchers have shown that you can desiccate the bug for a year and when they added water, it was still able to infect mice,” says Associate Professor Cain.

“The problem had been that A. baumannii is relatively new on the scene, emerging as a problem in hospitals in the 1980s. And it’s hard to genetically manipulate with the existing molecular biology toolkit. It usually only infects sick people, but it is very resistant to antibiotics making it incredibly hard to treat and difficult to safely research. So, we don’t know much about it. We don’t know where it came from, nor how it became so resistant and resilient. Now, thanks to this paper, we know how it deals with stress.”

Amy and her colleagues realised about five years ago that they could make a difference by trying to understand the underlying biology of A. baumannii. That led to a major investment by Macquarie University in the research, in biocontainment laboratories for staff safety, and in an ethical animal model using moth caterpillars. The research effort has been strongly supported by the Australian Council and the National Health and Medical Research Council.

“We hope that our paper will encourage researchers worldwide to refocus on developing drugs to fight this superbug, which is spreading through the world’s hospitals.”

During infection our cells fight back by either flooding or starving bacteria of essential metals such as copper and zinc. A. baumannii has strong drug pumps that push antibiotics, metals and other threats out of the cell.

“By studying how this bug deals with infection stresses, we’ve found an important uncharacterised regulatory protein (DksA). When we disrupt this protein, it leads to changes in about 20 per cent of the bug’s genome and breaks its pumping system,” says Dr Ram Maharjan, a Macquarie University researcher and first author on the paper.

Not only does this protein control stress response, but it also controls virulence. A. baumannii usually spreads in blood but our disruption also caused it to be completely undetected in the blood of both Galleria mellonella and mice. It also becomes super sticky and harmlessly sticks to organs.

This has been a massive global research effort over the past five years, working with colleagues at Flinders University, Monash University, University of Cambridge, University of Wurzburg.

Ram P Maharjan, Geraldine J Sullivan, Felise G Adams, Bhumika S Shah, Jane Hawkey, Natasha Delgado, Lucie Semenec, Hue Dinh, Liping Li, Francesca L Short, Julian Parkhill, Ian T Paulsen, Lars Barquist, Bart A Eijkelkamp, Amy K Cain. DksA is a conserved master regulator of stress response in Acinetobacter baumannii. Nucleic Acids Research, 2023; DOI: 10.1093/nar/gkad341

Macquarie University

Microbiology

Predict what a mouse sees by decoding brain signals

5 May, 2023 Admin Leave a comment

Is it possible to reconstruct what someone sees based on brain signals alone? The answer is no, not yet. But EPFL researchers have made a step in that direction by introducing a new algorithm for building artificial neural network models that capture brain dynamics with an impressive degree of accuracy.

Rooted in mathematics, the novel machine learning algorithm is called CEBRA (pronounced zebra), and learns the hidden structure in the neural code.

What information the CEBRA learns from the raw neural data can be tested after training by decoding — a method that is used for brain-machine-interfaces (BMIs) — and they’ve shown they can decode from the model what a mouse sees while it watches a movie. But CEBRA is not limited to visual cortex neurons, or even brain data. Their study also shows it can be used to predict the movements of the arm in primates, and to reconstruct the positions of rats as they freely run around an arena. The study is published in Nature.

“This work is just one step towards the theoretically-backed algorithms that are needed in neurotechnology to enable high-performance BMIs,” says Mackenzie Mathis, EPFL’s Bertarelli Chair of Integrative Neuroscience and PI of the study.

For learning the latent (i.e., hidden) structure in the visual system of mice, CEBRA can predict unseen movie frames directly from brain signals alone after an initial training period mapping brain signals and movie features.

The data used for the video decoding was open-access through the Allen Institute in Seattle, WA. The brain signals are obtained either directly by measuring brain activity via electrode probes inserted into the visual cortex area of the mouse’s brain, or using optical probes which consist of using genetically modified mice, engineered so that activated neurons glow green. During the training period, CEBRA learns to map the brain activity to specific frames. CEBRA performs well with less than 1% of neurons in the visual cortex, considering that, in mice, this brain area consists of roughly 0.5 million neurons.

“Concretely, CEBRA is based on contrastive learning, a technique that learns how high-dimensional data can be arranged, or embedded, in a lower-dimensional space called a latent space, so that similar data points are close together and more-different data points are further apart,” explains Mathis. “This embedding can be used to infer hidden relationships and structure in the data. It enables researchers to jointly consider neural data and behavioral labels, including measured movements, abstract labels like “reward,” or sensory features such as colors or textures of images.”

“CEBRA excels compared to other algorithms at reconstructing synthetic data, which is critical to compare algorithms,” says Steffen Schneider, the co-first author of the paper. “Its strengths also lie in its ability to combine data across modalities, such as movie features and brain data, and it helps limit nuances, such as changes to the data that depend on how they were collected.”

“The goal of CEBRA is to uncover structure in complex systems. And, given the brain is the most complex structure in our universe, it’s the ultimate test space for CEBRA. It can also give us insight into how the brain processes information and could be a platform for discovering new principles in neuroscience by combining data across animals, and even species.” says Mathis. “This algorithm is not limited to neuroscience research, as it can be applied to many datasets involving time or joint information, including animal behavior and gene-expression data. Thus, the potential clinical applications are exciting.”

Steffen Schneider, Jin Hwa Lee, Mackenzie Weygandt Mathis. Learnable latent embeddings for joint behavioural and neural analysis. Nature, 2023; DOI: 10.1038/s41586-023-06031-6

Ecole Polytechnique Fédérale de Lausanne

Microbiology

Reconstructing ancient bacterial genomes can revive previously unknown molecules – offering a potential source for new antibiotics

4 May, 2023 Admin Leave a comment

Microorganisms – in particular bacteria – are skillful chemists that can produce an impressive diversity of chemical compounds known as natural products. These metabolites provide the microbes major evolutionary advantages, such as allowing them to interact with one another or their environment and helping defend against different threats. Because of the diverse functions bacterial natural products have, many have been used as medical treatments such as antibiotics and anti-cancer drugs.

The microbial species alive today represent only a tiny fraction of the vast diversity of microbes that have inhabited Earth over the past 3 billion years. Exploring this microbial past presents exciting opportunities to recover some of their lost chemistry.

Directly studying these metabolites in archaeological samples is virtually impossible because of their poor preservation over time. However, reconstructing them using the genetic blueprints of long-dead microbes could provide a path forward.

We are a team of anthropologists, archaeogeneticists and biochemists who study ancient microbes. By generating previously unknown chemical compounds from the reconstructed genomes of ancient bacteria, our newly published research provides a proof of concept for the potential use of fossil microbes as a source of new drugs.

The cellular machinery producing bacterial natural products is encoded in genes that are typically in close proximity to one another, forming what are called biosynthetic gene clusters. Such genes are difficult to detect and reconstruct from ancient DNA because very old genetic material breaks down over time, fragmenting into thousands or even millions of pieces. The end result is numerous tiny DNA fragments less than 50 nucleotides long all mixed together like a jumbled jigsaw puzzle.

We sequenced billions of such ancient DNA fragments, then improved a bioinformatic process called de novo assembly to digitally order the ancient DNA fragments in stretches of up to 100,000 nucleotides long – a 2,000-fold improvement. This process allowed us to identify not only what genes were present, but also their order in the genome and the ways they differ from bacterial genes known today – key information to uncovering their evolutionary history and function.

This method allowed us to take an unprecedented look at the genomes of microbes living up to 100,000 years ago, including species not known to exist today. Our findings push back the previously oldest reconstructed microbial genomes by more than 90,000 years.

In the microbial genomes we reconstructed from DNA extracted from ancient tooth tartar, we found a gene cluster that was shared by a high proportion of Neanderthals and anatomically modern humans living during the Middle and Upper Paleolithic that lasted from 300,000 to 12,000 years ago. This cluster bore the molecular hallmarks of very ancient DNA and belonged to the bacterial genus Chlorobium, a group of green sulfur bacteria capable of photosynthesis.

We inserted a synthetic version of this gene cluster into a “modern” bacterium called Pseudomona protegens so it could produce the chemical compounds encoded in the ancient genes. Using this method, we were able to isolate two previously unknown compounds we named paleofuran A and B and determine their chemical structure. Resynthesizing these molecules in the lab from scratch confirmed their structure and allowed us to produce larger quantities for further analysis.

By reconstructing these ancient compounds, our findings highlight how archaeological samples could serve as new sources of natural products.

Microbes are constantly evolving and adapting to their surrounding environment. Because the environments they inhabit today differ from those of their ancestors, microbes today likely produce different natural products than ancient microbes from tens of thousands of years ago.

As recently as 25,000 to 10,000 years ago, the Earth underwent a major climate shift as it transitioned from the colder and more volatile Pleistocene Epoch to the warmer and more temperate Holocene Epoch. Human lifestyles also dramatically changed over this transition as people began living outside of caves and increasingly experimented with food production. These changes brought them into contact with different microbes through agriculture, animal husbandry and their new built environments. Studying Pleistocene-era bacteria may yield insights into bacterial species and biosynthetic genes no longer associated with humans today, and perhaps even microbes that have gone extinct.

While the amount of data collected by scientists on biological organisms has exponentially increased over the past few decades, the number of new antibiotics has stagnated. This is particularly problematic when bacteria are able to evade existing antibiotic treatments faster than researchers can develop new ones.

By reconstructing microbial genomes from archaeological samples, scientists can tap into the hidden diversity of natural products that would have otherwise been lost over time, increasing the number of potential sources from which they can discover new drugs.

Our study has shown that it is possible to access natural products from the past. To tap into the vast diversity of chemical compounds encoded in ancient DNA, we now need to streamline our methodology to be less labor-intensive.

We are currently optimizing and automating our process to identify biosynthetic genes in ancient DNA more quickly and reliably. We are also implementing robotic liquid handling systems to complete the time-consuming pipetting and bacterial cultivation steps in our methods. Our goal is to scale up the process to be able to translate a vast amount of data on ancient microbes into the discovery of new therapeutic agents.

Although we can recreate ancient molecules, their biological and ecological roles are difficult to decipher. Since the bacteria that originally produced these compounds no longer exist, we cannot culture or genetically manipulate them. Further study will need to rely on similar bacteria that can be found today. Whether or not the functions of these compounds have remained the same in the modern relatives of ancient microbes remains to be tested. Although the original functions of these compounds for ancient microbes may be unknown, they still have the potential to be repurposed to treat modern diseases.

Ultimately, we aim to shed new light on microbial evolution and fight the current antibiotic crisis by providing a new time axis for antibiotic discovery.

Christina Warinner

Alexander Hübner

Pierre Stallforth

Microbiology

WPI-led team uncovers new details of SARS-COV-2 structure

31 March, 2023 Admin Leave a comment

A new study led by Worcester Polytechnic Institute (WPI) brings into sharper focus the structural details of the COVID-19 virus, revealing an elliptical shape that “breathes,” or changes shape, as it moves in the body. The discovery, which could lead to new antiviral therapies for the disease and quicker development of vaccines, is featured in the April edition of the peer-reviewed Cell Press structural biology journal Structure.

“This is critical knowledge we need to fight future pandemics,” said Dmitry Korkin, Harold L. Jurist ’61 and Heather E. Jurist Dean’s Professor of Computer Science and lead researcher on the project. “Understanding the SARS-COV-2 virus envelope should allow us to model the actual process of the virus attaching to the cell and apply this knowledge to our understanding of the therapies at the molecular level. For instance, how can the viral activity be inhibited by antiviral drugs? How much antiviral blocking is needed to prevent virus-to-host interaction? We don’t know. But this is the best thing we can do right now — to be able to simulate actual processes.”

Feeding genetic sequencing information and massive amounts of real-world data about the pandemic virus into a supercomputer in Texas, Korkin and his team, working in partnership with a group led by Siewert-Jan Marrink at the University of Groningen, Netherlands, produced a computational model of the virus’s envelope, or outer shell, in “near atomistic detail” that had until now been beyond the reach of even the most powerful microscopes and imaging techniques.

Essentially, the computer used structural bioinformatics and computational biophysics to create its own picture of what the SARS-COV-2 particle looks like. And that picture showed that the virus is more elliptical than spherical and can change its shape. Korkin said the work also led to a better understanding of the M proteins in particular: underappreciated and overlooked components of the virus’s envelope.

The M proteins form entities called dimers with a copy of each other, and play a role in the particle’s shape-shifting by keeping the structure flexible overall while providing a triangular mesh-like structure on the interior that makes it remarkably resilient, Korkin said. In contrast, on the exterior, the proteins assemble into mysterious filament-like structures that have puzzled scientists who have seen Korkin’s results, and will require further study.

Korkin said the structural model developed by the researchers expands what was already known about the envelope architecture of the SARS-COV-2 virus and previous SARS- and MERS-related outbreaks. The computational protocol used to create the model could also be applied to more rapidly model future coronaviruses, he said. A clearer picture of the virus’ structure could reveal crucial vulnerabilities.

“The envelope properties of SARS-COV-2 are likely to be similar to other coronaviruses,” he said. “Eventually, knowledge about the properties of coronavirus membrane proteins could lead to new therapies and vaccines for future viruses.”

The new findings published in Structure were three years in the making and built upon Korkin’s work in the early days of the pandemic to provide the first 3D roadmap of the virus, based on genetic sequence information from the first isolated strain in China.

Weria Pezeshkian, Fabian Grünewald, Oleksandr Narykov, Senbao Lu, Valeria Arkhipova, Alexey Solodovnikov, Tsjerk A. Wassenaar, Siewert J. Marrink, Dmitry Korkin. Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling. Structure, 2023; DOI: 10.1016/j.str.2023.02.006

Worcester Polytechnic Institute

Microbiology

Biologists, chemical engineers collaborate to reveal complex cellular process inside petunias

6 March, 2023 Admin Leave a comment

Once upon a time, prevailing scientific opinion might have pronounced recently published research in Nature Communications by a team of Purdue University scientists as unneeded. Now, climate change implications have heightened the need for this line of research.

Flowers emit scent chemicals called volatile organic compounds (VOCs). Earlier this year, the Purdue team published the paper identifying for the first time a protein that plays a key role in helping petunias emit volatiles. The article was selected for the “plants and agriculture” section of the journal’s editors’ highlights webpage.

Natalia Dudareva, who led the study, and her longtime collaborator John Morgan had suggested years ago in grant proposals that molecular processes could be involved in VOC emission. Both times the grant reviewers said there was nothing to look for because simple diffusion was the answer.

“We failed twice because people did not believe us,” said Dudareva, director of the Center for Plant Biology and Distinguished Professor of Biochemistry. “We decided we have to have proof that it’s not simple diffusion, that molecular mechanisms are involved.”

The new work builds on findings that the Dudareva-Morgan collaboration announced in 2015 and 2017 showing how biology helps control the release of scent compounds from plants. The latest paper, chiefly funded by the National Science Foundation and the U.S. Department of Agriculture, focuses on how volatiles cross the cell wall, the barrier that separates the cellular interior from a plant’s outermost protective layer, the cuticle.

“We were looking at whether or not there are proteins that facilitate the transport of these small organic molecules across the cell wall layer,” said Morgan, a professor of chemical engineering.

“The best analogy is to the transport of oxygen in muscle tissue by a protein called myoglobin.”

Volatile organic chemicals are small molecules that have low water solubility. The cell wall, however, is a water-filled environment. This slows the diffusion rate of VOCs because their concentrations cannot build up very high.

“What happens is a protein can bind a lot of these molecules inside a non-waterlike cavity, and it improves or increases the net transport rate,” Morgan explained.

The work has significant practical implications, ranging from the health of the planet to industrial operations. Plants now emit 10 billion metric tons of carbon annually, a quantity that will increase with continued global warming. Floral volatiles also help to protect plants against environmental stresses and are heavily used in the cosmetics industry and in aromatherapy.

“And our diet depends on insect-pollinated plants,” Dudareva said. With global warming, flowers may start blooming earlier, before insects are ready to begin pollination.

The team’s 2015 paper published in the journal Trends in Plant Science reported calculations that had determined the concentration of volatiles needed to sustain the experimentally measured floral emission rate. The concentration reached the millimolar range, a scale that chemists use to quantify substances containing huge numbers of molecules or atoms.

“These compounds will accumulate inside membranes and such high concentration will destroy membranes and destroy the cell,” Dudareva said. This left a clear-cut conclusion: simple diffusion would be impossible.

The initial work had been calculated for snapdragons. But the Purdue researchers focused on petunias for their latest study because, unlike snapdragons, they can be genetically modified to study how particular genes affect the emission process.

“It’s much easier to work with petunias because emission is high, especially during the night,” said Pan Liao, a lead co-author and former Purdue postdoctoral scientist, now an assistant professor of biology at Hong Kong Baptist University. “The emission is strongly regulated in a diurnal pattern.”

Additional co-authors were Itay Maoz, a former Purdue postdoctoral scientist now of Israel’s Agricultural Research Organization; Meng-Ling Shih, PhD 2022, chemical engineering; Xing-Qi Huang, a postdoctoral scientist working in Dudareva’s lab; and Ji Hee Lee, a graduate student in biochemistry. The co-authors contributed a complementary blend of skills and expertise to the work that has become a hallmark of the longstanding collaboration between the Dudareva and Morgan research groups.

Dudareva’s group generated the transgenic plants and handled the cellular biology needed to determine whether a given protein contributes to the volatile emissions. There is no way, however, to detect the level of proteins in a cell or how their concentration changes across a cell wall.

It then fell to Morgan’s group to perform the calculations that quantified the protein contributions and conduct computer simulations to verify the experimental data.

“It’s important to have feedback between the modeling predictions and the actual data,” Morgan said. “Sometimes it starts with the data, then we go do math, and then we go back and compare to the data.”

Pan Liao, Itay Maoz, Meng-Ling Shih, Ji Hee Lee, Xing-Qi Huang, John A. Morgan, Natalia Dudareva. Emission of floral volatiles is facilitated by cell-wall non-specific lipid transfer proteins. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36027-9

Purdue University

Microbiology

The pandemic virus SARS-CoV-2 continues to cause infections as it mutates into new variants. While the vaccines that …

4 February, 2023 Admin Leave a comment

The pandemic virus SARS-CoV-2 continues to cause infections as it mutates into new variants. While the vaccines that are available have been able to significantly reduce the likelihood that vaccinated people will be hospitalized or die from the virus, they have not been exceptionally good at preventing infection. The mRNA vaccines are also based on the spike protein, which has kept evolving as new variants have emerged, and protection is waning.

Researchers have been trying to develop a great vaccine for SARS-CoV-2 since the COVID-19 pandemic began, but traditional vaccines can take years to perfect, produce, and test. We were lucky to have access to mRNA technology that brought us vaccines quickly, but there is a lot of room for improvement.

New research reported in Science Translational Medicine has described a different approach to a SARS-CoV-2 vaccine that has taken inspiration from evolution of the virus. In this study, the investigators assessed he sequences of 11,650,487 SARS-CoV-2 samples. This revealed that the spike protein of the virus, which is used by the pathogen to latch onto and infect cells, has not experienced a random evolutionary trajectory. Instead, the virus has followed paths of either high infectivity with low immune resistance or low infectivity with high immune resistance.

The infectivity and immune resistance of SARS-CoV-2 variants tend to be incompatible, the researchers found, with the exception of the Beta and Kappa variants. Omicron exhibited the highest degree of immune resistance when it was tested in cell lines, and demonstrated high infectivity in one type of cell.

The researchers used this data to design a vaccine antigen called Span, which is aimed at multiple targets on the virus. The Span protein carries sequences that are consistently found in many viral variants throughout the evolution of the virus, so the vaccine should provide protection against many existing and emerging variants of SARS-CoV-2.

When tested in an animal model, the Span vaccine triggered the production of antibodies that could neutralize different variants of the SARS-CoV-2 virus, and was totally effective against mortality caused by Omicron. This study has highlighted how different vaccine designs can help keep people protected as the SARS-CoV-2 virus continues to evolve and cause new infections. This vaccine stil has to be tested in people, however.

Other teams of researchers are also working to develop different kinds of SARS-CoV-2 vaccines.

Source: Science Translational Medicine

Carmen Leitch

Microbiology

Smallpox, caused by the variola virus, is one of the worst diseases humanity has ever faced, and it …

11 January, 2023 Admin Leave a comment

Smallpox, caused by the variola virus, is one of the worst diseases humanity has ever faced, and it has many distinctions. The first vaccine that was ever developed was for smallpox, for example. It likely killed 300 million people or more before it was eliminated from circulation in an intensive campaign by the World Health Organization (WHO) and other institutions that began in 1967. The last known naturally occurring case happened in 1977 in Somalia. It is the only disease that humans have been able to completely eradicate.

The origins of smallpox are still a mystery. Historical records have suggested that smallpox has been affecting people for 3,500 years, while archaeovirology studies have indicated that the virus has been around for about 1,700 years.

A new study has now estimated that the variola virus emerged 3,800 years ago or more, and that it did infect people living in ancient societies. Pockmarks on Egyptian mummies support this claim. In this study, researchers compared the genomes of modern and historic variola strains, tracing the evolution of the virus through time. The work showed that different viral strains have evolved from a common ancestor. The findings have been reported in Microbial Genomics.

In 2020, a study of skeletons from the Viking era revealed genetic material from several variola virus strains. Previous genetic evidence had only dated the virus to about the year 1600, so the 2020 research showed that smallpox was circulating at least 1,000 years before that.

The researchers have also speculated about when the virus emerged. In viruses, there is a known evolutionary feature known as a “time-dependent rate phenomenon.” The rate of viral evolution depends on the timeframe that’s being considered; viruses will appear to change more rapidly in short time spans, and more slowly over long periods. The study authors accounted for this, and created an equation that allowed them to make an estimate, which agrees with historians that the virus emerged over 3,800 years ago. The scientists are hopeful that a controversy in these fields will now be resolved.

There are two main lineages of variola, which split from the ancestor prior to the development of a vaccine; these lineages seem to have arisen at a time when human population was increasing dramatically.

The researchers also suggested that the virus likely emerged in Africa or the Middle East. It may have originated in gerbils, who harbor the likely ancestor of smallpox, and the pockmarked mummies provide evidence of smallpox in Ancient Egypt.

“Variola virus may be much, much older than we thought. This is important because it confirms the historical hypothesis that smallpox existed in ancient societies. It is also important to consider that there are some aspects in the evolution of viruses that should be accounted for when doing this type of work,” noted first study author Dr. Diego Forni of the Eugenio Medea Scientific Institute (IRCCS E. Medea).

Sources: Microbiology Society, Microbial Genomics

Carmen Leitch

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