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Researchers Build Logic Gates With RNA

Soulskill posted more than 5 years ago | from the finally-a-use-for-that-pesky-rna dept.

Biotech 58

Ars Technica reports on research out of Cal Tech where scientists were able to create logic gates out of RNA molecules. Thus far, they've demonstrated AND gates and OR gates, with work proceeding on more complicated systems. The work shows promise for ability to easily detect the presence of particular chemicals. The abstract from the scientists' paper is available at Science. Quoting Ars: "Detecting tetracycline isn't especially interesting, but RNA that binds to specific small molecules is actually relatively easy to make; repeated rounds of amplification and selection for binding can evolve these RNAs in a couple of days. This means that, in a matter of days, researchers can grow yeast colonies that glow in response to a variety of chemicals, or even to combinations of chemicals. More complicated circuits should be possible if the ribozymes are inserted into messenger RNAs that encode transcription factors, which could, in turn, regulate genes that encode yet other ribozymes."

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Nice... (5, Funny)

Anonymous Coward | more than 5 years ago | (#25422831)

But how long before it runs Linux?

Re:Nice... (2, Funny)

Gerafix (1028986) | more than 5 years ago | (#25422847)

Sooner than you might think. But beware of kernel panics...

Re:Nice... (1)

s4ltyd0g (452701) | more than 5 years ago | (#25423565)

let alone viruses...

Re:Nice... (1)

LrdDimwit (1133419) | more than 5 years ago | (#25425331)

Well, a kernel panic would be bad ... but what you really gotta watch out for? while(true) {fork(); }

I think Michael Crichton might have written a book about this already ...

Re:Nice... (1)

cangrejoinmortal (1315615) | more than 5 years ago | (#25437645)

Do we have to fear? isn't life but a chemical computer which performs basically the computation you describe, crudely known as 'fork bomb'?

Re:Nice... (5, Funny)

fluffybacon (696495) | more than 5 years ago | (#25422881)

2008 will be the year of Linux on your face!

Re:Nice... (1)

master5o1 (1068594) | more than 5 years ago | (#25423655)

2009 - Year of the face/palm linux!

Re:Nice... (1)

Anpheus (908711) | more than 5 years ago | (#25426553)

That's GNU/face/palm/linux, you insensitive clod.

Re:Nice... (1)

master5o1 (1068594) | more than 5 years ago | (#25428963)

I think RMS will be please to know that Guanine has been renamed to GNUanine for any bio-logical device running GNU- stuff (GNU/Linux). Of course, he may not be pleased with the idea of controlling biological species as if they were electronic systems, being a paranoid insecure coot. Ah well.

Re:Nice... (1)

bwashed75 (1389301) | more than 5 years ago | (#25434205)

2008 will be the year of Linux in my ass!

Formally, this is caused by resonance (0)

Anonymous Coward | more than 5 years ago | (#25422841)

The scientists want us to use RNA, but RNA is just a cheap knockoff of DNA, which is much better because it is deoxygenated and has to be made iun a clean room like powerful computer chipes. I'll be waiting for version 2.1, because this is another buggy opensource thing with absolutely no documentation. Give me Apache any day, it's p[roven rock solid as long as you don't use RNA or MySQA. Also, this could become viruses, which are bad because they can be sick like bactiria.

Uh oh... (1)

exscape (1302123) | more than 5 years ago | (#25422851)

I guess this means skynet will be part-biological.

Re:Uh oh... (4, Insightful)

Cylix (55374) | more than 5 years ago | (#25422873)

Completely wrong track I'm afraid.

Skynet is more cell phones, cash registers and anything with a system.

Matrix was more humans are batteries, but in this case we get to be both networked pods and large D cells.

Yes, it could be said that the matrix villains are far more green then the terminators. Marketing research shows that hippies prefer matrix type overlords.

You nerds love it (-1, Offtopic)

Anonymous Coward | more than 5 years ago | (#25422869)

You nerds love it [goatse.cz]

Re:You nerds love it (0)

Anonymous Coward | more than 5 years ago | (#25422921)

But not as much as you. So is that your ass?

This means also that (1)

VincenzoRomano (881055) | more than 5 years ago | (#25422871)

even my stupid neighbour has plenty of intelligence!

Re:This means also that (1)

chemisus (920383) | more than 5 years ago | (#25423539)

or at least some form of logic...

Implications (4, Funny)

The Clockwork Troll (655321) | more than 5 years ago | (#25422875)

Perhaps the results of this research can be used to create biological instances of the satisfiability [wikipedia.org] problem.

If satisfiability can be reduced to DNA transcription in polynomial time, then we could genetically engineer colonies of randomly poisoned cats in boxes to solve NP-complete problems.

I wonder (1)

Psychotria (953670) | more than 5 years ago | (#25422885)

If this can (after more research) be used as a basis for cell 'monitoring', that, in itself would be amazing

Our ability to transmit information to and from living systems, and to process and act on information inside cells

From that quote I would guess that, yes, it can be extended; but I am at home and cannot read the whole Science article. More interesting is the possibility of cell manufacturing... factories that churn out cells with particular attributes and particular reactions on demand. That might be a bit far into the future though and the process may need to branch and include DNA. Nonetheless, this research is very interesting to me. The thought that we can create RNA that behaves in a known way given a certain stimulus (or set of stimuli) is incredible.

Can the research be expanded to include all the logical operators? (At this point I'd have to guess the answer is yes). I am not sure what this implies... it's exciting though.

I don't know if they need a cell (4, Interesting)

Moraelin (679338) | more than 5 years ago | (#25422957)

1. Actually, I don't know if they really need a cell.

Even from the viewpoint of life evolution on Earth, it all started with some self-replicating ribosyme that "lived" perfectly well in the soup of aminoacids and nucleotides around it. The cell was just an increasingly complex test tube around that reaction, complete with increasingly complex ways of regulating the exact composition of the contained drop of sea water.

I can see how that was an advantage to evolve, in a primordial soup that was hit and miss anyway and probably (very slowly) degrading in quality over time. But in a lab, we can do that regulating artifficially. Admittedly, using a cell might be cheaper, but we can do without it too.

And indeed there is plenty of organic stuff we already do without a cell. E.g., detecting certain DNA sequences is done via enzymes which bind exactly to one sequence, and start replicating it until it's enough to be detected. We don't really build specialized cells for that.

2. Actually, to me another aspect is more interesting there: the fact that it's all done with RNA.

Proteins already _do_ exactly what these guys seem to do: bind only to certain mollecule configurations, but not to others. You can see it as logic operations and whatnot, but really it's all chemistry and that's all it does: bind only to certain mollecules, but not to others. It's a bit like saying that a keyring with two keys is a mechanical OR gate: it unlocks a lock that matches either key 1 or key 2. It's simultaneously technically true, and a bit misleading.

But there's a more interesting aspect to it: your body usually uses proteins for that, and DNA/RNA is just a way to encode a protein which will actually do the matching. E.g., those enzymes I mentioned, are proteins. They do all the heavy duty chemistry, from processing the cell's "food", to regulating what goes in or out, to destroying all chemicals which are non-polar and pass right through the cell wall instead of being regulated by the protein valves on the wall, to movement, to DNA repairs, to regulating what other proteins are built and where do they go.

As long as that's all the model we know, that needs a rather complex initial configuration for the start of life. You need something that's capable not only of replicating itself, but also of encoding proteins. It's already a bit too big an incredible machine, and appearing out of nowhere, even after billions of years and trillions of tries per second, still is a damn improbable event.

But that everything can be done via RNA only, that opens a whole new possibility. We already know that RNA can replicate itself. If it can also take the functions of a protein, offers a much simpler initial configuration for life. It's entirely possible that assembling proteins came later, as a better replacement, much like DNA later replaced RNA as the encoding of choice. The first cells could have been RNA-only, but could still have a metabolism and be able to regulate themselves well enough.

I find that fascinating.

Re:I don't know if they need a cell (1)

Psychotria (953670) | more than 5 years ago | (#25423047)

I don't know if they need a cell either. What I find interesting is that this may become a way of monitoring cell processes. I.e. a way of monitoring that can do more than we currently can. You said it:

But there's a more interesting aspect to it: your body usually uses proteins for that, and DNA/RNA is just a way to encode a protein which will actually do the matching. E.g., those enzymes I mentioned, are proteins. They do all the heavy duty chemistry, from processing the cell's "food", to regulating what goes in or out, to destroying all chemicals which are non-polar and pass right through the cell wall instead of being regulated by the protein valves on the wall, to movement, to DNA repairs, to regulating what other proteins are built and where do they go.

_That_ is what I am interested in seeing elucidated more than current technology can. I don't know if this research can do it, but it, certainly, seems like it's along the right path.

Re:I don't know if they need a cell (2, Informative)

Anonymous Coward | more than 5 years ago | (#25427381)

IAACB (I Am A Chemical Biologist), and your enthusiasm is great, but there are just a few gaps in your understanding that modern biochemistry is just starting to fill in...
The classical idea that RNA is nonfunctional has really more and more fallen by the wayside, especially since the crystallization of the eukaryotic ribosome. More and more, we understand that RNA, while not as robust at doing chemistry as proteins, is really a very powerful tool within the body and life in general. One recent discovery is that of native aptamers - natural pieces of the 'noncoding' regions of mRNA that bind small molecules to initiate or repress transcription. More than that, the ribosome itself is a ribozyme - proteins are built entirely using RNA machinery!
However, the real problem with noncellular ribozyme stuff is that, in general, ribozymes are very 'gooey' and very 'sticky', eg they're much less robust than proteins at working outside their native environments under tight regulation. Additionally, they're not very stable within the cell itself - they're really prone to getting chopped up, whereas folded proteins have extremely long half lives. All in all, the overall consensus is that RNA is an excellent research tool, but that Ribozymes and Aptamer Bioswitches are unlikely to be of great commercial use. Otherwise, all of us working on making protein systems to do nearly the same thing would look rather silly. :-P

Re:I don't know if they need a cell (1)

WhiteHorse-The Origi (1147665) | more than 5 years ago | (#25428479)

The whole point of the article is that they can (possibly)construct synthetic RNA that would regulate gene expression. The fact that they have linked computation to gene expression means they can use computer logic to synthesize RNA that would either express a gene or suppress it; and there is an exact method for doing that now.

Before this, it was a kind of guessing game where they could inhibit a gene but it would turn on expression of some other gene like "violent aggression". I assume this will eventually spin off into a device which takes a sample of your DNA and spits out some mRNA that will fix any genetic problems(or suppress it until you get your next injection). It's gene therapy for the masses... Now they just need a computational model which works for the entire human genome. I just hope they don't use .net to program it: "We're sorry, you'll have to wait 6 years for the calculation to complete".

Re:I don't know if they need a cell (1)

Bazer (760541) | more than 5 years ago | (#25432087)

I find that fascinating.

I disagree.

Personally, I find that completely awesome.

But what about NAND? (1)

ricegf (1059658) | more than 5 years ago | (#25422925)

ANDs and ORs are nice, but what about a NAND (Not AND)? Give me a NAND, and I can implement any Boolean equation.

Re:But what about NAND? (1)

tsjaikdus (940791) | more than 5 years ago | (#25423259)

In any other industry you don't need logic gates perse to build something that does arithmetic. It's the electronics industry that defines the NAND gate as the primary building block, because chips are made with that specific technology.

It's really all about shifting bit from one place to the other. Gates are only a convenient way to do this.

Re:But what about NAND? (3, Informative)

Anonymous Coward | more than 5 years ago | (#25423689)

You didn't really get it.

With a NAND (or a NOR), you can implement any logic function.

NOT(x) = NAND(x,x)

Now that we have a NOT gate using NAND only, we can use it to implement AND:

AND(x,y) = NOT(NAND(x,y))

Using AND and NOT (which only use NAND), you can implement a OR:

OR(x,y) = NOT(AND(NOT(x),NOT(y)))

You can't do this with AND, OR, or combinations of the two. Specifically, you can't use them to implement a NOT.

Re:But what about NAND? (1)

tsjaikdus (940791) | more than 5 years ago | (#25424111)

I'm just adding that gates are not a prerequisite for building something that can calculate. People often 'prove' that once you have your basic gate(s), you can thus also build a computer. The thing is that in the chip making industry gates are very useful. But in other fields of industry (biological, chemical, mechanical) gates may not be the best building block.

Re:But what about NAND? (1)

ricegf (1059658) | more than 5 years ago | (#25424891)

Of course. In high school, I created a gate-less electrical calculating device for a science fair project. But according to the summary, the article is about building logic gates with RNA. I was commenting in that vein.

Another way to calculate with RNA is to construct a living creature. Humans calculate, for example (well, at least some of us). So do chickens, dolphins, and various primates, or so I read. I bet my dog could, if some roasted meat was involved. :-)

Re:But what about NAND? (1)

RockDoctor (15477) | more than 5 years ago | (#25430141)

Another way to calculate with RNA is to construct a living creature.
[SNIP]
  I bet my dog could, if some roasted meat was involved. :-)

Why roasted ... ah, your dog has never encountered raw meat. Or at least, never encountered it in the context of "food".

Which is sadly plausible.
I remember being astonished the first time I encountered two kids (my sister's first two step kids) who didn't recognise a lump of coal. I wouldn't have been surprised that they didn't recognise it's significance (as part of the New Year first-footing pocketful, along with yourself, a poke of salt, a loaf of bread and a bottle of whiskey), but the astonishing thing was that by the ages of IIRC 6 and 8 they hadn't encountered a lump of coal before. Town kids in the age of central heating, but they'd never once been to a house with a Real Fire working, or seen a fire being laid.

Re:But what about NAND? (1)

ricegf (1059658) | more than 5 years ago | (#25430329)

Huh? I live in Texas - my dog kills and eats a variety of wildlife. But she prefers her meat roasted. Don't you??

Re:But what about NAND? (1)

RockDoctor (15477) | more than 5 years ago | (#25431189)

Huh? I live in Texas - my dog kills and eats a variety of wildlife.

That wasn't present in your posting ; from the characters on screen you could just as well have been living on the 17th floor of a tower block in the heart of a big conurbation - like Houston, for example - with your neighbour having a de-clawed cat who's never been out of the apartment.

But she prefers her meat roasted. Don't you??

NULL - no preference. It's food. It all comes out (of me) the same.

Re:But what about NAND? (1)

tsjaikdus (940791) | more than 5 years ago | (#25424193)

As an example, Babbage invented an anticipatory carriage that added all carries (40 or 50 in his machine per register) simultaneously. In electronics they use something similar which is called a look ahead carry. But it will typical add 4 carries at once (some other techniques exist to speed up things, but in the end you'll always use some translation mechanism that ripples a carry). Babbage's mechanical solution really did not ripple. It was later also used by Wiberg's difference engine.

Re:But what about NAND? (2, Insightful)

cryptor3 (572787) | more than 5 years ago | (#25423833)

Why restrict them to discovering a nand implementation? I was going to ask how close they were to implementing "not".

I'd rather ask the less restrictive question of how close they are to implementing a functionally complete set of gates in their process technology.

So for example this could be any of {nand}, {nor},{and,or,not}.

After all, it could be that in the RNA domain, building things out of all NANDs just isn't as efficient (in whatever sense they mean) as in static CMOS.

Re:But what about NAND? (0)

Anonymous Coward | more than 5 years ago | (#25424127)

RTFA, they have AND, NOR, NAND, and OR gates.

Re:But what about NAND? (1)

ricegf (1059658) | more than 5 years ago | (#25424843)

You must be new here.

Boolean Logic (2)

discards (1345907) | more than 5 years ago | (#25422933)

Why are they working on more complex systems? If they already have AND and OR, all they need is a NOT and they can make any other type of gate

Re:Boolean Logic (1)

Psychotria (953670) | more than 5 years ago | (#25423081)

I would imagine that NOT is implicit already (i.e. if A || B == false then it's !A and !B)

Re:Boolean Logic (1)

Psychotria (953670) | more than 5 years ago | (#25423099)

My last comment is obviously wrong. All that can be said is that it's NOT A and NOT B. But my original meaning still stands... they can infer NOT, and I can imagine the research easily implenting the NOT operator.

Re:Boolean Logic (3, Funny)

eric-x (1348097) | more than 5 years ago | (#25423439)

> My last comment is obviously wrong.
> But my original meaning still stands.
1.post theory and proof
2.retract proof and state that the theory is still valid.

Interesting concept you have there...

Thank Jessica Simpson! (1)

longhairedgnome (610579) | more than 5 years ago | (#25422953)

Detecting tetracycline isn't especially interesting

But after applying said tetracycline, our friends asking where our acne went will be.

Promising technologies, or not? (1)

Chrisimo (1388587) | more than 5 years ago | (#25422961)

3D Processors, Quantum Computers, DNA/RNA based Computers. A lot of progress is being made in these fields, it seems. But how many of them will actually make it into usable devices, if any?

Re:Promising technologies, or not? (1)

harry666t (1062422) | more than 5 years ago | (#25423091)

> But how many of them will actually make it into usable devices, if any?

They're irrelevant until they speak x86.

Re:Promising technologies, or not? (1)

tsjaikdus (940791) | more than 5 years ago | (#25423379)

You're right, we should stop all R&D right now. Until we know for sure that some usable devices will come out of it. Like the IKEA Three-seat sofa with long cover white.

Re:Promising technologies, or not? (0)

Anonymous Coward | more than 5 years ago | (#25423197)

Do you really want a computer that would go off in the heat and start smelling?

concentration camps, secret police, evesdropping (-1, Offtopic)

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Stem Loop DNA Logic Gates (1)

Christopher_Olah (1317943) | more than 5 years ago | (#25423263)

A similar technology is DNA stem-loop logic gates [unm.edu] . Theye were used to make MAYA and MAYA II [wikipedia.org] , a DNA computer that could play tic-tac-toe.

Closer to the event (0)

Anonymous Coward | more than 5 years ago | (#25423337)

A) We're closer than ever to "The Blob" [wikipedia.org] . With all the other apocalypses out there, xombie or otherwise, just waiting to happen and getting kinda bored of waiting in line...

B) (it's stronger than me, I can't resist..... )
      Brilliant!

C) My personal hack willl involve a pigment-altering retrovirus stimulated by drug abuser's insides.

      Oh, I dunno. Green is neat, but already overdone. Blue is too elegant - or cute. Red lacks imagination. Well, in matters fashion, ask the [google.com] French [google.com] . The polka-dots seem quite nice.

Yes, but... (1)

fph il quozientatore (971015) | more than 5 years ago | (#25423529)

Do you run linux?

Oh no! (0)

Anonymous Coward | more than 5 years ago | (#25423571)

Cyborgs!

Insider knowledge that the work is BS ... (2, Informative)

Anonymous Coward | more than 5 years ago | (#25423897)

Yes, yes, it looks and sounds cool and that's precisely why it was accepted into Science, but if you look closer at the results then you'll be greatly disappointed.

Why? Their RNA switches don't really perform as logic gates. When we think of logic gates, we think that the "signal" -- voltage in the case of electronic circuits or the production of a reporter gene in this case -- will have a clear difference between the "ON" and "OFF" states... 1 and 0. Electronic circuits are designed so that the voltages that represent the 1 and 0 are very, very different.

Unfortunately, these RNA switches do not have a clear separation between the ON and OFF states. The authors manipulate their data using disingenuous techniques that mislead the reader (to say the least!). Let me give you an example. When the RNA switch is ON, then the gene expression reporter will have an output of (for example) 1030. When the RNA switch is OFF, then the reporter will output 1000. The authors will report this as a 30 "unit fold change in device" or some other crappy made up unit.

Unfortunately, you can't use this RNA switch to DO ANYTHING that the authors say it can do. If you put another gene under control of this RNA switch then the "OFF" value will be so high that the gene will effectively be "ON". When the RNA switch is turned "ON" the change in gene expression will be so small compared to the baseline that the actual physiological effect will be negligible.

This is not the first time that the authors have mislead readers by manipulating their data (see their previous PNAS paper) and the LEADERS in the RNA switch field have vigorously complained that their work does not actually solve the RNA switch problem --- it just changes the way that the data is analyzed to make it appear that some problem was solved. Eventually, other scientists will discover the falsehoods and heads will roll.

This is a sad day for Science (both the journal and the pursuit thereof).

Re:Insider knowledge that the work is BS ... (1)

Intron (870560) | more than 5 years ago | (#25425181)

"When the RNA switch is ON, then the gene expression reporter will have an output of (for example) 1030. When the RNA switch is OFF, then the reporter will output 1000."

So you are saying that a reporter has a great deal of bias? What else is new?

What's the advantage? (1)

KeithIrwin (243301) | more than 5 years ago | (#25424393)

We already have DNA-based computing. Google "bacteria computer" or "bacterial computer". These are based on building DNA sequences which get up-regulated or down-regulated in the presence of certain chemicals. By joining these sequences together with sequences which produce the chemicals, they form logic gates. Researchers have been doing this for several years.

So what's the advantage of using RNA to build circuits? The article doesn't seem to explain what the point of this is, how it would be applied, or how it's different from DNA-based cellular computing.

What kind? (0)

Anonymous Coward | more than 5 years ago | (#25424677)

What kind of logic did come out? Male or female?

OT Rant (1, Informative)

Anonymous Coward | more than 5 years ago | (#25425055)

Gaah! This pisses me off every time I see it. I've got two degrees from the California Institute of Technology, and it's Caltech, dammit, not "Cal Tech". Get it right!

How To Kill The Mood (1)

hyades1 (1149581) | more than 5 years ago | (#25425309)

"What's that glow?"

"Um...did I mention that I have a bit of a yeast infection?"

Great for homebrewers! (2, Interesting)

unassimilatible (225662) | more than 5 years ago | (#25425549)

This means that, in a matter of days, researchers can grow yeast colonies that glow in response to a variety of chemicals, or even to combinations of chemical

As a homebrewer, there are lots of chemicals that show up in beer, some good, some bad. It would be great to modify a strain of yeast that would glow when diacetyl or some other chemical was present.
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