Tag Archives: microbes

Open seminars: a new and good idea

One of the things I liked best about being an academic researcher was group meeting. Every week, a different student or scholar would present some fresh data from their own projects. And these meetings were casual and interactive: you could interrupt any time with questions.

In industry chances to keep up with fundamental discovery science outside of your own core area can be more limited. Folks (mainly job candidates) do visit the corporate world to give research talks, and of course industrial scientists still attend conferences, but those interactions — while invaluable — aren’t as informal. The work presented is always well-polished, and people usually shy away from long technical questions and discussion.

That isn’t the case with MicroSeminar: it’s a new(ish) online-only, publicly accessible research seminar in microbiology created by Jennifer Biddle and Cameron Trash. Once a month or so, people from all over the world log into a Google Plus hangout, or watch YouTube — live or when you get free time — as some of the new fresh hot research in environmental microbiology, microbial ecology, and biogeochemistry gets presented. The feel is informal, with lots of Q&A, and you don’t even have to leave home (or bed!). Here are some of the talks I’ve enjoyed so far.

And don’t just take my word for it. Here are some similar thoughts from Pat Schloss:

The cost of going to ISME [a conference] in Korea this summer? In the thousands. Cost of sitting with your laptop watching a seminar? Zilch. Jennifer is correct that this won’t kill conferences. Conferences have a huge social aspect and provide great opportunities for networking. But the science is frequently stale and pulled from the pages of last year’s AEM [a journal]. I think there’s great potential with this model to change how we disseminate information to our colleagues. Like I said, I think this is big, deserving of your attention and perhaps others will create parallel online seminar series that are either more specialized or more general.

And if microbiology isn’t your cup of tea? If you’re an academic in a different field? Like Pat says, maybe you should start another online seminar program like this one.

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Learning to listen to the silent majority

the-silent-majority
Image from here.

Ninety-nine percent. That is the fraction of microbes that aren’t cultivatable by microbiologists. Throughout Earth’s ecosystems, they are there, living, breathing, metabolizing…but because microbiologists can’t grow them in their labs, figuring out what this “silent majority” of microbes do has been tough.

But new lots of new research is changing that. First, microbiologists have been cooking up (literally!) new ways to grow microbes. The old recipes for growth medium turned out to be toxic for many species of bacteria. Second, in many cases, it’s turned out that cultivation is possible, with sufficient time and attention to detail. (Breaking out the microscope is almost never a bad idea.)

Lastly and most impressively, a team has demonstrably slashed the fraction of “uncultivatable” microbes from 99% to something more like 50%…by cultivating the bacteria. Their approach to this impressive success relies on a microfluidic cultivation device they call iChip. These chips are made of hydrophobic plastic arrayed with holes about 1 μL in volume. The holes are open on both top and bottom. To use it, the chip is immersed in a suspension of microbes from environmental samples, so each hole fills up with (on average) about one cell from the sample. Each side of the chip is then sealed with permeable membrane filter. The filter has pore sizes big enough to let soluble nutrients in, but small enough to block microbial cells from leaving (0.03 μm filters seems to do the trick).

Next comes the key step. The sealed chip is returned to the environment from which the sample came for several weeks — the waiting game begins. In their latest study, the team looked at soil bacteria from a grassy field in Maine, so they buried their seeded chip back into Maine soil and left there for a whole month.

New colonies of microbes, unrelated to anything previously cultivated in a lab, grow in many of iChip’s wells. In 2010, the team found an uncultured variant of the marine bacterium Maribacter polysiphoniae that would grew on the chips, but only in proximity to another bacterium they isolated, Micrococcus luteus strain KLE1011. The were able to work out the reason for the co-dependence: M. polysiphonae needed iron-binding siderophores produced by M. polysiphonae to live. In the study published today by Nature, they found a new betaproteobacterium that they called Eleftheria terrae. This bacterium turned out to be tremendously exciting because it produced a new antibiotic, as detailed very well in an accompanying News & Views article.

The chip-based cultivation is clearly useful in understanding what that supposedly “uncultivable” 99% is doing. It’s fun to speculate as to why. It could simply be that microbiologists, a patient lot by most human standards, don’t usually wait long enough for colonies to grow. (One month is a long time!). In some cases, the chip’s holes are small enough so that neighboring cells can still influence growth, such as by supplying those key siderophores. Another possibility is that isolates survive their initial seeding in the chip because it’s an environment they’re accustomed to, but over time as the microcolony grows, they adjust — either through mutation or through somatic adaptation — to life in monoculture. Or it could something else entirely, and oh yes, the answer probably varies from species to species.

Regardless, I expect to be hearing many more reports on cultivating the many “uncultivable” microbes on Earth. As many have previously observed, if we listen correctly, we should indeed be able to hear the microbial silent majority, even as they grow in our labs.

Molecule of note: 3-formyltyrosine

I wish I had a nickel every time I hear that the “metabolome” — the collection of all of the small molecules which exist as intermediaries in the biochemical machinery of living cells — consists of only a few hundred metabolites.  “The number of known metabolites present in many organisms (e.g., yeast) is 10- to 100-fold fewer than the number of genes or proteins,” said one paper, which later went on to say that the yeast metabolome was around 600 metabolites.  Another says that the erstwhile laboratory favorite, the bacterium Escherichia coli, has “694 metabolites present in the in silico metabolome.”

The key words are “known” and “in silico”.  Of course if you limit yourself to what you know about, or limit yourself to “in silico” databases of metabolites that other people know about, you won’t find anything new.  But that doesn’t mean that we know what all of the metabolites are!

Leah C. Blasiak and Jon Clardy provide an excellent counterexample to the idea that we have a handle on the chemical diversity of microbes in a recent paper in the Journal of the American Chemical Society, which details their discovery of 3-formyltyrosine and related metabolites in a marine bacterium.  Drs. Blasiak and Clardy went searching through genomic databases for genes that seemed to encode proteins similar to a newly discovered class of rather funky enzymes, the “ATP-grasp-type ligases”. They found an interesting set of genes from Pseudoalteromonas tunicata, a seabound bacterium which is often found on the surface of seaweed, floating debris, and intervetebrates. They moved those genes to E. coli cells, and then looked in cellular extracts for blips in their mass spectra that did not show up in E. coli cells. They found a few, and after extensive chemical characterization of those blips, they were ready to announce to the world that 3-formyltyrosine was a biologically produced metabolite.

It wasn’t in anyone’s database and hasn’t yet appeared in an in silico metabolome yet, to my knowledge, despite it having been in the Pseudoalteromonas tunicata metabolome for hundreds (at least) of years. How many more metabolites like 3-formyltyrosine are there waiting to be discovered? My money says, “more than a lot of people think.”

A billion years of sulfidic oceans

In last week’s PNAS, A.H. Knoll and colleagues lay out the controlling feedbacks that they think buffered the Earth’s atmosphere at a low-oxygen state for about a billion years. Very interesting reading for anyone into paleoclimatology, paleooceanography, and/or biogeochemistry in general.

Swine flu: a purebred after all?

Contrary to initial reports, some experts think that swine flu may be purely of swine origins. Thanks to revere for the pointer.

Blood Falls

Jill Mikucki’s work on the geobiology of Blood Falls was published in Science last week, and since then, her article has received attention from the lay press as well. And rightly so, I think, because her work is fascinating stuff. A bacterial community thrives in a salty, iron-rich, anaerobic, ice-cold subglacial lake that is apparently completely isolated from Earth’s atmosphere! Waters in the lake do occasionally reach the surface through poorly understood subglacial fluid flows, and when they do, the iron-rich waters rapidly oxidize on exposure to air, forming blood-red mineral deposits. This outflow thus provides at least two things to this ecosystem: a cool name — Blood Falls — as well as a means for Mikucki to sample the otherwise inaccessible, isolated subglacial waters.

I am no chemical oceanographer, but if I understand her paper correctly, she and her co-workers are saying that the sulfate in the subglacial lake catalytically mediates the microbial reduction of triply-charged iron ions to doubly-charged iron ions.  Mikucki and her co-workers think that the sulfate is reduced to sulfite or other intermediate-oxidation-state sulfur compounds, after which it gets re-oxidized back to sulfate, by transferring its newly acquired electrons to triply charged iron.  This recycle keeps sulfate levels in the ecosystem constant, and its a very new idea; usually in anaerobic ecosystems, sulfate reduction goes all the way to hydrogen sulfide; sulfate is not regenerated.

The take-away is not just that life exists down there underneath the glaciers.  The discovery of an extant, non-sulfidic, iron-rich microbial ecosystem based on sulfate cycling lends support to the idea that such conditions may have prevailed during Earth’s past, especially during proposed (and still controversial) Snowball Earth scenarios.

The big remaining question is, what’s the electron donor to the ecosystem?  Mikucki’s earlier articles on the Blood Falls site contain some possible clues. First, the most prevalent microbes at the site are very closely related to Thiomicrospira arctica, a known CO2-eating “autotroph”. So it is likely that not all of the reducing power feeding this ecosystem is in the form of organic carbon. Dissolved organic carbon would be eventually be depleted anyway, if, as is believed, no new sources of DOC have ever fed in fresh carbon to the subglacial lake. Reduced sulfur compounds might be electron donors, but sulfides seemed impossible to detect in the Blood Falls waters. Karsten Pedersen and others have proposed that hydrogen gas drives a microbial ecosystem in the pore waters of hot subterranean granitic rocks. Perhaps hydrogen may turn out to be important in cold subglacial lakes too.

Naturally competent

Ichiro Matsumura of Emory University gave the latest Synthetic Biology Working Group / SynBERC distinguished lecture at MIT yesterday; I was glad to hear his talk. He discussed some of his recent papers, but what jumped out at me most was his call for synthetic biologists to adopt Acinetobacter baylyli ADP1, a gram-negative soil gammaproteobacterium, as a uniquely powerful “chassis” for synthetic biology.

This bug is naturally competent: you can (apparently) just drop in some double-stranded DNA into a log-phase culture, and ADP1 takes it up and treats it as its own. ADP1 also does recombination, so if you design your double-stranded DNA properly, it is easy to get your DNA to insert into the ADP chromosome.

Prof. Matsumura’s lab has also developed a “universal” plasmid. Without species-specific modifications or tuning, it can drive protein expression in a slew of widely divergent bacteria, from Acinetobacter, to E. coli, Bacillus, and more.

Add these two things together, and we are getting closer to a laboratory system for manipulating DNA which does not depend on restriction enzymes or ligases, and in which it is effortless to try out constructs in many different species, not just yeast or E. coli. Yes! Sign me up! A few other workers have developed similar systems before (for example, Daniel Court’s “recombineering” platform) but, at least on paper, the Acinetobacter system looks to be quite a bit simpler and more robust. If you are hungry for more details, check out Prof. Matsumura’s recent conference abstracts.