Slashdot Mirror
New Science Of Metagenomics to Transform Modern Microbiology?
ScienceDaily has a look at the emerging field of metagenomics that watches the DNA of whole communities of microbes to better understand the microbial world. "Metagenomics studies begin by extracting DNA from all the microbes living in a particular environmental sample; there could be thousands or even millions of organisms in one sample. The extracted genetic material consists of millions of random fragments of DNA that can be cloned into a form capable of being maintained in laboratory bacteria. These bacteria are used to create a "library" that includes the genomes of all the microbes found in a habitat, the natural environment of the organisms. Although the genomes are fragmented, new DNA sequencing technology and more powerful computers are allowing scientists to begin making sense of these metagenomic jigsaw puzzles. They can examine gene sequences from thousands of previously unknown microorganisms, or induce the bacteria to express proteins that are screened for capabilities such as vitamin production or antibiotic resistance."
extract dna from millions of microbes?
I always thought that DNA extraction was a manual process... or at least it required a significant amount of manpower to get.
Sometimes the best solution is to stop wasting time looking for an easy solution.
Sounds like this would be just the sort of thing to test out potential DNA snippits before we insert them into our GM foods. I'm all for more GM foods, but I wouldn't say no to a better method of testing. If we could raise large colonies of bacteria with the candidate DNA snippit and 'control' groups without the snippits, we could then use Metagenomics to track protien expressions in the GM colonies and watch for unwanted expressions as well by comparing them with the data gathered from the control colonies. Granted, it's a jump from using the DNA in bacteria to the plants and food themselves, but such a technique could be useful in refining the targeted DNA.
Demented But Determined.
It would be nice to see if they can do this within a small, confined area, like onboard a small underwater craft to study microorganisms that would otherwise die if removed from the depth. There's bound to be a lot of weird stuff down there that can't currently be studied.
...which is why you're still having trouble. The article is in fact about new developments that allow this sort of thing, which as your belief would indicate, has not been possible so far. Check out this paragraph from TFA.
"Although the genomes are fragmented, new DNA sequencing technology and more powerful computers are allowing scientists to begin making sense of these metagenomic jigsaw puzzles. They can examine gene sequences from thousands of previously unknown microorganisms, or induce the bacteria to express proteins that are screened for capabilities such as vitamin production or antibiotic resistance."
Basically the article is about being able to apply various processes to groups of organisms instead of individual ones, and then make sense of the resulting data via computer. Also the article itself is very low on actual information...
"You're right," Fisheye says. "I should have set it on 'whip' or 'chop.'"
You could use one of these (scroll down), for starters.
This is really a new paradigm for microbial ecology. Instead of worrying about how thousands of different species (most of them unknown) are interacting with each other, you can now think about what genomic and proteomic resources are present in a habitat. Think of the organisms themselves as just the bags that contain what you're really interested in looking at, and suddenly a lot of insights and high-throughput techniques open up to you.
...they create some bizarre mutant strain that runs amuck, "innocently" killing everything in sight...
There was a game called Spore being developed, you would took life from microbial stages of evolution to an interstellar civilization stage. what happened to it i wonder.
Read radical news here
The article was taken from a National Academies press release. Here's the full report, parts of which (maybe the whole thing? I didn't check) can be previewed as a pdf if you don't want to purchase the book.
Oh, and here's a brief (4-page summary) of the report.
Woulda been nice to have the source info in the summary...
"Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
US audience:
Don't tell any Republicans about this.
The prez is already concerned about the possibility, and I quote from a speech: "human-animal hybrids".
How do you extract dna from millions of microbes?
You use metagnomes. They're the same gnomes who carry out step 2. If they can figure out how to extract profit from underpants, they can figure out how to extract DNA from millions of microbes.
- None can love freedom heartily, but good men; the rest love not freedom, but license. -- John Milton
Old and Busted: PCR
The New Hotness: Shotgun Sequencing
The Craig Venter Institute's Global Ocean Sampling Expedition has been collecting Metagenomic samples for the past couple of years. Among other things the expedition has doubled the number of putative proteins. An excellent video from the expedition is available at http://plos.cnpg.com/lsca/webinar/venter/20070306/ index.html and a set of recently published papers from the expedition are available for free at http://collections.plos.org/plosbiology/gos-2007.p hp
A website hosting the data from the expedition catered towards use on metagenomic samples has been developed by the Venter institute and is available at http://camera.calit2.net/
You name it: genomics, proteomics, metabolomics, fluxomics, .... omics, ...omics. Now all over again: metagenomics, metaproteomics, metametabolomics, meta...omics,...., meta...omics.
This is ridiculous, it is all biology people, new fancy names dont mean anything. I suggest we do the same in physics, chemistry, geology, etc. Let us try it : nucleomics, atomomics, solidomics, mecanomics, electromagnetomics, qcdomics,fluidomics, statisticomics, oganochemicomics, biochemicomics. And then metanucleomics, metaatomomics, metasolidomics, metaelectromagnetomics, metaqcdomics, metafluidomics, metastatisticomics, metaorganochemicomics!, metabiochemicomics, meta... comics. This is HUGE!, It is great to be a scientist! In the end it is al comics!
Since it handles microbes and DNA, it's mildly related:
You know, pondering about evolution, there is only one thing I have difficulty understanding with evolutionism (which I am a strong proponent of). I don't know if you're a biologist or not, but if someone could give me a good explanation I would be glad.
In the case of social groups of insects, like bees and ants, you have different classes/groups of individual insects within one hive, some of which are highly specialised. I can't quite understand how that works, using darwinistic evolution. When one follows the theory of evolutionism with, say, mammals, it makes sense: a genetic change in sperm or egg can lead to an indivdual who is less or more adapted to their environment, and this indivdual passes those traits to his/her offspring.
But, in the case of social insects like ants, you have one queen (and usually one dar) who supplies all the sperm and eggs that the queen uses to create her offspring, resulting in sometimes very specialised ants/bees. But how did that specialisation come about in a heritary sense, when those specialised ants are unfertile, and can't reproduce themselves?
So, how does it work? Say, the queen lays an egg, which has a mutation in it, which evolves into a more specialised ant which is beneficial for the whole hive. Very well. The hive survives better through it. But HOW does that ant give its benefical adaptation/specialisation to any offspring, when it can't reproduce?
One could argue: a hive is like an organ on itself, and a mutation for an improved organ is also present in cells for other organs.
And well, yes, but that's because the DNA for that improved organ has its origin in the spermcel or eggcell (well, the mutation of their DNA, that is), comming from a parent organism. In the case of hive-insects, where the egg of the mutated-and-better-adapted worker-ant comes out, there is no way that infertile worker could be the parent to transmit his mutation throughout any other offspring. Thus, there is no parent - which is different with the analogy of the organs you gave. The right analogy would be, that a sudden mutation hits the organ (say, the heart) itself, and it starts working better (and thus, is beneficial).
But then the same problem arises; it's not possible for the mutation of the heart-organ, beneficial as it might be for the whole organism, to pass the mutation to any offspring, because it's *only a mutation happening in sperm and eggcells* which can provide the mechanism of transmitting a mutuation to any offspring. The mutation of the heart doesn't suddenly transfer, nor does it infuse itself into the DNA of the spermcell.
So, the main problem remains. To give a clear example of what I mean; let's say the ancestors of those ants were more simple, less specialised. At a certain moment, in the DNA of a queen-egg, there occurs a mutation; this mutuation turns out to be beneficial - say, the worker-ant develops an enzym which is far more efficient in providing digestable nutrients from raw food, for instance. Now, that ant lives its life, then dies...since workers are unfertile, they don't mate with the queen, and they don't pass on their beneficial mutation.
So how the heck did those specialised ants come to be, and how do they (the next generation) keep existing in the next hive(s)? Any biologists around who can give a clear explanation of how darwinistic evolution works with hive-insects?
--- "To pee or not to pee, that is the question." ---
PloS Biology just published a bunch of papers using metagenomics to study the ocean genome. They sailed a yacht from Nova Scotia to the South Pacific, stopping now and then to scoop up a bucket of sea water, filter out the microbes, extract DNA on mass and shotgun sequence them. They discovered enough new proteins to *double* the size of the GenBank database (molecular biology geeks will be impressed by this). Read all about it here. Or just read about it on our blog.
We recently had a speaker here to introduced us to the new methods of DNA sequencing that are so brilliant you might think we stole the tech from aliens. If you're interested, check out the 454 Life Sciences Corporation or THIS ARTICLE for a scoop on one such new method that'll knock your socks off if you're an old-school biologist. Their process (click through and read the slides) is light-years beyond where we were only 5 years ago. The speaker we had reported that their lab was able to sequence massive pools of DNA from bacteria that lives in our intestines (well, monkey intestines, but close enough) and were able to determine that we have upwards of 1000 different species of bacteria living in us, mostly likely helping our system.
To summarize the sequencing method very briefly and un-technically (if you want the tech, read the site above): it manages to sequence thousands of little pieces of DNA at once... something we had to do one at a time or with the best machines, 96 at a time with a good bit of manual labor. Now we're talking thousands at once, on one machine, in one reaction, on one array. Holy smokes. A single lab worker could potentially sequence more in a day than 10 people working for a month.
With new technology such as this, the thought of sequencing a person's entire Genome in an hour is far closer than we could have ever dreamed. We're talking a couple years here. A decade ago that thought was unimaginable and downright crazy talk. And as the article said, it can also give us glimpses into genetic interactions between organisms in populations from a perspective we could never see before. See "Lateral DNA Transfer: Mechanisms and Consequences".
You'd be surprised.
/. title, although a little bit different. Today's article is about analyzing lots of bacteria in a single sample to try to understand the subtle equilibrium in the bacterial flora, where our study did analyze lots of sample *in a whole population* in order to understand the dynamics of propagation and evolution of a common skin inhabitant (the S. Aureus is common, but not all people have the exact "family" on their skin. It's interesting to see how widely those family are present in the wild and with which proportion.)
:
Modern PCR kits have become so much robust that you can put almost anything at them, and they still manage to duplicate the exact piece of genes that you need, without much artifacts.
At the last lab where I worked we use to take bacterial colonies and shake them with microbeads and... and thats it.
We developed a fast, high throughput and dead-cheap methods for genotyping (ie.: puting into sub-families according to gene properties) of Staphylococus Aureus bacteria (a very simple and common bacteria, that simply lives on the skin of lot of people and is mostly harmless. But this bacteria can acquire very easily resisting capability against antibiotics and subsequently become a real problem in some more special part of a hospital).
This is the exact kind of studies as suggested by the
The method was dead simple
- take microbead (glass beads of micro-metric size. looks like sand. easy to clean : only needed to rince with concentrated acid)
- from a culture (for example : swabs that we let grow in a medium, or a few colonie from an old stock that we re-seeded on a petri dish) we take a few colonies.
- we put the beads and the colonies in some buffer inside a small flask.
- shake the bead throughly using something that can be described as a vibrator. (The bead shred everything inside : all the bacteria are turned into a big soup. bacterial genome can be cut in smaller pieces, but at least some pieces contain the interesting genes uninterrupted).
- put a small amount of that soup into an essay tube that contain the necessary reactant to do a PCR (enzyme, DNA primers/probes, nucleotide, buffer).
- run the PCR with a thermal cycler. (as the amount of soup is very small, the presence of proteins and such is insignificant and, as long there is DNA corresponding to the primers/probes, it will get copied exponentially by the PCR. In fact, the multiplication is so efficient that a couple of copies of the interesting gene in the soup is enough to generate 2^30 copies).
- now you have essay tubes where some gene where duplicated an incredible amount of time. If you are smart with the primers you choose, you could be very specific and copy gene that are only specific for certain "families" (somewhat. In fact we choose some varaible-lenght genes whose size vary between strains) and also test for less specific genes (common in all S. Aureus, to be sure that you did find some in your sample)
- You can test the results using something like capillary electrophoresis with lab-on-a-chips (you can do an electrophoresis to separate and check for the PCR results using a small piece of glass with microscopique channels carved on it)
- Add your result to a huge database to study population (of bacteria) across the human population.
The whole procedure doesn't cost much more than a few dollars per sample (great for big studies)
No more difficult than that.
The whole "DNA extraction" is just 1 single dead simple step where you turn everything into a soup using microbeads (technology as much complicated as the blender in your kitchen, only much smaller scale) and then count on the incredible sensitivity and specificity of the PCR reaction to sort the stuff.
Now for the ap
"Sufficiently advanced satire is indistinguishable from reality." - [Tips: 1DrYakQDKCQ6y52z6QbnkxHXAocMZJE61o ]
Abundance of material doesn't pose a problem. Soil samples are so abundant in diverse microorganisms that its actually a problem later on. For water sampling it is quite straight-forward to use tangential flow filters to collect sufficient biomass by simply processing the appropriate volume of water.
Of the shotgun sequencing type, most studies to date have been of marine organisms.
I'm not sure whether the above post should be marked "astroturfing" but it sure reads a little too positive.
454's sequencing technology is a welcomed addition to existing technologies, but don't believe the hype, particularly when the person talking has stock options.
The analysis of genomic sequencing data (metagenomics or otherwise) is highly benefited by large contiguous pieces or ideally whole contiguous genomes. Related to this and more fundemental is the fact that the shorter the pieces of DNA spat out by a machine the harder the problem of assembling them into larger contiguous chunks. This is due in part to the combinatorics of an alphabet made up of only 4 symbols but mainly the fact that genomic DNA contains many repeat structures even in lower organisms.
Without going into detail, it suffices to say that the longer the pieces (or "reads") produced by a sequencing machine, the easier the problem. Add to this the realities of sequencing errors and throw in metagenomics where you may have many organisms with almost the same genome, the problem gets quite hard.
Currently the large sequencing facilties that use 454 machines use them to complement their existing machines which produce 3-10 times longer reads (depending on who's talking). There are in fact papers investigating the ideal ratio of reads produced by new and old technologies.
Another factor to keep in mind is that, although the new high-throughput technologies (454 is the first to market, but not the only player) hold alot of promise, a large part of their appeal was going to be an enormous cost reduction. The problem is, so far that part of the equation hasn't met expectation. They are quite costly to run due to the cost of consumables and those prices are set by the manufacturer.
The advent of metagenomics is accentuating a sad trend in science: less lab work, more computers. Do not get me wrong, I feed my kids from the computer desk and I have never touched an "Eppendorf" or "Pipetteman" (not sure about spelling). In the race for grants we are chasing aggrandisement of the projects we are applying to NSF and DOE. More computers, more modeling instead of experimenting.
I have been reading scientific literature for almost 25 years and the tendency is clear: the results of "computer experemints" (read, modeling) are trusted more and more without any experimental verification. The procentage of sequences in GenBank and Refseq which function is determined only by homology to existing proteins grows. That means we are guessing the function of new proteins by comparing them to the proteins which function we also guessed by comparing to earlier proteins, etc...
Number of protein folds is limited: 700, 1000, 30000, does not matter: it is limited, but it does not mean the functions are limited in the same way. How on earth are we going to find out the function of completely new protein that have not enough similarity to anything in the database? We cannot do it on computers.
And obviously we do not have resources to research experimentally 1.5M genes in Refseq. So instead of blindly pumping more and more raw data into our RAID arrays, we need to be more focused on researching the genes, proteins, pathways that have a direct impact on medicine. You know, "stuff that matters".
I do not believe in karma. "Funny"=-6. Do good and forbid evil. Yours, Oft-Offtopic Flamebaiting Troll.
Original can be found here
Problem is, the insatiably curious people go into science or engineering or something like that. Teaching gives very few opportunities to satisfy one's curiosity -- at least in a professional capacity. I'm not making any claims about what teachers do in their spare time. And that's certainly not to badmouth teachers either; teachers who love what they do and teach with passion do more good in the world than almost anyone else in the world. But because teaching focuses on what's already known, the best it can hope to accomplish is to encourage the students who are already deeply curious by tantalizing them with hints at the fabulous depth of Human knowledge.
Thank you for the detailed response.... I wish I could mod it up. I hate to see someone put forth such effort for something thats' modded too low for most readers to see!
Sometimes the best solution is to stop wasting time looking for an easy solution.