The most common organism in the oceans, and possibly on the entire planet, is a family of single-celled marine bacteria called SAR11. These drifting organisms look like tiny jelly beans and have evolved to outcompete other bacteria for scarce resources in the oceans.

We now know that this group of organisms thrives despite — or perhaps because of — the ability to host viruses in their DNA. A published in May in Nature Microbiology could lead to new understanding of viral survival strategies.

91Ě˝»¨ oceanographers discovered that the bacteria that dominate seawater, known as Pelagibacter or SAR11, hosts a unique virus. The virus is of a type that spends most of its time dormant in the host’s DNA but occasionally erupts to infect other cells, potentially carrying some of its host’s genetic material along with it.

“Many bacteria have viruses that exist in their genomes. But people had not found them in the ocean’s most abundant organisms,” said co-lead author , a 91Ě˝»¨associate professor of oceanography. “We suspect it’s probably common, or more common than we thought — we just had never seen it.”

This virus’ two-pronged survival strategy differs from similar ones found in other organisms. The virus lurks in the host’s DNA and gets copied as cells divide, but for reasons still poorly understood, it also replicates and is released from other cells.

The new study shows that as many as 3% of the SAR11 cells can have the virus multiply and split, or lyse, the cell — a much higher percentage than for most viruses that inhabit a host’s genome. This produces a large number of free viruses and could be key to its survival.

“There are 10 times more viruses in the ocean than there are bacteria,” Morris said. “Understanding how those large numbers are maintained is important. How does a virus survive? If you kill your host, how do you find another host before you degrade?”

The study could prompt basic research that could help clarify host–virus interactions in other settings.

“If you study a system in bacteria, that is easier to manipulate, then you can sort out the basic mechanisms,” Morris said. “It’s not too much of a stretch to say it could eventually help in biomedical applications.”

The 91Ě˝»¨oceanography group had published a previous paper in 2019 looking at how marine phytoplankton, including SAR11, use sulfur. That allowed the researchers to cultivate two new strains of the ocean-dwelling organism and analyze one strain, NP1, with the latest genetic techniques.

Co-lead author collected samples off the coast of Oregon during a research cruise. She diluted the seawater several times and then used a sulfur-containing substance to grow the samples in the lab — a difficult process, for organisms that prefer to exist in seawater.

The team then sequenced this strain’s DNA at the in Seattle.

“In the past we got a full genome, first try,” Morris said. “This one didn’t do that, and it was confusing because it’s a very small genome.”

The researchers found that a virus was complicating the task of sequencing the genome. Then they discovered a virus wasn’t just in that single strain.

“When we went to grow the NP2 control culture, lo and behold, there was another virus. It was surprising how you couldn’t get away from a virus,” said Cain, who graduated in 2019 with a 91Ě˝»¨bachelor’s in oceanography and now works in a 91Ě˝»¨research lab.

Cain’s experiments showed that the virus’ switch to replicating and bursting cells is more active when the cells are deprived of nutrients, lysing up to 30% of the host cells. The authors believe that bacterial genes that hitch a ride with the viruses could help other SAR11 maintain their competitive advantage in nutrient-poor conditions.

“We want to understand how that has contributed to the evolution and ecology of life in the oceans,” Morris said.

Co-authors are postdoctoral researcher and associate professor in the 91Ě˝»¨Department of Biochemistry. The study was funded by the National Science Foundation and the National Institutes of Health’s National Institute of Allergy and Infectious Disease.

For more information, contact Morris at morrisrm@uw.edu or 206-221-7228 and Cain at kcain97@uw.edu.

A team of chemical engineers has developed a new way to produce medicines and chemicals and preserve them using portable “biofactories” embedded in water-based gels known as hydrogels. The approach could help people in remote villages or on military missions, where the absence of pharmacies, doctor’s offices or even basic refrigeration makes it hard to access critical medicines and other small-molecule compounds.

The team — led by , a professor of chemical engineering at the University of Texas, and , an assistant professor of chemistry at the 91Ě˝»¨ — describes the new approach in a published Feb. 4 in Nature Communications.

“We expect these developments to afford new technologies for on-demand production of small-molecule and peptide products in the future,” said Nelson, who is also a faculty member in the 91Ě˝»¨, in a accompanying the paper. “This technology will be especially applicable in remote or isolated areas where space and resources are limited, which could include manned space missions or personalized medications.”

Their system effectively embeds microbial biofactories — cells engineered to overproduce a product — into the solid scaffold of a hydrogel, allowing for portability and optimized production. It is the first hydrogel-based system to organize both individual microbes and consortia for in-the-moment production of high-value chemical feedstocks, used for processes such as fuel and pharmaceutical production. Products can be produced within a couple of hours to a couple of days.

“Many of the chemicals, fuels, nutraceuticals and pharmaceuticals we use rely on traditional fermentation technology,” said Alper. “Our technology addresses a strong limitation in the fields of synthetic biology and bioprocessing, namely the ability to provide a means for both on-demand and repeated-use production of chemicals and antibiotics from both mono- and co-cultures.”

As a crosslinked polymer, the hydrogel used in this work can be 3D printed or manually extruded. The gel material, along with the cells inside, can flow like a liquid and then harden upon exposure to UV light. The resulting polymer network is large enough for molecules and proteins to move through it, but the space is too small for cells to leak out.

The team also found that by freeze-drying the hydrogel system, it can effectively preserve the fermentation capacity of the biofactories until needed in the future. The result of the freeze-drying somewhat resembles an ancient mummy, shriveled up but well-preserved. To revive the hydrogel, the researchers simply added water, sugar and other basic nutrients, and the cells could resume production just as effectively as before the preservation process.

One of the novel applications enabled by this platform is the ability to combine multiple different organisms, called consortia, together in a way that outperforms traditional, large-scale bioreactors. In particular, this system enables a plug-and-play approach to combining and optimizing chemical production. For example, if one set of enzymes works best in the bacteria E. coli, while the other works best in budding yeast, the two organisms can work together to more efficiently go straight to the product. The research team tested both of these organisms.

This platform has the added benefit of multitasking, keeping different types of cells separated while they grow, preventing one from taking over and killing off the others. Likewise, by testing a range of temperatures, the team could control the dynamics of the system, keeping the growth of multiple cell types balanced.

Finally, the team showed continuous, repeated use of the system — with yeast cells — over the course of an entire year without a decrease in yields, indicating the sustainability of the process over time.

Medicines such as antibiotics have a fixed shelf life and require specific storage conditions. The portability of a biofactory that can synthesize these molecules makes the hydrogel system especially useful in remote places that don’t have access to refrigeration to store medications. It would also be a small and compact way to maintain access to several medications and other essential chemicals when there is no access to a pharmacy or a store, like during a military mission or a mission to Mars. Although not quite there yet, the possibilities are promising.

“This technology can be applied to a wide range of products and cell types. We see engineers and scientists being able to plug and play with different consortia of cells to produce diverse products that are needed for a specific scenario,” Alper said. “That’s part of what makes this technology so exciting.”

Co-lead authors on the paper are 91Ě˝»¨graduate student Trevor Johnston and University of Texas graduate student Shuo-Fu Yuan. Co-authors are James Wagner and Xiunan Yi at the University of Texas, former 91Ě˝»¨postdoctoral researcher Abhijit Saha, and 91Ě˝»¨graduate student Patrick Smith. The research was funded by the Camille and Henry Dreyfus Foundation, the 91Ě˝»¨ and the Royalty Research Fund.

For more information contact Nelson at alshakim@uw.edu.

Adapted from a by the University of Texas news office.

“Thinking of arsenic as not just a bad guy, but also as beneficial, has reshaped the way that I view the element,” said first author , who did the research for her doctoral thesis at the 91Ě˝»¨and is now a postdoctoral fellow at the Woods Hole Oceanographic Institution and the Massachusetts Institute of Technology.

The was published this week in the .

“We’ve known for a long time that there are very low levels of arsenic in the ocean,” said co-author , a 91Ě˝»¨professor of oceanography. “But the idea that organisms could be using arsenic to make a living — it’s a whole new metabolism for the open ocean.”

The researchers analyzed seawater samples from a region below the surface where oxygen is almost absent, forcing life to seek other strategies. These regions may expand under climate change.

“In some parts of the ocean there’s a sandwich of water where there’s no measurable oxygen,” Rocap said. “The microbes in these regions have to use other elements that act as an electron acceptor to extract energy from food.”

The most common alternatives to oxygen are nitrogen or sulfur. But Saunders’ early investigations suggested arsenic could also work, spurring her to look for the evidence.

The team analyzed samples collected during a 2012 research cruise to the tropical Pacific, off the coast of Mexico. Genetic analyses on DNA extracted from the seawater found two genetic pathways known to convert arsenic-based molecules as a way to gain energy. The genetic material was targeting two different forms of arsenic, and authors believe that the pathways occur in two organisms that cycle arsenic back and forth between different forms.

Results suggest that arsenic-breathing microbes make up less than 1% of the microbe population in these waters. The microbes discovered in the water are probably distantly related to the arsenic-breathing microbes found in hot springs or contaminated sites on land.

“What I think is the coolest thing about these arsenic-respiring microbes existing today in the ocean is that they are expressing the genes for it in an environment that is fairly low in arsenic,” Saunders said. “It opens up the boundaries for where we could look for organisms that are respiring arsenic, in other arsenic-poor environments.”

Biologists believe the strategy is a holdover from Earth’s early history. During the period when life arose on Earth, oxygen was scarce in both the air and in the ocean. Oxygen became abundant in Earth’s atmosphere only after photosynthesis became widespread and converted carbon dioxide gas into oxygen.

Early lifeforms had to gain energy using other elements, such as arsenic, which was likely more common in the oceans at that time.

“We found the genetic signatures of pathways that are still there, remnants of the past ocean that have been maintained until today,” Saunders said.

Arsenic-breathing populations may grow again under climate change. Low-oxygen regions are projected to expand, and dissolved oxygen is predicted to drop throughout the marine environment.

“For me, it just shows how much is still out there in the ocean that we don’t know,” Rocap said.

Saunders recently collected more water samples from the same region and is now trying to grow the arsenic-breathing marine microbes in a lab in order to study them more closely.

“Right now we’ve got bits and pieces of their genomes, just enough to say that yes, they’re doing this arsenic transformation,” Rocap said. “The next step would be to put together a whole genome and find out what else they can do, and how that organism fits into the environment.”

Co-author collected the samples and led the DNA sequencing effort as a 91Ě˝»¨postdoctoral research scientist and now holds a faculty position at the University of Maryland. The other co-author is , a research scientist in the 91Ě˝»¨School of Oceanography. The study was funded by a graduate fellowship from NASA and a research grant from the National Science Foundation.

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For more information, contact Saunders at jaci@whoi.edu or Rocap at 206-685-9994 or rocap@uw.edu.

When it comes to the well-being of coral reefs, for many years scientists focused on , an event that can endanger corals and the diverse marine ecosystems that they support. In bleaching, high temperatures or other stressors cause corals to expel Symbiodinium, the beneficial, brightly colored microbes that would normally share excess energy and nutrients with corals. Bleaching ultimately starves corals and endangers the entire reef ecosystem.

But over the last two decades, scientists have realized that other microbes are also critical for coral health, including communities of bacteria that live on coral surfaces and in their tissues. These bacteria constitute the coral microbiome. High temperatures — even below the threshold for bleaching — can coral microbiomes, leaving corals .

But scientists lack comprehensive data about the bacteria that make up the microbiomes of the more than 1,500 coral species worldwide. That is starting to change thanks to the , a collaboration among researchers at the 91Ě˝»¨ Bothell, Pennsylvania State University and Oregon State University. The team is studying the diversity of bacteria within corals and how it has changed over time.

In their first comprehensive survey of healthy corals, Nov. 22 in the journal , the team reports that coral bacteria are a surprisingly diverse bunch — and that different sections of the coral body can host unique communities of bacteria.

“This project represents one of the most comprehensive efforts to identify what kinds of bacteria are present in diverse groups of tropical corals, how the types of bacteria can differ over coral anatomy, and how the symbiotic relationships between corals and bacteria have changed over coral evolution,” said senior and corresponding author , an assistant professor of biological sciences at 91Ě˝»¨Bothell.

Their findings reveal what a relatively healthy coral microbiome looks like in a variety of coral species, and how coral microbiomes have formed and evolved. Understanding the microbiome may even help predict which corals will survive heat waves or disease outbreaks.

“Just like the bacteria within our gut help us digest food and protect us from pathogens, the normal bacteria associated with corals can also help them process nutrients and help protect them against disease,” said Zaneveld.

The team partnered with scientists at James Cook University and the Australian Institute of Marine Science to collect 691 small tissue samples from 236 different healthy corals along the Great Barrier Reef. The researchers took samples from up to three different tissues in each coral: the hard skeleton of calcium carbonite, the soft inner tissue and the outer mucus layer. The corals sampled included diverse species that have, in some cases, been evolving separately for tens of millions of years.

The researchers sequenced sections of DNA from bacteria in those tissue samples, which they used to identify the types of bacteria in healthy microbiomes for each coral species and tissue. They discovered that the mucus, skeleton and soft tissue all contain distinct microbial communities — and that the richness and diversity of bacterial species present differed greatly by tissue type. In general, the skeleton contained the greatest diversity of bacteria, a finding which surprised the team. They had been expecting the mucus, which coats the coral and forms a barrier between itself and the environment, to harbor the most diverse microbiome. Instead, the mucus microbiome was often the least diverse.

The team also discovered that coral species differed the most in the composition of their tissue microbiomes. While mucus microbiomes also differed by coral species, they were also strongly influenced by environmental factors such as location, temperature and depth. The major differences between coral species raised questions about the age of these associations between corals and their microbes, and how they have changed over time.

The researchers found that distantly related corals were more likely to have highly different microbiomes. Corals that were more closely related typically had similar microbiomes. This pattern, known as , was strongest for the microbiomes from inside the corals’ stony skeletons. Though the team discovered that many coral-bacteria associations are likely recent, at least four types of bacteria evolved together with certain groups of corals over millions of years.

Now the researchers hope to gather additional data on healthy coral microbiomes to learn why some species have strikingly different types of microbiomes and to investigate how tissues in the same coral establish and maintain different microbiomes.

“We want to understand what roles that different factors — such as the coral’s immune system or its environment — play in shaping the microbiome,” said Zaneveld. “These answers could help us understand how the microbiome affects coral health, and what goes wrong when the corals are stressed.”

Stony corals have been around for more than 400 million years, and today’s coral reefs shelter fish that and harbor . Stressors linked to climate change are already linked to . But simply studying coral microbiomes will not save reefs, Zaneveld said.

“The Great Barrier Reef is huge — roughly twice the size of the state of Washington — so there is probably no drug or beneficial microbe we can add to the water to save it,” said Zaneveld. “But, we can save coral reefs by fighting back against climate change.”

Only tackling the root causes of coral reef decline — through measures to slow climate change and reduce both overfishing and nutrient pollution — will ultimately help corals, he said.

“And if we do, we can also save intricate bacterial symbioses that evolved over millions of years, and that may hold the key to new medical drugs that we would otherwise lose from the world forever,” said Zaneveld.

Co-lead authors of the paper are postdoctoral researchers F. Joseph Pollock at Pennsylvania State University and Ryan McMinds at Oregon State University. Co-authors are Styles Smith and MĂłnica Medina at Pennsylvania State University; David Bourne at James Cook University and the Australian Institute of Marine Science; Bette Willis at James Cook University; and Rebecca Vega Thurber at Oregon State University. The research was funded by the National Science Foundation.

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For more information, contact Zaneveld at 425-352-3789 or zaneveld@uw.edu.

Grant number: 1442306

This microbiological version of the “” is a new paradigm suggested by scientists at the 91Ě˝»¨ Bothell and Oregon State University. It may suggest who would benefit most from screens to identify the microbes that reside in their gut, with implications for drug therapy, management of chronic diseases and other aspects of medical care.

On Aug. 24, the researchers published a in outlining their adaptation of the Anna Karenina principle for the microbial realm. The principle gets its name from the opening line of the novel “Anna Karenina” by Leo Tolstoy: “All happy families are alike; each unhappy family is unhappy in its own way.”

It turns out that this observation applies to perturbed microbiotas of humans and animals. When these microbiotas are unhappy, each is unhappy in its own way.

“This line of thinking started with studies of the microbiology of threatened corals,” said lead and corresponding author , an assistant professor of biological sciences at 91Ě˝»¨Bothell. “We found that several stressors made the types of bacteria on corals more variable, allowing blooms of different harmful bacteria on each coral.”

“We were struck by similarities to HIV/AIDs. After HIV suppresses the immune system, patients become vulnerable to opportunistic pathogens — but you can’t predict which one will infect any particular patient. It turns out that this microbial variation is a pattern common to many — though certainly not all — stressors and diseases, and occurs in helpful microbes as well as harmful ones.”

Before joining the 91Ě˝»¨Bothell faculty, Zaneveld was a postdoctoral researcher at OSU, working with assistant professor of microbiology . It was there that they formulated the idea that microbial communities might behave more in line with Tolstoy’s words than scientists had previously thought.

“When microbiologists have looked at how microbiomes change when their hosts are stressed from any number of factors — temperature, smoking, diabetes, for example — they’ve tended to assume directional and predictable changes in the community,” said Vega Thurber, who is also a corresponding author on the perspective. “After tracking many datasets of our own we rarely seemed to find this pattern but rather found a distinct one where microbiomes actually change in a stochastic, or random, way.”

Zaneveld and Vega Thurber worked with OSU doctoral student to survey the academic and research literature on microbial changes caused by perturbation. They found those stochastic — or random — changes to be a common occurrence, but one that researchers have tended to discard or bury deep in supplementary materials, rather than highlight in their reports.

“What’s amazing is how obvious these Anna Karenina principle effects are — if you’re looking for them — and how easy they are to miss if you’re searching for a more conventional pattern,” said Zaneveld. “When researchers have reported them, they’ve often assumed that they are a unique quirk of the microbiology of their disease of interest, rather than a more general phenomenon.”

Their work drew together diverse ideas and experiments from microbiome research — including observations from humans and other animals and across multiple human diseases. They propose new methods for analyzing microbiome data to identify situations where the Anna Karenina principle might be at work.

“When healthy, our microbiomes look alike, but when stressed each one of us has our own microbial ‘snowflake,'” said Vega Thurber. “You or I could be put under the same stress, and our microbiomes will respond in different ways — that’s a very important facet to consider for managing approaches to personalized medicine. Stressors like antibiotics or diabetes can cause different people’s microbiomes to react in very different ways.”

Humans and animals are filled with symbiotic communities of microorganisms that often fill key roles in normal physiological function and also influence susceptibility to disease. Predicting how these communities of organisms respond to perturbations — anything that alters the systems’ function — is one of microbiologists’ essential challenges.

Studies of microbiome dynamics have typically looked for patterns that shift microbiomes from a healthy, stable state to a “dysbiotic,” stable state; dysbiosis refers to any unusual configuration of the microbiome with negative consequences for the health of the host. By the Anna Karenina principle, the microbial communities of dysbiotic individuals vary more in composition than in healthy individuals.

The researchers found patterns consistent with Anna Karenina effects in other systems as well, such as the lungs of smokers. Since microbiomes also influence how patients respond to medical drugs, conditions that make the microbiome more variable — such as inflammatory bowel disorders — may also make more variable patients’ responses to drugs from digoxin to asprin.

But, to consider and test these possibilities, scientists must first discuss the Anna Karenina effect among themselves.

“This is the start of a conversation, and not all diseases will show these patterns,” said Zaneveld. “But when you see the same pattern everywhere — from corals enduring high temperatures to wild chimpanzees with suppressed immunity — it suggests we should pay very close attention to the mechanisms that produce it.”

“I hope that by drawing together these research findings from diverse areas, we accelerate the development of common tools and language to understand the role of chance in shaping the microbial part of ourselves.”

The research was funded by the National Science Foundation.

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For more information, contact Zaneveld at 425-352-3789 or zaneveld@uw.edu and Vega Thurber at 541-737-185 or Rebecca.Vega-Thurber@oregonstate.edu.

Adapted from by the OSU .

These are , a diverse group of organisms that includes microalgae, viruses, bacteria and archaea. They serve as the base of the marine food chain and are responsible for controlling much of the ocean’s nutrient flow and health.

But given their prevalence, very little is known about how they interact and carry out fundamental processes in the ocean, particularly in deep, low-oxygen waters where the impacts of climate change are becoming significant. In these areas, up to half of all available nitrogen — a nutrient that is essential for all ocean life — is lost due to microbial processes on overdrive because of warmer ocean water and less circulation.

Now, a 91Ě˝»¨ team has on a common but poorly understood bacteria known to live in these areas. By culturing and sequencing the microbe’s entire genome, the oceanographers found that it significantly contributes to the removal of life-supporting nitrogen from the water in new and surprising ways.

“If we want to understand how the oceans are working and be able to model them in any sort of predictive way, we need to more accurately understand what the inputs and outputs are,” said senior author , a 91Ě˝»¨associate professor of oceanography. “This is an important organism that fixes carbon, is involved in nitrogen loss and is in parts of the ocean that are shifting due to climate change. We now have the first-ever culture in the laboratory and we can study its physiology.”

The were published July 19 in the , a Nature publication.

This organism, given the name Candidatus Thioglobus autotrophicus, is present in low-oxygen waters around the world and is one of the dominant organisms in these areas — between 40 and 60 percent of all cells in some regions.

Living things use oxygen for their metabolic activities, but in low-oxygen areas, bacteria and archaea have evolved to “breathe” other elements available in seawater. One of those is a chemical called nitrate which, when respired, produces gaseous nitrogen. That gas escapes to the atmosphere, effectively leaving the ocean and removing valuable nitrogen from the water.

The bacteria grown and sequenced by the 91Ě˝»¨oceanographers have been pegged as playing a big role in removing nitrogen from the ocean, but until now scientists didn’t have a complete picture of how it happened.

“We are filling in the gaps by providing a full genome,” said lead author , a 91Ě˝»¨doctoral student in oceanography. “Now we can talk about both what these organisms can and can’t do.”

The research team confirmed the bacteria are contributing to nitrogen loss, but in a different way than expected. More specifically, they are responsible for a key step — converting nitrate to a similar chemical called nitrite — which then goes on to fuel other nitrogen-removal processes. Earlier research had hypothesized that these microbes also produce ammonia, another nitrogen-containing chemical. Instead, the 91Ě˝»¨team found that the microbes consume ammonia, essentially competing with other organisms for this nitrogen compound that is also important for growth and development.

At a global scale, the areas of the ocean where these bacteria live are getting bigger as climate change creates conditions that produce low-oxygen zones, including warmer ocean temperatures and less water circulation.

“In the very big picture, we know that different types of oxygen minimum zones that house these organisms are getting bigger and more persistent,” Shah said. “So, whatever influence these bugs have on water chemistry and the atmosphere is going to get more and more important — basically, their habitat is expanding.”

Growing this organism in the lab was no easy task. The 91Ě˝»¨oceanographers combined several techniques to culture the bacteria in as close as possible to their native ocean environment. It took almost a year to stabilize them to the point where researchers could start doing physiological experiments.

Even the experiments, however, took more time than usual, because these organisms grow much slower than most cultures grown in the lab.

“Most experiments lasted 10 to 15 days because they were growing so slowly. But the advantage is they are actually behaving very similarly to how they do in the ocean environment,” Morris said.

Shah collected the organism from a low-oxygen fjord off the coast of British Columbia from the R/V Thomas G. Thompson during a . She then used these organisms to grow identical offspring in the lab.

The researchers will look next at the role this bacteria play in the ocean’s carbon and sulfur cycles. They also recently received National Science Foundation funding to study this organism and its relatives in other low-oxygen areas around the world, including off the coast of Mexico.

of the UW’s Joint Institute for the Study of the Atmosphere and Ocean is a co-author on this study. The work was funded by the National Science Foundation, the 91Ě˝»¨Royalty Research Fund and the .

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For more information, contact Morris at morrisrm@uw.edu or 206-221-7228 and Shah at vs1@uw.edu or 206-685-4118.

Grant numbers: OCE-1232840, DGE-1068839

But until recently, scientists interested in these single-celled creatures knew next to nothing about their genes.

91Ě˝»¨ scientists have sequenced the complete genetic makeup of one of these algae. As they recently reported , it is only the second time that researchers have sequenced the genome of one of these ecologically important and plentiful algae, known as . Researchers hope to better understand haptophytes and perhaps transform them into an important new tool for aquaculture, biofuel production and nutrition.

“Haptophytes are really important in carbon dioxide management and they form a critical link in the aquatic foodchain,” said senior author and 91Ě˝»¨biology professor . “This new genome shows us so much about this group.”

The haptophyte Cattolico and her team studied is Chrysochromulina tobin, and it thrives in oceans across the globe. The researchers spent years on a series of experiments to sequence all of Chrysochromulina‘s genes and understand how this creature turns different genes on and off throughout the day. In the process, they discovered that Chrysochromulina would make an ideal subject for investigating how algae make fat, a process important for nutrition, ecology and biofuel production.

“It turns out that their fat content gets high during the day and goes down during the night,” said Cattolico. “A very simple pattern, and ideal for follow-up.”

She believes that that these extreme changes in fat content — even within the span of a single day — may help ecologists understand when microscopic animals in the water column choose to feast upon these algae. But knowledge of how the algal species regulates its fat stores could also help humans.

“Algae recently became more familiar to the general populace because of biofuel production,” said Cattolico. “We needed a simple alga for looking at fat production and fat regulation.”

This led Cattolico to team up with , then a graduate student in the 91Ě˝»¨Department of Genome Sciences, to sequence the complete genome of this species. Hovde wanted to work on algae in biofuel production, and Chrysochromulina was ideally suited for the task because, unlike most other haptophytes, it has no protective cell wall.

Hovde and Cattolico uncovered other surprises in the Chrysochromulina genome. Like other algae and plants, Chrysochromulina uses light to make food, through the process of photosynthesis. But they also found another gene, called xanthorhodopsin, that may let the alga harvest light and do work outside of the traditional photosynthesis pathway. Cattolico does not know how the alga uses this gene, but would like to investigate this in the future.

In addition, they identified numerous genes that appear to harbor antibiotic activity, which may be useful as the need for new antibiotics continues to rise. But Chrysochromulina is not universally against bacteria. Through this project, Cattolico and her team discovered that there are at least 10 bacterial species that appear to enjoy living near Chrysochromulina.

“That leads to some interesting questions,” said Cattolico. “Is Chrysochromulina selectively using its antimicrobials? Is it ‘farming’ beneficial bacteria in its neighborhood?”

Cattolico would like to understand how these bacteria affect which genes Chrysochromulina switches on and off. That information may pave the way for new studies of the ecology of haptophytes, which could be critical in the face of a changing global climate.

“Haptophytes are very important to our ocean health, especially with these massive —sometimes toxic — blooms they make,” said Cattolico. “We need to understand this issue because ecosystems are only going to get more compromised with climate change.”

The research was published Sept. 23 in the online, open-access journal PLOS Genetics. First author Hovde is now a postdoctoral researcher at the Los Alamos National Laboratory. Other 91Ě˝»¨co-authors are , Heather Hunsperger, Scott Ryken, Will Yost, Johnathan Patterson and . and were co-authors from Los Alamos National Laboratory, as well as from San Diego State University. The research was funded by the U.S. Department of Energy, Washington Sea Grant, the National Science Foundation, the National Institutes of Health, Los Alamos National Laboratory and the Defense Threat Reduction Agency.

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For more information, contact Cattolico at 206-543-1627 or racat@u.washington.edu.

Grant numbers: U.S. Department of Energy (DE-EE0003046), Sea Grant (NA07OAR-4170007), Los Alamos (WSYN_BIO), Defense Threat Reduction Agency (CBCALL 12-LS6-1-0622), NIH (1RL1CA133831, T32 HG00035), NSF (DGE-0718124, DGE-1256082).

“” comes out Nov. 16 from W.W. Norton & Co. , a 91Ě˝»¨professor of Earth and space sciences, co-wrote the book with his wife, , a biologist and environmental planner. From restoring the soil in their urban yard to building a garden, to grappling with a cancer diagnosis for BiklĂ©, the authors share their discoveries about the unfolding revolution of microbiome science and how it transformed their view of nature — and themselves.

The book recounts the heyday of microbiology that led to germ theory and how, by the late 20th century, scientists changed the tree of life to reflect the dominance of microbial life. It then focuses on the new understanding of microbes now emerging from seemingly unrelated fields such as plant science and immunology. Drawing on this latest work, the authors see stunning similarities between the root of a plant and the human gut that are both profound and fundamental. Beneficial relationships between microbes and their human and plant hosts are unimaginably old and have shaped each through the millennia in ways we are only beginning to understand. The book covers unusually effective new therapeutic approaches based on microbiome science, including fecal transplants for people and probiotics for soils.

Montgomery and Biklé urge cultivating and protecting the microbial allies deep within our gut and beneath our feet to restore the land and heal ourselves. They see a common pathway for doing both — mulching our inner soil with a diet abundant in plant foods and mulching the soils beneath farms and gardens with organic matter and cover crops.

Montgomery is a three-time winner of the Washington State Book Award, for “” in 2013, “” in 2008 and “” in 2004.

Montgomery and BiklĂ©, who will be speaking at , answered questions about their book for 91Ě˝»¨Today:

Q: The book is part history lesson, part science book, part a personal narrative. Where did the idea for the book originate? Did the concept change over time?

A: The book began in the garden, and we remain astonished at where we ended up. Our original intent was to write a hybrid memoir-essay about building our garden, and the need to restore soil globally. One of the first areas we began to research was the effects of adding organic matter to soil, since that was what we had done. Once we dug in, we began to realize that microbes play a foundational role in soil fertility and plant health.

Then the human health dimensions of the microbial world hit us hard in 2011. We were partway through writing the book when Anne was diagnosed with a virus-caused cancer. She has since made a full recovery, but the microbial world was suddenly not so wonderful. While we’d always planned to research and write about food and human health through the lens of soil health, we never imagined that a cancer diagnosis would help us frame the topic.

And as we began putting the story together it was amazing to read things in gastroenterology and immunology journals that were the same concepts we’d encountered in plant science and agronomy journals. At this point, we knew we were onto something bigger, about how important the hidden half of nature is to the health of plants and people.

Q: You wrote the text together, your first time collaborating on a book. What was that like?

A: We get asked this question a lot. As in any endeavor, there are parts that go so well it barely feels like work, and there are parts where you struggle. But the truth is, neither one of us could have written the book without the other. And we think the book is far better because of our collaboration and different expertise. Obviously we know each other very well and our strengths and weaknesses as writers. Most of the time our thinking converged. But we had heated disagreements, too. Early on, however, we adopted a simple rule — we both had to be satisfied, at least minimally, with both the substance and style of the writing that would become part of the final manuscript.

Q: What is the coolest thing you want people to know about microbes?

A: Microbes are integral parts of every organism on this planet. Yet we’ve spent the last century trying to scrub them off our bodies or indiscriminately kill them. So it is quite astounding to now learn that communities of microbes play as significant a role in preventing disease and sickness as in causing them. And the mechanisms that underlie this reality reveal something just as cool: Microbes considerably expand the number of genes within us. There are around 25,000 protein-coding genes that we each inherited from our parents. The bacterial members of our microbiome contribute approximately 2 million more genes. Add approximately 4 million additional genes from the rest or our microbiome — like viruses — and that’s pushing 6 million genes working away in us that we didn’t inherit in the usual fashion.

This is a pretty fundamental insight. It calls into question many common practices in medicine and agriculture — and is guiding the way to new practices that can address some of the most critical problems facing humanity today, from flagging soil fertility to the rising incidence of chronic and autoimmune diseases around the world.

Q: Dave, your previous books have been about large-scale things, like erosion and floods. Does this book reflect a change in your focus as a geologist?

A: I haven’t so much changed my focus as a geologist, but more how I see nature and the soil. Still, I’m not about to try and retool myself into a microbiome researcher. I’m just not that good at or fond of lab work — I became a geologist because I like to be outside. This book greatly enhanced my awareness about the connections between soil fertility and the microbes that mediate those processes. It really opened my eyes to how fast soil carbon and fertility can be restored if one focuses on the health of soil microbes. And that has completely changed how I think about the potential to keep humanity’s relationship to the soil from following the historical pattern of soil degradation that I laid out in my previous book, “Dirt: The Erosion of Civilizations.” In fact, I’m now working on a book for which I’ve been interviewing farmers around the world who have restored depleted soils, and in the process slashed their agrochemical use without any loss in crop yields. “The Hidden Half of Nature” naturally flows into this next book because the soil restoration techniques of these farmers, by and large, involve better stewardship of the soil microbiome.

Q: Do you think this book is part of a broader shift in how people think about and interact with microbes?

A: Given all the discoveries about microbiomes — that seem to grow daily — we certainly think so. It really is time to change our relationship with the microbial world. It’s already begun at some level, if you consider the surge in interest in fermented foods like sauerkraut and yogurt. An unusual medical therapy based on microbiome science — fecal transplants — is more evidence that a shift is underway. And in agriculture, farmers are starting to see the benefits of inoculating their soil with beneficial microbes or growing them in the soil through planting cover crops. We see this shift as part of something much bigger, and try to capture it in the last chapter of the book when we write: “Nature is not out there in some distant and faraway land. She is closer than we ever imagined, right inside of us.”

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For more information, contact Montgomery at 206-685-2560, 206-618-9220 or bigdirt@uw.edu.

A selection of recent news stories from the 91Ě˝»¨Health Sciences and 91Ě˝»¨Medicine:

Cuts to maternal-child services linked to underweight infants

A two-state study demonstrated that cutbacks in maternal-child services led to a higher number of low-birthweight newborns. 91Ě˝»¨School of Nursing researchers  led  explorations of the health effects of budget reductions in maternal-infant programs.  The supposed cost-saving strategy  ends up being uneconomical. The costs for caring for low-birthweight babies are high, both for the health-care system and for families, the researchers said. The long-term, detrimental effects of low birthweight, they added can sometimes last well into adulthood. Read more at HS NewsBeat:

Monumental task: Keeping the U.S. water supply safe.

The cool, clear tap water filling your glass seems like a simple pleasure.  But behind the scene, many individuals, programs, and systems are at work to assure your drinking water is pure.  No one wants a repeat of the contamination that turned off the faucets in parts of West Virginia.  Learn how 91Ě˝»¨environmental health students and faculty are taking steps to protect water supplies locally and nationally.

Get the facts on MERS

As Middle East respiratory syndrome makes another U.S. appearance, this time in Florida, the Centers for Disease Control and Prevention, the American Public Health Association and the World Health Organization ramp up efforts to inform people about the emerging viral infection. See their tips for routine infection control measures.

The details of these findings suggest potential targets for treating HCV, according to a research team led by Dr. Ram Savan, assistant professor of immunology at the 91Ě˝»¨. The study was published in Nature Immunology.

HCV infects more than 150 million of the world’s people. The virus is notorious for evading the body’s immune system and establishing an infection that can continue for decades, despite treatment. A lasting infection can damage the liver, and in some cases produce liver cancer. HCV infection is a major cause of liver failure requiring an organ transplant.

The virus, hiding in other tissues, can return in the transplanted liver. HCV and the human immune system are engaged in a seemingly never-ending duel, each trying to overcome the others latest move. Several HCV mechanisms for defying the body’s immune system have already been uncovered.

Present treatments are about 70 percent effective in curing the infection, Savan said. The triple combination treatments consist of interferon, ribavirin and direct-acting antiviral agents.

He added, however, that resistant strains of HCV are emerging in antiviral treated patients. Also troubling, he said, is that certain patients can undergo almost a year of treatment weeks – and still be infected. They’ve endured the unpleasant, flu-like side effects of the regimen with little benefit.

After observing that patients of Asian descent reacted better to HCV treatment than did those of African descent, other research teams searched entire human genomes to identify gene clusters associated with response to therapy.

On chromosome 19, the scientists found different, single-letter DNA code changes linked to treatment response and the natural ability to clear HCV infection.

These tiny genetic variations are located near an area that encodes for interferon-lamda3 (IFNL3), also called interleukin-28B. Viruses can trigger blood cells and other cells to produce this potent substance, which is released to protect against virus invasion.

The mechanism aligning this genetic finding with clearance of HCV had been elusive, Savan’s group noted in their paper. His team discovered how the single-letter variation in the IFNL3 gene was responsible for the differences between those who could and those who could not effectively clear HCV.

Individuals who carry the T (for thymidine) variant have an unfavorable outcome in fighting HCV, while those who carry the G (for guanosine) variant have a favorable outcome.

Their data showed that HCV could induce liver cells to target the activities of the IFNL3 gene with two microRNAs. MicroRNAs are silencers: They stop the messengers who transmit information to produce a protein from a gene, in this case the production of the antiviral interferon lambda-3.

These two particular microRNAs are generally turned off in liver cells, until HCV coerces them to act on its behalf. Normally, these so called myomiRs are associated with myosin-encoding genes in skeletal and heart muscle.

“This is a previously unknown strategy by which HCV evades the immune system and suggests that these microRNAs could be therapeutic targets for restoring the host antiviral response,” the researchers wrote in their paper. Adding support to this suggestion is the researchers’ observation that the bad-acting microRNAs in question could not land on and repress interferon lambda-3, if the host carried the favorable “G” variant.

In those cases, the host is able to escape adverse regulation by HCV, the researchers observed. Savan pointed out that this particular escape variant has been found only in humans, and not in other primates. He said it is not yet known if the G variant arose in humans as a response to selective pressure by infection with HCV.

Savan came to the 91Ě˝»¨ in late 2011 from the National Institutes of Health. The first author on the paper, Adelle McFarland, was a research scientist in Savan’s lab and is now a graduate student in the Molecular and Cellular Biology Program at the UW.

Funding for this project came from a start-up grant from the 91Ě˝»¨Department of Immunology and from the National Institutes of Health (HHSN261200800001E, AI060389, AI88778, and CA148068)

Other researchers on the project, reported in the article “The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAS,” were Stacy M. Horner, Abigail Jarret, Rochelle C. Joslyn, all at the 91Ě˝»¨Department of Immunology at the time of the study; Eckart Bindewald and Mary Carrington of the Frederick National Laboratory for Cancer Research, Bruce A. Shapiro of the National Cancer Institute, and Don A. Delker and Curt H. Hagedorn, both of the University of Utah. Michael Gale, Jr., a collaborator in this study, is from the 91Ě˝»¨Department of Immunology.

A Nature Immunology News & Views commentary, “Outflanking HCV.” by Zhigang Tian of the University Of Life Sciences Of China in Hefei, gives a perspective on the research findings.