Gating functions in protein networks

Lord Snooty bonzo at dog.com
Thu Jul 31 10:57:37 EST 2003


"Gordon D. Pusch" wrote:

> Dan <dmb at mrc-dunn.cam.ac.uk> writes:
>
> > I think you can generate all logical functions using
> > just a simple combination of lesser functions, but I
> > forget which.
>
> NAND (NOT(a AND b)) will work. Also NOR (NOT(A OR b)).  Also the
> "Sheffer stroke," <http://www.wikipedia.org/wiki/Sheffer_stroke>.
> There are several other possibilities. To build a NOR gate,
> insert two or more dissimilar repressor binding sites in between
> its promotor binding site and the gene; if a repressor protein
> binds to any of them, it shuts off transcription of the gene.
> (Of course, the boolean response will be "softened" due to chemical
> kinetics, but that's just a fact of life --- in both senses of the phrase! :-/)
>
> -- Gordon D. Pusch
>
> perl -e '$_ = "gdpusch\@NO.xnet.SPAM.com\n"; s/NO\.//; s/SPAM\.//; print;'

Thanks! This is exactly the kind of information I'm looking for. You've described a
plausible physical model for implementation of a NOR gate. My only follow-up
question would be whether we in fact observe this in specific instances, for any
known genes?

The NAND and the "Sheffer stroke" turn out to be identical (I have experience in
digital logic design and so I had to look that up).
Is there a plausible physical mechanism for this too? A physical example?

Finally, as regards other Boolean functions, I don't think things can get too
complex so as to embrace all possible functions, for two reasons:
1. We express inputs and outputs to be either inverting or noninverting - this cuts
down the possible truth tables considerably in any case (there are 2^2^2 = 16
possible truth tables for a 2-input gate).
2. We model the proteome expression profile in the following way:
- use RNAi or a similar technique to inhibit translation of one gene at a time for
the subset of genes for which we wish to reverese engineer the circuit.
- measure resultant proteome expression profile for each inhibition in turn, thus
creating a table
- express in the table the activity of a particular protein as either Fully OFF,
Reduced, Enhanced, Fully ON.
Thus we are only trying to determine, per inhibited protein, which other proteins
are directly hooked to its associated "logic gate" in the genome transcription
machinery. It is unlikely that such gates have a high input signal count, but I
confess I am not aware of any maximum number found thus far for maximum input
signal count, nor less do I know the physical basis in terms of actual
transcription machinery that would occasion this...except the example you quote
above, and I don't yet have your answer on whether this is in fact found _in vivo_,
or is merely a theoretical construct of a possible mechanism.

Note that this approach is a first-order stab at a reverse-engineered circuit. It
neglects completely the extra (and very useful) information afforded by the
time-dependent behaviour of the circuit, with the corresponding usage of coupling
constants and differential equations. In an engineering sense, I am interested in
deducing the "DC" circuit properties (and most importantly, the topology of the
interconnections and their connection logic), and the dynamic second phase would
putatively build on that DC basis of understanding to complete the analysis by
filling in the coupling and time constants via "AC" analysis.

-Andrew




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