5 ms·

Is this a joke?

by rvikmanis 11y ago

Is this a joke?

adrusi 11y ago
Yes.
88e282102ae2e5b 11y ago
No, but it's not as interesting as it sounds.
- theideasmith 11y ago
  Why not?
  - marktangotango 11y ago
    Two reasons I can think of; biochemical reaction pathways can be tremendously complex with subtle feedback mechanisms that are non obvious, secondly, DNA encodes mRNA that encodes proteins; determining protein folding from the sequence of DNA is exceeding difficult, so, just because you can 'write DNA programs' doesn't mean you can actually do anything with the result. Both of these factors taken together mean, that with current technology, it's really hard problem to modify DNA, to influence existing biochemical processes, or create new biochemical processes. I studied molecular biology in the 90's so I'm a bit out of date, but I believe this is still the state of affairs.
    - abecedarius 11y ago
      Engineering new circuits isn't the same kind of problem as understanding natural ones, just as designing a protein to fold predictably came many years ahead of predicting the folding of natural proteins. (The former started in the 80s, and the latter is afaik still very hard, as you say.) http://www.dna.caltech.edu/courses/cs191/index.html http://www.dna.caltech.edu/courses/cs191/index.html gets into some of the recent progress (under "Nucleic acid circuits"). That said, it's not my field and I get the impression they're talking more about in vitro work on the page I linked. Even if your circuits work all the time in the lab, in a cell I'd expect all kinds of things to mess with them.
      - jamessb 11y ago
        'Nucleic acid circuits'/'DNA circuits' are conceptually entirely different to 'genetic circuits'. In the former, you design sequences of DNA such that complementary base pairing means they can displace each other in cleaver ways. This lets you create some interesting things, like oscillators [1], amongst others [2]. These do not need any of the apparatus of the cell to function, so work in solution; indeed, if they were inside cells they would get digested by nucleases. The thermodynamics of DNA/RNA folding is fairly well understood, and the range of structures in much more limited than that of proteins. A major drawback of these circuits is that they function very slowly. By 'genetic circuits', people usually mean a genetic regulatory network [3] - essentially you combine existing genes in new ways, by chaing the regulatory sequences before each gene. For example, you can construct an oscillator from three genes by having the first repress the second, which represses the third, which represses the first [4]. Here you aren't designing new proteins (which is extremely hard), but rather modifying existing ones. Since these circuits require producing new proteins from DNA, they require RNA polymerase, the proteosome, ATP, the necessary monomers etc. so can only function inside a cell (or cell-free expression system containing these components). [1]: https://www.researchgate.net/publication/50304896_Programming_an_in_vitro_DNA_oscillator_using_a_molecular_networking_strategy_Mol_Syst_Biol_7466 https://www.researchgate.net/publication/50304896_Programmin... [2]: http://research.microsoft.com/en-us/projects/dna/ http://research.microsoft.com/en-us/projects/dna/ [3]: https://en.wikipedia.org/wiki/Gene_regulatory_network https://en.wikipedia.org/wiki/Gene_regulatory_network [4]: https://en.wikipedia.org/wiki/Repressilator https://en.wikipedia.org/wiki/Repressilator
  - 88e282102ae2e5b 11y ago
    It just automates what was previously something done manually. But it only works 75% of the time. It's a nice tool to have if this is your domain but it's not like you get any guarantees about success. Biology is still stubbornly complex.
    - 100ideas 11y ago
      75% success rate for systems with this complexity (>10 elements) is probably just as good if not better than what would be expected by designing “by hand,” and the latter approach does not scale past the current order of magnitude (to 100+ component designs). I think that’s their main argument.
      - jamessb 10y ago
        A major problem with further scale-up is the availability of parts. In an electrical circuit the signals voltages that are constrained to wires; in a a genetic circuit the signals are concentrations of proteins/compounds that are diffusing around the cell. This gives a problem: to have independent logic gates you need transcription factors that will bind to distinct promoter sequences, without crosstalk. If you're doing this in a cell rather than cell-free system you also need to avoid crosstalk with the host cell. The problem isn't so much in designing the circuit abstractly as finding specific parts with which to construct it. One approach is to partition the circuit across multiple cells [0, 1]. [0]: http://www.nature.com/nature/journal/v469/n7329/full/nature09565.html http://www.nature.com/nature/journal/v469/n7329/full/nature0... [1]: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004685 http://journals.plos.org/ploscompbiol/article?id=10.1371/jou...
        100ideas 10y ago
        Eukaryotic cells solve the "crosstalk problem" by building the control regions that regulate gene expression out of modular, hierarchically-organized binding sites for multiple transcription factors (TFs). In prokaryotic systems there is (in a very approximate, generic sense) a one-to-one correspondence between the concentration of a particular transcription factor and the expression (or repression) of the genes downstream of the binding site for that transcription factor. The control regions in eukaryotic genomes have binding sites for multiple transcription factors, combinations of which may become binding sites for other transcription factors (larger TFs which bind to certain combinations of smaller TFs), etc. In this way, the specific sequence of TF binding domains in the regulatory region of a eukaryotic gene provides a particular and potentially unique "address" in "Transcription Factor State Space" by which the gene can be controlled. For more information on this amazing topic, check out "The Regulatory Genome" by Eric H. Davidson. Here is an excerpt from the first page of chapter 4: "Whatever their extent, however, development gene regulatory networks have an internal structure, in that they are composed of diverse kinds of modular parts and connections among these parts. Here 'modular' takes on a simple functional meaning: it is used to denote small subsets of genes within the overall network that together execute given 'jobs,' e.g., to operate a certain differentiation gene battery, or to transduce an extracellular signal into a certain regulatory state. In what follows, sets of regulatory genes that execute modular functions are usually referred to as constituting 'subcircuits' of the network, because as we shall shortly see they are 'wired together' within the subcircuit by their gene regulatory interactions. Just as the target site inputs of an individual cis-regulatory [note: cis- prefix in this context indicates gene regulation via non-expressed sequences of DNA proximal to a gene in the genome] module are integrated to generate novel outputs according to its genomic design, so the outputs of these subcircuits are integrated to generate logic outputs which depend on their organization, that is, their wiring architecture." - https://books.google.com/books?id=F2ibJj1LHGEC&pg=PA126 https://books.google.com/books?id=F2ibJj1LHGEC&pg=PA126 [edit 1: added link to google books & excerpt]
  - dnautics 11y ago
    Nest three while loops and a five if...then conditionals and see if you get what you expect.
- allisthemoist 11y ago
  The most intricate April Fools joke this year

Is this a joke?

adrusi 11y ago

Yes.

88e282102ae2e5b 11y ago

No, but it's not as interesting as it sounds.

theideasmith 11y ago
Why not?
- marktangotango 11y ago
  Two reasons I can think of; biochemical reaction pathways can be tremendously complex with subtle feedback mechanisms that are non obvious, secondly, DNA encodes mRNA that encodes proteins; determining protein folding from the sequence of DNA is exceeding difficult, so, just because you can 'write DNA programs' doesn't mean you can actually do anything with the result. Both of these factors taken together mean, that with current technology, it's really hard problem to modify DNA, to influence existing biochemical processes, or create new biochemical processes. I studied molecular biology in the 90's so I'm a bit out of date, but I believe this is still the state of affairs.
  - abecedarius 11y ago
    Engineering new circuits isn't the same kind of problem as understanding natural ones, just as designing a protein to fold predictably came many years ahead of predicting the folding of natural proteins. (The former started in the 80s, and the latter is afaik still very hard, as you say.) http://www.dna.caltech.edu/courses/cs191/index.html http://www.dna.caltech.edu/courses/cs191/index.html gets into some of the recent progress (under "Nucleic acid circuits"). That said, it's not my field and I get the impression they're talking more about in vitro work on the page I linked. Even if your circuits work all the time in the lab, in a cell I'd expect all kinds of things to mess with them.
    - jamessb 11y ago
      'Nucleic acid circuits'/'DNA circuits' are conceptually entirely different to 'genetic circuits'. In the former, you design sequences of DNA such that complementary base pairing means they can displace each other in cleaver ways. This lets you create some interesting things, like oscillators [1], amongst others [2]. These do not need any of the apparatus of the cell to function, so work in solution; indeed, if they were inside cells they would get digested by nucleases. The thermodynamics of DNA/RNA folding is fairly well understood, and the range of structures in much more limited than that of proteins. A major drawback of these circuits is that they function very slowly. By 'genetic circuits', people usually mean a genetic regulatory network [3] - essentially you combine existing genes in new ways, by chaing the regulatory sequences before each gene. For example, you can construct an oscillator from three genes by having the first repress the second, which represses the third, which represses the first [4]. Here you aren't designing new proteins (which is extremely hard), but rather modifying existing ones. Since these circuits require producing new proteins from DNA, they require RNA polymerase, the proteosome, ATP, the necessary monomers etc. so can only function inside a cell (or cell-free expression system containing these components). [1]: https://www.researchgate.net/publication/50304896_Programming_an_in_vitro_DNA_oscillator_using_a_molecular_networking_strategy_Mol_Syst_Biol_7466 https://www.researchgate.net/publication/50304896_Programmin... [2]: http://research.microsoft.com/en-us/projects/dna/ http://research.microsoft.com/en-us/projects/dna/ [3]: https://en.wikipedia.org/wiki/Gene_regulatory_network https://en.wikipedia.org/wiki/Gene_regulatory_network [4]: https://en.wikipedia.org/wiki/Repressilator https://en.wikipedia.org/wiki/Repressilator
- 88e282102ae2e5b 11y ago
  It just automates what was previously something done manually. But it only works 75% of the time. It's a nice tool to have if this is your domain but it's not like you get any guarantees about success. Biology is still stubbornly complex.
  - 100ideas 11y ago
    75% success rate for systems with this complexity (>10 elements) is probably just as good if not better than what would be expected by designing “by hand,” and the latter approach does not scale past the current order of magnitude (to 100+ component designs). I think that’s their main argument.
    - jamessb 10y ago
      A major problem with further scale-up is the availability of parts. In an electrical circuit the signals voltages that are constrained to wires; in a a genetic circuit the signals are concentrations of proteins/compounds that are diffusing around the cell. This gives a problem: to have independent logic gates you need transcription factors that will bind to distinct promoter sequences, without crosstalk. If you're doing this in a cell rather than cell-free system you also need to avoid crosstalk with the host cell. The problem isn't so much in designing the circuit abstractly as finding specific parts with which to construct it. One approach is to partition the circuit across multiple cells [0, 1]. [0]: http://www.nature.com/nature/journal/v469/n7329/full/nature09565.html http://www.nature.com/nature/journal/v469/n7329/full/nature0... [1]: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004685 http://journals.plos.org/ploscompbiol/article?id=10.1371/jou...
      - 100ideas 10y ago
        Eukaryotic cells solve the "crosstalk problem" by building the control regions that regulate gene expression out of modular, hierarchically-organized binding sites for multiple transcription factors (TFs). In prokaryotic systems there is (in a very approximate, generic sense) a one-to-one correspondence between the concentration of a particular transcription factor and the expression (or repression) of the genes downstream of the binding site for that transcription factor. The control regions in eukaryotic genomes have binding sites for multiple transcription factors, combinations of which may become binding sites for other transcription factors (larger TFs which bind to certain combinations of smaller TFs), etc. In this way, the specific sequence of TF binding domains in the regulatory region of a eukaryotic gene provides a particular and potentially unique "address" in "Transcription Factor State Space" by which the gene can be controlled. For more information on this amazing topic, check out "The Regulatory Genome" by Eric H. Davidson. Here is an excerpt from the first page of chapter 4: "Whatever their extent, however, development gene regulatory networks have an internal structure, in that they are composed of diverse kinds of modular parts and connections among these parts. Here 'modular' takes on a simple functional meaning: it is used to denote small subsets of genes within the overall network that together execute given 'jobs,' e.g., to operate a certain differentiation gene battery, or to transduce an extracellular signal into a certain regulatory state. In what follows, sets of regulatory genes that execute modular functions are usually referred to as constituting 'subcircuits' of the network, because as we shall shortly see they are 'wired together' within the subcircuit by their gene regulatory interactions. Just as the target site inputs of an individual cis-regulatory [note: cis- prefix in this context indicates gene regulation via non-expressed sequences of DNA proximal to a gene in the genome] module are integrated to generate novel outputs according to its genomic design, so the outputs of these subcircuits are integrated to generate logic outputs which depend on their organization, that is, their wiring architecture." - https://books.google.com/books?id=F2ibJj1LHGEC&pg=PA126 https://books.google.com/books?id=F2ibJj1LHGEC&pg=PA126 [edit 1: added link to google books & excerpt]
- dnautics 11y ago
  Nest three while loops and a five if...then conditionals and see if you get what you expect.
allisthemoist 11y ago
The most intricate April Fools joke this year