I just finished a textbook that Drew Endy gave me on the design principles of biological circuits.

There is a fascinating section describing how the transcription networks of E.Coli (the common bacteria in your gut) robustly build electric flagella motors on demand, and a navigation system that senses food gradients across distances larger than the bacteria itself. It then moves at 30 body lengths per second.

It’s an interesting case study in gene transcription networks. When E.Coli is bathed in nutrients, it focuses energy on cell division (growth) and not movement. With a lack of nutrients, a genetic trigger induces the manufacture of several helical propellers (flagella) to enable it to swim to a better life.

In the diagram above, you see the 45nm wide, 100 Hz proton-pump rotary motor, as it is assembled in stages from 30 different proteins (text labels above). The motor and flagellum tail are hollow allowing each protein to self-assemble in sequence as they move down the assembly line straw.

Two transcription factors, let’s call them X and Y, regulate the six operons (gene clusters Z1 to Z6) to produce all of the proteins in the proper sequence. Master regulator X activates Y and both jointly activate the sequence of six operons Z1 – Z6, in order, with logical OR gate inputs. The signaling network is a classic multi-output feed-forward loop, common in biological networks, especially sensory transcription networks. By reversing the activation thresholds (K) of X and Y, a FIFO order is achieved in protein production, a just-in-time manufacturing sequence. See diagram below.

Like all feed-forward loops, the network embeds other valuable information processing. Each of the output nodes has a sign-sensitive input filter, ignoring intermittent absence of the X signal and noise from a fluctuating environment. Deactivation only occurs when X has been off for about the time period of one cell generation, the time needed to complete assembly of the flagellar motor. See more examples of network topologies and benefits below.

The author proposes convergent evolution across many information networks, from genes to protein kinase cascades, to neurons, which is quite plausible.

The premise that I wrestle with is his claim that these networks are readily understandable. Working from the bottom up, and from the incredibly sparse networks and topologies, I can see why he’s excited. But I wonder if this scales. Jumping to neuronal circuits, the easy modularity is a bit more elusive, and I wonder if the simplified networks of parasitic organisms are a simple tier in the hierarchy of abstractions, just a few steps more complex than codon encoding and epigenetics. Perhaps evolved information networks embed much more accumulated computational complexity and offer fewer pattern matches to our engineered artifacts.

The information systems of biology have so many interesting lessons on robustness and distributed action. Here is a fascinating talk on bacterial communication (chemical quorum sensing and nanowires).

12 responses to “Love the Bug”

  1. Schematic of the multi-output FFL that regulates the flagella genes:Picture 1The final product, motors on demand:Picture 2Features of common network motifs in sensory transcription networks:Picture 3That last one is also a common motif in neural networks, as it can embed fairly complex computations.

  2. This is very interesting. I have heard that IBM is looking into growing algae to make biochips. I find this fascinating.

  3. The information in the spatial relationships between members of the network is also quite important. Cells don’t just hang out planktonically in sterile saline.

  4. great to see them profiled. I went to their lab opening in Y2E2

    Todd – yes… making bioreactor scaling an interesting exercise in surface area vs volume… and probably a whole lot more to be discovered.

  5. the diagrams of the flagella bring back memories of the dover intelligent design trial:)

    i also just came across this today about e.coli used as bacterial computers…

    http://www.sciencedaily.com/releases/2009/07/090723194321.htm

  6. One of the most disconcerting aspects of bacterial (and yeast) life is behavior patterns that span cell generations.

  7. 10 trillion "45nm wide, 100 Hz proton-pump rotary motors" power the new TeslaGella from 0-100 kph in 2 seconds!

  8. Aw heck, at that scale, add a little intelligent design and go 100 GhzGustavoG: what are some examples of transgenerational learning (other than differential selection of mutants)? Population gradients? Quorum oscillators?

    Eppie: some deep questions there (in your longest paragraph) and some references that ring familiar… it’s the question that drives us. So much to learn, but at an accelerating pace…

  9. Epp – Yes! To all. When you add a few more data points to an exponential graph, the illusory "knee" of the curve shifts, and most of the past fades to static irrelevance.

    And we are reengineering the information systems of biology. More powerful yet, we are designing for directed evolvability.

    Speaking of engineering life, the results of the International Genetically Engineered Machines (IGEM) competition are in, and under Drew Endy’s direction, Stanford took the gold in the health/medicine category. Woot!

    See 2009.igem.org/Team:Stanford

    Lots of info in the red bar of links. Check out the maps and process…

    Professor Christopher Anderson at the University of California Berkeley commented: "This is, by far, the best use of synthetic biology as a therapeutic device that I have seen in a very long time."

    And it’s being done by teenagers.

  10. Just came across a number of interesting analogs between bacteria and cancer (signaling and motility triggers) with hints at better treatments. See last paragraph here.

  11. [in response to deleted comment] — sure. I was referring to this, the last paragraph of the caption:

    • Athena Aktipis’s tantalizing comparisons of conserved evolutionary homologs in cancer and microbial consortia. “Tumor growth is less of a problem than metastases spreading throughout the body and deregulating various systems. The mechanism of death is not really known in cancer research.” “All cells are connected to their neighbors, and then they disperse. When their consumption rate becomes a resource limitation, they follow a gradient to greater resources.” (this sounded exactly like a description of E.Coli, which I marveled at on this post). Given the convergent evolution across many information networks (from genes to protein kinase cascades, to neurons), I had to ask about Bonnie Bassler’s work hijacking the quorum sensing communication channels between bacteria — not to kill the bacteria, which induces evolutionary resistance — but to fool them with “counter intelligence” signaling so they happily live on without flipping into virulent mode. “Yes,” she said “To treat cancer, we could resolve the resource dilemma at the cellular level and, paradoxically, feed the tumor. Our goal should be to prolong life, not kill cancer.”

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