At the iGEM Jamboree there was a lot of discussion of Minimal Cells, cells that have the fewest number of components to function as a laboratory organism. One of the key benefits is that it's a defined organism that does only what it needs to do and gets out of the way of the main things someone wants to use them for, say, to create an engineered machine.*
From the discussions, a few said that the route to a Minimal Cell was to subtract components from a current cell and see which ones were essential for operation.
That didn't sit well with me. And it took a while for me to develop an analogy to explain why.
To me, removing components from an existing cell to create a Minimal Cell is like removing components from a Boeing Dreamliner to see what's essential for an airplane (a Minimal Airplane could be like a Wright Flyer).
The mistake is forgetting that even bacteria are highly complex and evolved organisms with complex multi-subunit enzymes and structures. That complexity causes a limit to what can be removed, simply due to the complexity-overhead the bacteria has accumulated over billions of years.
In the plane analogy, the Dreamliner has a ton of essential components, say fly-by-wire, that really were added in evolution, replacing a simpler version, such as manual flying. The function, "controlling the flaps," is what's important, not the component. And the fly-by-wire system makes a whole load of other systems essential (complexity overhead), but which could be dispensed with in a manual system.
Makes sense?
I suppose I am of the school of bottom-up rather than top-down construction of Minimal Cells. And I suppose these discussions have already happened. [Indeed, Foster and Church's 2006 paper "Towards synthesis of a minimal cell" is a good foundation paper.]
I'm not trying to knock on all those working on Minimal Cells. here is a benefit to top-down reductionism, teaching us which pathways and functions are essential, even if we are not finding out the ideal components.
I'm just trying to develop a metaphor for myself to help me think of how to build a Minimal Cell.
That's all.
Image from Boeing
*Heh, one interesting thing I noticed at the iGEM Jamboree was a vocabulary developing around synthbio – machine, quorum sensing, chassis – words I've never used before in biology and that come from engineer-speak. I like it. 🙂
An interesting analogy, but then wouldn’t the bottom up approach in this case would be like trying to make a 747 without knowing how a jet engine works? I think the analogy also breaks down when you realize that we have all the “missing links” and the actual designs and blueprints for all airplane parts as they “evolved”, while in biology we’re starting with the dreamliner and trying to figure out how it’s “designed”
Also, would you even ride in a “minimal airplane”? The question isn’t as ridiculous as it sounds (I think); a minimal cell would almost by definition not include the redundancy and robustness that makes cells such interesting and useful “platforms” for synthetic biology and industrial biotechnology. The minimal cell is an interesting project for understanding how cells work and perhaps how they evolved, but I’m not sure how useful they will end up being compared to yeast or e. coli in industrial applications (at least not in the relatively short-term).
p.s. quorum sensing comes from microbiology, not engineering (at least I think so)!
Great post molecularist!
@Christina I think the bottom-up approach is more closely analogous to building a glider from scratch, rather than a 747, and learning about aerodynamics in the process before attempting to attach an engine.
@christina Thanks for the comment! Good point on the robustness and using minimal cells in industrial settings.
As for quroum – in my many years at the bench, I do not recall the term, though, yes, it probably comes microbiology. We just used to use other terms to describe that, mostly with eukaryotes (fungi, insect tissues, etc).
@james – thanks for the comment, too.