In this week’s issue of Science, a team of researchers from the United States and Sweden report on a newly identified factor that controls the natural input of new nitrogen into boreal forest ecosystems. Nitrogen is the primary nutrient that dictates productivity (and thus carbon consumption) in boreal forests. In pristine boreal ecosystems, most new nitrogen enters the forest through cyanobacteria living on the shoots of feather mosses, which grows in dense cushions on the forest floor. These bacteria convert nitrogen from the atmosphere to a form that can be used by other living organisms, a process referred to as “nitrogen-fixation.” The researchers showed that this natural fertilization process appears to be partially controlled by trees and shrubs that sit above the feather mosses.

In the summer of 2006, the researchers placed small tubes, called resin lysimeters, in the moss layer to catch nitrogen deposited on the feather moss carpets from the above canopy and then monitored nitrogen fixation rates in the mosses. The studies revealed that when high levels of nitrogen were deposited on the moss cushion from above, a condition typical of young forests, nitrogen fixation was extremely low. In older, low-productivity forests, very little nitrogen was deposited on the moss cushion, resulting in extremely high nitrogen fixation rates.

Nitrogen fixation is an energy demanding process. Thus, when mosses are exposed to high concentrations of bioavailable nitrogen, the cyanobacteria will consume this resident nitrogen rather than expending energy on fixing new nitrogen. Thus the nitrogen content of canopy throughfall acts as a regulator of newly fixed nitrogen into these boreal forests. For this same reason, elevated nitrogen deposition from pollution likely reduces moss nitrogen fixation rates. The moss would initially buffer the forest against the effect of nitrogen added as pollution or fertilizer; however, chronic elevated nitrogen inputs would ultimately eliminate this natural source of forest fertility.

The feather moss-cyanobacterial association provides a unique model system in which to study nitrogen feedback mechanisms. The cyanobacteria reside on the leaves, thus the nitrogen status of the canopy throughfall directly influences nitrogen fixation in the feather mosses. This direct expression of a nutrient feedback mechanism could not be detected in other nitrogen fixing plant species, such as legumes, that house their nitrogen fixing bacteria below ground and where soils and decomposing litter intercept and modify the nitrogen from throughfall before it reaches the bacteria.

These findings are important from a global standpoint, because feather mosses (and associated cyanobacteria) are the primary source of biologically fixed nitrogen in the boreal forest biome. The dominating feathermoss Pleurozium schreberi is also found in arctic and temperate biomes and thus may be the widest distributed individual nitrogen-fixing plant species on Earth. Understanding feed back mechanisms among dominating organisms that regulate fundamental ecosystem processes are integral to our ability to predict long term outcomes of global carbon dynamics.

The two studies in the May 30th issue of Cell, a Cell Press publication, uncover the crystal structure and biochemical activity of an enzyme known as XPD helicase taken from Sulfolobus archaea, microbes distinct from bacteria that share many fundamental genes with humans. For reasons that had remained rather mysterious until now, point mutations in human XPD sometimes at neighboring sites can spell the difference between cancer-prone xeroderma pigmentosa, the aging disorder known as Cockayne syndrome and another aging disorder called trichothiodystrophy.

If you consider the linear sequence of XPD and map the [disease-linked] point mutations onto it, there is nothing clear about why they would be causative for one of the three diseases or another, said Jill Fuss of The Scripps Research Institute. By having these structures for XPD, we suddenly see how it is working.

The protein from archaea is a simplified model, but that doesn’t stop us learning a lot about the biology of the human enzyme, said Malcolm White of University of St Andrews, who led the other study. Archaeal protein structures are often very close matches to the equivalent proteins from humans, even though they diverged from one another three billion years ago. We can learn a lot about human health by looking deep into evolutionary time.

Archaea have particular similarities with humans and other eukaryotes in the way in which they process information, including DNA replication, transcription and repair, White explained. One of those common elements is XPD helicase, a component of a fundamental complex (known as TFIIH) with roles in initiating the transcription of genes into the templates for protein and in the repair of damaged DNA. In both instances, the helicase parts the two DNA strands at either the transcription start site or the site of DNA damage.

Defects in XPD are known to underlie xeroderma pigmentosa (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). Although people with all three diseases share a sensitivity to the sun, they differ greatly in their predispositions to cancer or accelerated aging, explained John Tainer, who led the Scripps study. XP patients show several 1000-fold increase in skin cancer, whereas neither CS nor TTD patients show an increase in the cancer incidence despite their sun sensitivity. Furthermore, both CS and TTD are premature aging diseases plus developmental disorders, with CS patients being more severely affected and exhibiting severe mental retardation from birth.

Both teams now have evidence to explain what separates the diseases despite their similar molecular causes. They find that XP-causing mutations in XPD all fall in sites where the helicase binds ATP (the energy currency of the cell) or DNA. Those alterations leave the enzyme unable to function in DNA repair. However, the overall effect on the structure of the enzyme is minimal. As such, the enzyme still fills its position in the TFIIH complex, allowing transcription to proceed. That inability to repair defects, leaves those with XP prone to developing cancer as mutations arise and go uncorrected.

In the case of TTD, the defect is quite different, White said. TTD-linked mutations are found all over the protein at points important to its interactions with other proteins. Therefore, those mutations leave the protein floppy, destabilizing the entire TFIIH complex and causing defects in both transcription and repair.

It is thought that the transcription defects protect against cancer, but lead to an increase in cell death and therefore the rapid aging symptoms seen in TTD patients, White said.

As for CS, Tainer’s group suggests it results when defects in XPD lock the protein into a rigid position. As a result, they said, the protein may stick in repair mode and cut out DNA at sites where it should be transcribing.

White agrees that CS seems to result from mutations that influence the XPD protein’s flexibility. However, he’s not yet sure exactly how that leads to the symptoms of CS.The new insights into XPD point to the importance of whole proteins, not just their active sites.

“We’ve been able to characterize three activities together with the structure”, Tainer said. “We’ve shown how mutations in the binding site alone can cause cancer. Scientists often thought it was just the active sites that were important that other changes wouldn’t matter. But we see that other changes can lead to very severe defects.”

The results also hold an important general lesson for the value of protein structure for understanding gene function. The results of the Human Genome Project have revealed associations between sequence mutations and particular diseases or disease risks, but in many cases we don’t know why, Tainer said. As in the case of XPD, the protein structures may hold the key.

US researchers have created ‘living computers’ by genetically altering bacteria. The findings of the research, published in BioMed Central’s open access Journal of Biological Engineering, demonstrate that computing in living cells is feasible, opening the door to a number of applications including data storage and as a tool for manipulating genes for genetic engineering.

A research team from the biology and the mathematics departments of Davidson College, North Carolina and Missouri Western State University, Missouri, USA added genes to Escherichia coli bacteria, creating bacterial computers able to solve a classic mathematical puzzle, known as the burnt pancake problem.

The burnt pancake problem involves a stack of pancakes of different sizes, each of which has a golden and a burnt side. The aim is to sort the stack so the largest pancake is on the bottom and all pancakes are golden side up. Each flip reverses the order and the orientation (i.e. which side of the pancake is facing up) of one or several consecutive pancakes. The aim is to stack them properly in the fewest number of flips.

In this experiment, the researchers used fragments of DNA as the pancakes. They added genes from a different type of bacterium to enable the E. coli to flip the DNA ‘pancakes’. They also included a gene that made the bacteria resistant to an antibiotic, but only when the DNA fragments had been flipped into the correct order. The time required to reach the mathematical solution in the bugs reflects the minimum number of flips needed to solve the burnt pancake problem.

“The system offers several potential advantages over conventional computers” says lead researcher, Karmella Haynes. “A single flask can hold billions of bacteria, each of which could potentially contain several copies of the DNA used for computing. These ‘bacterial computers’ could act in parallel with each other, meaning that solutions could potentially be reached quicker than with conventional computers, using less space and at a lower cost.” In addition to parallelism, bacterial computing also has the potential to utilize repair mechanisms and, of course, can evolve after repeated use.

Life in outer space is an absolute certainty, and it is likely to be more familiar than we might think, according to an article in the May issue of Microbiology Today. Ever since the start of the space race we have sent more than just satellites and astronauts into space: spacecraft are not routinely decontaminated and are teeming with microbial life.

“Wherever man boldly goes his microbial fauna is sure to follow,” said Lewis Dartnell, an astrobiologist at University College London. The Russian space station Mir was launched in 1986 and microbial studies investigated the diversity of bacteria living alongside the astronauts. In 1998, free-floating blobs of water found during a NASA mission to the station were analyzed and discovered to contain microbes including faecal bacteria like E. coli, plague bacterium-related species of Yersinia, and even what was suspected to be Legionella, as well as fungi, amoebae and protozoa.

“Preventing the spread of microbial life between worlds of the solar system has been a top priority for decades now,” said Lewis. “This effort is known as planetary protection.” Today’s International Space Station (ISS) is much cleaner than Mir was 20 years ago, thanks to HEPA filters, weekly cleaning and biweekly disinfecting regimes. But inevitably, the ISS is still far from being bug-free; recent sampling revealed the bacterium Staphylococcus epidermidis surviving in different areas.

But it’s not just planets we need to protect – astronauts are at increased risk of infection in space. Respiratory infections are common among astronauts and diseases occur in a quarter of space shuttle flights. “Prolonged exposure to cosmic radiation and microgravity is believed to have a negative effect on the immune system, and disease transmission is enhanced within the closed environment of recycled air and water,” said Lewis Dartnell. Microbes also pose an increased risk of allergies, toxic air and water supply and even biodegradation of critical spacecraft components.

This week, the Phoenix lander touched down on Mars, hoping to take the first ever direct measurements of Martian water and organic molecules. “To guarantee the cleanliness of the robotic arm, it was enclosed in a biobarrier bag – effectively an interplanetary condom,” said Lewis. But this will not be a feasible control measure for humans. “Humans and spaceships are inherently dirty and once we arrive to plant flags in the rusty soil our microbial entourage will begin leaking out onto Mars.” What’s more, microbes have an uncanny ability to survive as spores, resistant to heat, cold and radiation. “Once humans have visited Mars, we may never be certain that any biological discoveries weren’t simply signs of our own dirty sleeves,” said Lewis Dartnell.

In fact, we might actually need to take microbes on a manned mission to Mars. “For longer missions, it will not be possible to take sufficient supplies from Earth,” said Lewis. “Scientists are developing ingenious life support systems relying on plants and micro-organisms to provide food, waste recycling and water purification.” Of course, in this case, an outbreak of harmful microbes could crash life support systems as well as affecting the health of the crew, endangering the whole mission. “For better or worse, space bugs are here to stay.”

Ships are inadvertently carrying trillions of stowaways in the water held in their ballast tanks. When the water is pumped out, invasive species could be released into new environments. Disease-causing microbes could also be released, posing a risk to public health, according to an article in the May issue of Microbiology Today.

“There is no romantic adventure or skullduggery at work here,” said Professor Fred Dobbs from Old Dominion University, Virginia, USA. Ships pump water in and out of ballast tanks to adjust the waterline and compensate for cargo loading, making the ship run as efficiently as possible. These tanks can hold thousands of tonnes of water. “Any organisms in the water are likely to be released when it is next pumped out.”

Many non-native animals and plants have been taken to new environments and become invasive, threatening the survival of local species; some fundamentally alter the ecosystem. Zebra mussels were introduced in North America and the comb jelly in the Black Sea and both have had enormous ecological and economic impacts

For more than 20 years we have known that a variety of large phytoplankton and protozoa are transported in this way, but we know very little about smaller microbes like bacteria and viruses. “It is inevitable that hundreds of trillions of micro-organisms enter a single ship’s ballast tank during normal operations,” said Professor Dobbs. The majority of these microbes are harmless, but some are a potential risk to public health.

“Vibrio cholerae, which causes cholera in humans, can be carried in ballast tanks,” said Professor Dobbs. “There have been no known outbreaks of disease associated with ballasting activities, but the water is only sampled very rarely.” Other disease-causing microbes in the tanks include Cryptosporidium parvum and Giardia duodenalis, which cause stomach upsets.

Some people say microbes are present everywhere; they may be easily dispersed because they are so small. However, many experts believe micro-organisms have a “biogeography”, a natural home, which means they could become invasive if moved and have a negative effect on different environments. There is some evidence for this argument: two phytoplankton species called diatoms were introduced to the English Channel from the North Pacific Ocean

The International Maritime Organisation, which sets rules and standards for the global shipping industry, has proposed an upper limit to the numbers of Vibrio cholerae, E. coli, and intestinal enterococci contained in discharged ballast water. A few ships are also using different treatments to reduce and even eliminate the microbes in their ballast water. “A number of techniques are being looked at for this purpose, from filtration to biocides, ultrasound to ultraviolet irradiation,” said Professor Dobbs. “Our understanding of the issues involved will increase as more studies are carried out, particularly those employing the tools of modern molecular biology.”

Researchers from the John Innes Centre and the University of East Anglia have recently elucidated the structure and function of an enzyme which is involved in decorating antibiotics with sugar molecules. Many antibiotics have a variety of different carbohydrate molecules attached to them which can help the antibiotic to be taken up by the target organism or overcome resistance. By manipulating the sugar, it may be possible to restore usefulness in antibiotics to which resistance has developed.

The aim of this research was to find out how these sugars are made, and how their structures affect their biological activity. The researchers studied an enzyme from a little studied species of Streptomyces bacteria, which produces the antibiotic tylosin. The enzyme they looked at is involved in making a sugar molecule that decorates tylosin. By working out how the carbohydrates are made, it may be possible to make unnatural sugars, with different properties.

“This is a bit of biochemistry we can’t do with chemistry. We need to go back to the fundamentals of how these sugars are put together in nature”, said Professor Rob Field. “We want to see what happens when we decorate an antibiotic with sugar and which sugars make the best decoration.”

They are not yet near to a market product, but trying to understand at a fundamental level how these sugars are made. “We are still putting the toolkit together” said Professor Field. By modelling the enzyme, and comparing it with related enzymes, they have been able to identify the key parts needed for its function, and propose the biochemical basis for how it creates the carbohydrate’s precise st

Once considered a barren plain with the odd hydrothermal vent, the seafloor appears to be teeming with microbial life, according to a paper being published May 29 in Nature.

“A 60,000 kilometer seam of basalt is exposed along the mid-ocean ridge spreading system, representing potentially the largest surface area for microbes to colonize on Earth,” said USC geomicrobiologist Katrina Edwards, the study’s corresponding author.

While seafloor microbes have been detected before, this is the first time they have been quantified.  Using genetic analysis, Edwards and colleagues found thousands of times more bacteria on the seafloor than in the water above.

Surprised by the abundance, the scientists tested another Pacific site and arrived at consistent results.  This makes it likely that rich microbial life extends across the ocean floor, Edwards said.

The scientists also found higher microbial diversity on the rocks compared with other vibrant systems, such as those found at hydrothermal vents.

Even compared with the microbial diversity of farm soil—viewed by many as the richest—diversity on the basalt is statistically equivalent.

“These scientists used modern molecular methods to quantify the diversity of microbes in remote deep-sea environments,” said David L. Garrison, director of the National Science Foundation’s biological oceanography program.

“As a result, we now know that there are many more such microbes than anyone had guessed,” he added.

These findings raise the question of where these bacteria find their energy.

“We scratched our heads about what was supporting this high level of growth when the organic carbon content is pretty darn low,” Edwards recalled.

With evidence that the oceanic crust supports more bacteria compared with overlying water, the scientists hypothesized that reactions with the rocks themselves might offer fuel for life.

Back in the lab, they calculated how much biomass could theoretically be supported by chemical reactions with the basalt.  They then compared this figure to the actual biomass measured.  “It was completely consistent,” Edwards said.

This lends support to the idea that bacteria survive on energy from the crust, a process that could affect our knowledge about the deep-sea carbon cycle and even evolution.

For example, many scientists believe that shallow water, not deep water, cradled the planet’s first life.  They reason that the dark carbon-poor depths appear to offer little energy, and rich environments like hydrothermal vents are relatively sparse.

But the newfound abundance of seafloor microbes makes it theoretically possible that early life thrived—and maybe even began—on the seafloor.

“Some might even favor the deep ocean for the emergence of life since it was a bastion of stability compared with the surface, which was constantly being blasted by comets and other objects,” Edwards suggested.

Still, current knowledge of the deep biosphere can fit on the head of a pin, Edwards said.  Most seafloor bacteria uncovered in this study show little relation to those cultivated in labs, which makes experimentation difficult.

Rather than bringing bacteria to the lab, however, Edwards plans to bring the lab to bacteria—with a microbial observatory 15,000 feet below sea level.

Thanks to a $3.9-million grant awarded in March by the Gordon and Betty Moore Foundation, Edwards and over 30 colleagues will continue studying seafloor bacteria, but will also study their subseafloor cousins that cycle through the porous rock.

The first expedition of its kind, the drilling operation will penetrate 100 meters of sediments and 500 meters of bedrock.

Besides experiments aimed at learning how precisely these bacteria alter rock, the scientists will measure the diversity, abundance and relatedness of microbes at different depths.

This will shed light on whether the bacteria evolved from ancestors that floated down from above or from some as yet unknown source deep in the crust.

The Nature study provides a crucial base of comparison between the seafloor and subseafloor microbes, both completely unknown until just recently.

The decade-long undertaking will further bridge the earth and life sciences, a key goal in the emerging field of geobiology, described by Edwards as the co-evolution of Earth and life.

The deep biosphere is uniquely suited for a geobiological approach, Edwards said, since a proper understanding requires genomics, analysis of microbe-rock chemical interactions and a timescale in the millions of years.

Edwards joined USC two years ago as part of its cluster hire of scientists with multidisciplinary interests related to geobiology.  With its concentration of faculty in the field, Southern California and USC in particular are regarded as hubs for the geobiology research community.

USC recently hosted the 5th Annual Geobiology Symposium, co-organized by USC post-doctoral student Beth Orcutt, the second author of the Nature paper.

In addition, the USC Wrigley Institute for Environmental Studies runs a summer geobiology course on Catalina Island that brings together top students and faculty.

Edwards believes that most people just don’t realize how much life thrives in the watery depths.

“If we can really nail down what’s going on, then there are significant implications,” she said.  “It is my hope that people turn their heads and notice that there’s life down there.”

Scientists search for drug candidates in some very unlikely places. Not only do they churn out synthetic compounds in industrial-scale laboratories, but they also scour coral reefs and scrape tree bark in the hope of stumbling upon an unsuspecting molecule that just might turn into next year’s big block buster. But one region that scientists have not been searching is their guts. Literally.Now, a team of researchers at Harvard Medical School, Brigham and Women’s Hospital, and the California Institute of Technology have demonstrated that a molecule produced by bacteria in the gut’s intestinal microflora can eliminate symptoms of inflammatory bowel disease (IBD), a condition that includes Crohn’s disease and ulcerative colitis, in animal models.

“Given the sheer number of bacteria in the gut, the potential for discovering new molecules that can treat a whole range of these diseases is promising,” says Dennis Kasper, co-lead author on the study, professor of medicine and microbiology and molecular genetics at Harvard Medical School, and director of the Channing Laboratory at Brigham and Women’s Hospital.

The study will appear as the cover story in the May 29 issue of Nature.

Scientists have known for many decades that the mammalian gut is an ecosystem teeming with approximately 1,000 different species of bacteria, species as distinct from the host as a single-cell amoeba in pond scum. Rather than causing disease, these bacteria are responsible for protecting against infection and aiding digestion. An increasing number of scientists also suspect that recent increases in asthma and even certain food allergies are caused by disruptions in the delicate balance of this intestinal ecosystem.

In 2005, Kasper and Sarkis Mazmanian, then a postdoc in Kasper’s lab and now an assistant professor of biology at the California Institute of Technology, discovered that a species of intestinal bacteria called Bacteroides fragilis could restore immune system balance in mice that were bred to lack intestinal bacteria. A particular product of B. fragilis, a sugar molecule called polysaccharide A (PSA), recovered the equilibrium of a certain subclass of immune system cells (called Th1 and Th2) whose levels became skewed when bacteria in the gut were absent. The researchers referred to PSA as a “symbiosis factor,” one that established a beneficial link between bacteria and mammals. This was the first study in which such a link was demonstrated.

Interestingly, when the study was completed, Kasper and Mazmanian found in these mice an abundance of immune system cells that were known to protect against colitis and Crohn’s disease. In the current report, the groups decided to expand these findings and explore potential links between PSA and inflammatory bowel disease.

When immunocompromised mice with a specific pathogen-free microbiota were given an intestinal bacterium called Helicobacter hepaticus, they soon developed “rip roaring” IBD, according to Kasper. However, when Helicobacter was combined with B. fragilis, the mice were fine. Further experiments revealed that PSA—the special sugar molecule—was the key factor in preventing IBD. In fact, when mice were given Helicobacter combined with PSA purified from B. fragilis bacteria, they showed no symptoms of IBD.

“But then the key question was, if PSA was essential for preventing these animals from coming down with either colitis or Crohn’s, how did it do it”” says Kasper. “What was the mechanism””

The answer came by studying a subset of interleukins, that is, molecules secreted by immune cells.

Previous studies had shown that two particular interleukins, called IL-17 and IL-23, promote intestinal inflammation and are present at high levels in IBD patients. Here, while the researchers found IL-17 and IL-23 in the guts of animals who had received Heliobacter alone, these interleukins were absent from animals who had also received both PSA-producing B. fragilis and purified PSA.

“We realized that something in PSA must be preventing the inflammation that causes colitis and Crohn’s, which would explain the reduction in IL-17 and IL-23,” says Kasper.

This hunch brought the researchers to consider a third interleukin, IL-10. The opposite of IL-17 and IL-23, IL-10 is anti-inflammatory and had previously been shown to protect against experimental colitis.

The researchers once again administered Helicobacter and PSA-active B. fragilis (the combination that had previously led to healthy mice), only this time they included an antibody that blocked IL-10. As a result, the mice all came down with IBD.

“This demonstrated for us the mechanism by which PSA protects against IBD,” says Kasper.

Indeed, the researchers deduced that PSA prompts immune system cells to secrete IL-10, which in turn suppresses the inflammation caused by IBD. In other words, PSA is an anti-inflammatory.

This research should encourage people (including many scientists) to consider the vast potential for beneficial contributions to human health by “good” bacteria. And what’s more, “This is the first time that a beneficial molecule produced by intestinal bacteria has been shown to work therapeutically in an animal model,” says Mazmanian.

The researchers caution that these findings do not promise any near-term treatments for IBD. “PSA might do the same thing in humans, and it might not,” says Kasper.

However, the mechanism that they’ve discovered should persuade scientists and drug manufacturers to consider new sources for expanding the drug pipeline.

“There is currently no effort to develop molecules that are naturally made by bacteria to use therapeutically,” continues Mazmanian. “This study opens up that possibility.”

Full citation:
Nature, May 29, 2008, 453 (7195), 620-624
“A microbial symbiosis factor prevents intestinal inflammatory disease”
Sarkis K. Mazmanian(1), June L. Round(1) & Dennis L. Kasper(2,3)

A group of Duke University researchers have made a major advance in understanding how bacteria divide.  These results could lead to new antibiotic treatments that prevent dangerous bacteria from multiplying.

Normally, bacteria divide by forming a ring that pinches the cell in two.  The ring is called a “Z ring” after the protein FtsZ, which forms a ring-shaped scaffold and then squeezes it smaller.  In bacteria, the Z ring also contains a dozen other proteins, all believed to be essential for division.

The Z ring normally pulls in on the cell membrane by binding to another protein, FtsA, which has one end attached to the inner cell membrane and the other end connected to FtsZ.  When the Z ring constricts, it completely pulls in the membrane and nips the bacterium in two.

But cell biology research scientist Masaki Osawa, Ph.D., cut FtsA out of the system by making an FtsZ that could bind directly to the membrane, and called it “membrane targeted FtsZ” or FtsZ-mts.

First, Osawa demonstrated that the new protein, FtsZ-mts, assembled Z rings in bacteria.

Then he constructed a greatly simplified cell-division machine in microscopic oil droplets, called liposomes, that demonstrated the important role of FtsZ in the division process.  He was able to assemble Z rings in this completely artificial system, the liposome, a tiny hollow sphere of fat that mimics natural cell membranes.

To do this, Osawa mixed the liposomes with FtsZ and GTP, a molecule that provides energy.  On a microscope slide the liposomes fused and stretched into tubes that mimicked the shape of E. coli and other rod-shaped bacteria.

“It was a happy coincidence that the size and shape of the liposomes was similar to that of rod-shaped bacteria,” says co-author Harold Erickson, professor of cell biology.  “These tubular liposomes are a new micro-structure, and their formation is still a mystery.”

During the experiment, fluorescently labeled FtsZ-mts was initially on the outside of the liposomes, but some of the tubular liposomes ended up with FtsZ on the inside.  “We don’t know how this happens, but it is a key to the discovery,” Osawa said.

Inside the liposome the FtsZ formed multiple closed rings that aligned perpendicular to the length of the tube, just as Z rings form in bacteria.  They also slid back and forth, and where they collided, they stayed together and formed brighter Z rings.  And as the Z rings grew in brightness, they visibly pulled the wall of the liposome inward.

“The Z rings are clearly generating force and causing the constriction,” Osawa said.  A movie the team made shows several constrictions in the wall occurring at the sites of the bright Z rings.  When the GTP in the liposome is used up, the tube eases out of its constrictions into its original shape.

“We believe our simple system may recreate the mechanism that the earliest bacteria used to divide.  They probably had FtsZ alone,” Erickson said.  “Osawa’s experiments show that FtsZ, a membrane tether, and the inside surface of a tubular membrane are all that’s needed to assemble the Z ring and generate a constriction force.”

The artificial Z rings were not sufficient to pinch the liposomes in half, “probably because their walls are much thicker than the membrane of a bacterium,” Osawa noted.  “We are now working to make thinner liposomes, so that we can achieve complete division.”

Erickson said that FtsZ is the bacterial ancestor of tubulin, the protein that makes the microtubules in animal cells and is the target of a number of anti-cancer drugs like taxol.  Although FtsZ is not sensitive to taxol, anything learned about the bacterial ancestor will help us understand microtubules, which help animal cells to keep their shape and control their movements, he explained.