Follow-Through in Synthetic Biology Research

I have just read a pair of papers, both of which outline theoretical methods of creating synchronised oscillation circuits in bacterial cells.
Synchronising Genetic Relaxation Oscillators by Intercell Signalling
Modelling a Synthetic Multicellular Clock: Repressilators Coupled by Quorum Sensing

In essence, the idea is to make bacteria who “blink” as whole colonies, by creating and destroying a fluorescent protein in an on-off manner at the same time as a group.

This has been done in single cells, but as you might imagine the pattern of on-off gets lost in the crowd of a whole colony of millions, so the effect isn’t clear to the naked eye. The importance of the research cannot be understated; if synthetic biology is going to be the next revolution in technology (and it is), it will need to be based on a platform of genetic systems that can be adapted to engineering goals. Having a system that can offer a timed, predictable output is essential.

Basically, the computer processor that drives the device you are using to read this is utterly dependent on a “clock”, the speed of which is often used to sell the computer or device in question (New processor! 84GHz! Buy Now!). Biology has no such “clock” yet with which to synchronise the actions of engineered cells, and these papers suggest ways of doing so.

The problem is, both papers only offer mathematical models of their systems, even though they have fully detailed the genetic basis behind them. For the latter paper, I have calculated the cost of creating the engineered bacteria they describe using Gene Synthesis, based on the sizes of the proteins they describe in the paper plus 20% to cover regulatory regions and cloning sites necessary to construct the system in question. I assumed a cost of €0.30 per nucleotide of DNA, consistent with the current price from

So that’s the three repressors, LacI, TetR and cI, plus the Lux proteins LuxI and LuxR. The links lead to their articles on Uniprot; the relevant datum is the number of amino acids, each of which corresponds to three nucleotides of required DNA. The added 20% is the number of nucleotides I expect would be added to cover restriction sites at either end of each ordered sequence, plus promoter sequences to make the researcher’s job one of simple assembly.
The tally? Only €1347.

Now, that may be significant money to an individual, but frankly if I’d designed that system to an extent that I would be comfortable writing a paper about it, I’d feel stupid not to order the DNA and prove my hypothesis. To have the world’s first independently synchronous bacterial clock, which sat there on a petri dish and blinked at me every few minutes? Not only would it be satisfying, it would be newsworthy and game changing. And it would add a ton of weight to the published result, rather than a slew of mathematically modelled predictions. In other words, it would be seriously awesome stuff for your career, a solid investment (better than a TV anyway!)

That’s €1,347 of money that the authors of the latter paper (not to mention the first, which might have been cheaper) never spent.. but why? Because testing their hypothesis could have disproven it? Even a negative result adds to the body of knowledge in such a young field.

I’m frankly pretty amazed. In my research on oscillators, I’ve seen a few but none yet that have used quorum sensing to synchronise cells, even though two papers have been written on the topic with favourable predictions of worth. Considering the cost (compare this to the cost of the Craig Venter Institute’s basic copying of an existing bacterial genome, a staggeringly expensive task which ultimately added little to the body of knowledge on the topic), this lack of follow through is confusing. Especially since this is clearly the field of choice for the authors: some of their publications since that paper have been equally exciting.

If they’re not going to do it, I will. As soon as I have a lab capable of creating transgenic bugs and enough money to throw at it, I’ll feel compelled to make the world’s first blinking bug. Who knew there was such low-hanging fruit awaiting a fresh synthetic biologist? Anyone feel like helping me bootstrap ASAP, and getting a free blinking bug as a prize? ;)