Researchers Build Logic Gates With RNA 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."
Re:But what about NAND? (Score:3, Informative)
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.
Insider knowledge that the work is BS ... (Score:2, Informative)
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).
OT Rant (Score:1, Informative)
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!
Re:I don't know if they need a cell (Score:2, Informative)
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... :-P
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.