138. Synthetic biology and iGem: part 2

This is the next (and probably the last – we will see ) part of my interview with Alexej Skvortsov, the leader of the Russian team in iGem 07, international competition in synthetic biology.

D.: How did you check that your bacteria have the properties you wanted (in your case, that the reaction to the copper abundance is present)?

A.S.: This problem (one of the simplest ones) is not yet solved, since we did not present the working example of bacteria yet. Several elements in the Registry of Standard Biological Parts may work as effective indicators – corresponding sequences of genes encode fluorescent proteins. If you put such an indicator into the contact with regulator and turn the latter on, bacteria will become (if you highlight them with blue light) red or green colored in several minutes. Here is an example of the genetic sequence encoding indicator – http://parts.mit.edu/registry/index.php/Part:BBa_I13521. Using spectral methods, it is  easy to determine how much of a given color is present in the sample.

D.: How DNA fragments (BioBricks) are created in practice? How rapidly can they be synthesized? who was responsible for the actual DNA synthesis in iGem – the teams themselves or somebody else?

A.S.: In practice, it is very simple if you have the necessary equipment and ferments. We perform the synthesis ourselves (this is what represents the educational part of the project), the team working on synthesis includes 3 and 6 year undergrads.

If one has to explain the process in a few words… First, we “implant” required genetic material into bacteria (this part of the process is called genetic transformation). The operation is rather rude w.r.t. bacteria – no more than 1/1000000-1/10000 of their initial population survive, but the positive part is that we have lots and lots of them Transformed bacteria divide and amount of the genetic material rapidly increases (this part of the process is called molecular cloning). Then, one is supposed to extract the resulting DNA from bacteria, cut the DNA by special ferments (that is where we got stuck because we were unable to receive all necessary ferments in time), mix it up with other fragments of genetic code and glue them together using other ferments.

The BioBrick standard proposed by the iGem host is especially good since all the fragments are glued together in the way they are supposed to with 99% probability. Unfortunately,  this is not always so in real scientific research and applications. Short sequences are actually synthesized by commercial companies. After the synthesis and appropriate “wrapping” they are ready for cloning in bacteria.

All these things are very well known (and the technology – established) from 1970s. I would like to recommend the Watson’s book “Recombinant DNA” (containing all the nesessary material at the level understandable for a beginner).

As for the characteristic time scale of the synthesis process, construction of a single sample takes about 5 days (the length of the process is essentially determined by the fact that bacteria population requires sufficient time to grow).

D.: In Russia, some serious investments into nanotechnology are currently planned. To which degree, can synthetic biology be considered as an alternative to nanotechnology? From your point of view, is it possible to build an equivalent of nanoindustry on the basis of synthetic biology?

A.S.: You know, I am rather sceptic about nanotechnology and its possible applications – in particular, since virtually nobody is able to accurately explain what is nanotechnology and nanoindustry. My favorite joke is: nanotechnology is from technology, all what remains is propaganda There are many popular speculations of a general character, but when one turns to real achievements and perspectives of nanotechnology, there are not so many. In this situation, all money-lovers turned into experts in nanoscience, got their grants and currently keep doing what they were doing before. Because of that, I think, money invested in nanotechnology in Russia will be slowly (or not so slowly) dissloved in space and time without any noticeable result produced.

Synthetic biology is also very young and not well established branch of science (by the way, there is no single serious research group in Russia working on  synthetic biology and its applications). However, its foundations related to genetic engineering, applied chemistry and bioinformatics seem much more solid to me.

From my point of view, the main advantage of artificial systems constructed by means of genetic engineering is that they use the natural life cycle, which is in harmony with the laws of thermodynamics (almost always forgotten by futurists lobbying nanotechnology). I think that is why the path of synthetic biology will more rapidly lead to some  practical applications. But this would be a good subject for a separate discussion.

D.: Would you like to give us a couple of comments regarding the project of Chinese team (who has won iGem 07)?

A.S.: The goal of the Chinese team was to construct bacteria able to differentiate – the title of their project was “Towards Self-differentiated Bacterial Assembly Line”. Differentiation is a process when initially homogeneous group of cells is separated (in space) into several groups of cells with very different properties. Differentiation is the necessary condition for the existence of any self-organization giving rise to a multicellular organism.

In bacteria, differentiation is a rather rare phenomenon (inherent to only some cianobacteria). Normal cells in E.coli are not differentiated, i.e., are all similar. This fact is not always convenient for biotechnology.

The Peking team has constructed two elements of the differentiation scheme that they have also proposed. Since the presentation is not uploaded to the iGem website (and I was not around during the Jamboree time), I am not sure whether they were able to actually construct differentiating cells.

Although the work of the Peking team was very good, I don’t feel that it was the most interesting. Personally, I liked the projects of the UC Berkeley team (artificial blood) and the team from Slovenia (by the way, the latter team is very strong – they were winners of  ’06 competition) more.

D.P.: Thank you very much for the interview.

A.S.: I would like to thank the D. Zimin’s fund “Dynasty” who supported our project.

Instead of conclusion

Note that the Nobel Prize 08 was given for fluorescent proteins Alexej has discussed a bit above. It is clear to me now,  why indicators have made a revolution in molecular biology and genetics.

Slovenia also won the ’08 iGem competition – indeed, the dream team. I would recommend you to take a closer look at the results table of iGem ’08: it does contain some surprises – in particular, US universities did not do that well in the competition. No russian team has participated in iGem this year. Sad, probably, too much is invested in nanotechnology.