Endy:Writing:CCfGDThoughts

Right now this thing reads to me like it was written for scientists who are already 75% of the way there in their understanding of the subject - so why would they want to get the last bit of knowledge from a comic? The project gets a lot more interesting to me if we're explaining what's going on from the ground up to a clueless guy on the street. In that case, taking a cartoon form makes more and more sense. Er...Hold on - maybe it's just missing one essential piece to make it meaningful: so now they've got a common signal carrier - so what? The strip needs context. What can they do with a common signal carrier? How is it applied in building life? Are those questions too big to be answered here?

The story was definitely designed (without thinking) for somebody who already knows what an engineered genetic device is (e.g., an inverter) and even a genetic system (e.g., a ring oscillator), but who does not understand the theory of how to design genetic devices so that they can be easily combined into systems. This has been a major sticking point for us in teaching and disseminating our ideas across the research community. Everybody is *so* used to thinking about the "state" of the cell as being defined by the levels of proteins and stuff, but you're screwed if you use individual protein levels as your device signal carrier (b/c then you can't hook the devices up in combination with one another -- it would be like if every electrical outlet in your house provided a different sort of electricity... grape electricity, apple electricity, banana electricity, and so on... ). So, the big picture context of the strip would be that we are trying to communicate the invention of this thing called PoPS, which is the equivalent of having a common "electrical current" for gene expression/for DNA. The "so what" is that once you have your common signal carrier, you can hook every device you make to every other device. This means that you can make really complicated stuff quickly. For whatever reason, in our classes, it takes us a painful ~two weeks to teach this one idea. It feels like it should only take ~15 minutes. I was naively hopeful that a comic could help bring to life the sticking points in thinking about PoPS, such that somebody could chill out and mull over each of the issues.

To extend the above to the person on the street, feels like we'd need to include a two-part preface. The first part might be about "programming DNA" and why that matters/is cool. The second part might be about how you program DNA to make devices (e.g., an inverter). At least this second part I was thinking might be a good supplementary panel (but I really don't know how to think about this in the context of a comic... do you ever use extra endnote or footnote panels?)

The biggest challenge - what the entire thing could hinge upon - is finding some good visual analogies to work with. A bunch of labeled boxes and charts are going to get dull real fast. What are we talking about? Proteins? Don't proteins have some kind of visual component? "A protein switching from A to B is like a caterpillar turning into a butterfly" - something! Even comparing it to electronic components is more interesting.

Good point. So, the way one of these (PoPS-based) inverters works (in the high input/low output setting) is that (1) gene expression in the form of a molecule of RNA polymerase comes racing in the front. This might be visualized as a "steam engine-like blob" trundling along DNA rails Then, as a result, (2) a protein's concentrations shoots up. This might be visualized as some protein blob taking flight (getting launched up), or pressure building up, liquid filling a tank, lots of possibilities here. Next, (3), the protein from (2) *slams down* onto the "operator site" (which is the output terminal for the inverter device). This prevents new molecules of RNA polymerase from firing up and racing out from the end of the device. Depending on how (2) is depicted, this inhibition of output might involve the protein blob from (2), having taken flight, landing down on the output terminal and squatting, thereby blocking the PoPS output signal from getting going (i.e., no racing steam engine-like blob leaving the device).