137. Synthetic biology and iGem: interview

This story is rather long one…

Browsing the web approximately a year ago , I have found an interesting article on wired.com which did show that biology students are considered somewhat more important asset than physics students nowadays – in particular, they are getting taught more effectively and more money is invested in their education  (the former, I guess, requires the latter, and yes, Ok, I am jealous )

If you decided not to click to the article in Wired, I’m talking about International (undergraduate!) student competition in synthetic biology iGem . First of all, what is synthetic biology?  Basically, today we know so much about how different micro-organisms (as well as their various parts) are functioning that we could try to engineer other, new, micro-organisms with properties that we want. The word “synthetic” in synthetic biology essentially means synthesis between biological science and engineering lore. Synthetic biology is a rather young actively developing (undeveloped?) branch of biology (the term itself was introduced in 1974) and without surprise it gets extremely popular among ambitious undergraduate and graduate students of faculties of biology, who want to make career in science as quickly and effectively as possible

As I said above, iGem is the international student competition in synthetic biology. Citing Wired,

The competition is a showcase for the burgeoning field of synthetic biology. Knight and his colleagues Randy Rettberg and Drew Endy, who created the contest in 2004, want to make biological systems easy to build by applying the tools of computer science and engineering: using standard parts and modular design to simplify complex systems. The goal is to create “genetic Legos” that could produce any chemical, from ethanol to pharmaceuticals.

In order to be accepted for the iGem competition, teams from different universities around the world were supposed to use the genetic repository at MIT (so called Registry of Standard Biological Parts) and construct a new genome of a bacteria having some interesting properties (maybe even useful in industry). For example, the team from UC Berkeley has created

… bacto-blood — an E. coli-hemoglobin mashup. The E. coli were engineered to produce hemoglobin – which carries oxygen to cells – and a chemical called trehalose. The trehalose made the cells able to withstand freeze-drying. Freeze-dried blood could come in handy in developing countries with limited refrigeration. It could be easily stored – just add (sterile) water when needed.

The idea of genetic Lego somewhat resembles Drexler’s nanobots with the only difference of the physical scale involved , so I immediately got interested in the subject and contacted the instructor of the Russian team in iGem 07 Alexej Skvortsov, associate professor in Biophysics Department, Faculty of Physics and Mechanics, St-Petersburg State Polytechnical University. He has kindly agreed to answer my naive questions about synthetic biology and iGem, see below (D. – me, A.S. – answers by Alexej). All mistakes you will find in the text are completely due to me being failure as a translator from Russian to English (the interview was initially conducted in Russian).

D.: What was the goal different teams at iGem have pursued -  did you have to present only a theoretical description of genome or was it necessary to construct real bacteria, i.e., represent “working” examples of the bacteria with required properties?

A.S.: To large degree, the iGem project is educational, i.e., its goal is to help team members to develop a better understanding of the principle of molecular genetics and methods of genetic engineering. In the ideal case, team was supposed to develop a theoretical basis for its project as well as to realize the project in practice. Thus, the answer to the question whether the given project is realizable played very important role.

According to the rules, we had to present our constructions in the BioBrick format and send them to the Registry in the form of DNA samples. Let me note that the Registry is more than just a website; in the beginning of the competition, every team receives a hard copy of the Registry, i.e., all the DNA samples you find on the website of the Registry. Each elementary block in the Registry is a DNA sequence in the form allowing its implantation into E.coli and subsequent reproduction. Presentation of a working example is very important and largely defines the outcome of the competition. Unfortunately, our team was unable to finish synthesis in time (June-October), because we did not receive ferments necessary for operations with DNA. We have bought ferments on summer, but have received only now, after the end of iGem – that is just a consequence of the fact that we are located in Russia. Nevertheless, now we are planning to construct developed details in the form of DNA.

Let me note that “genome” is an ensemble of all genes in a organism; our goal is much less ambitious than to deal with the whole genome, we are working with single genes having well-known properties. According to the synthetic biology concept, we do not need to know how are genes functioning and what is their fine structure; what we do need to know are their properties.

D.: How did your team develop your BioBrick? In particular, how did you figure out that a given DNA sequence is responsible for the detection of copper ions? (Alexej’s team has introduced a project of the bacteria which respond to high concentration of Copper ions in the medium.)

A.S.: To answer this question, I have to get into details of structure of a single gene. Any gene consists of promoter (defining whether the gene is turned on or off) and coding sequence (defining the outcome, the structure of the final product, for example, of a protein or a number of proteins). In bacteria, logic of gene organization is very precise, much more precise than, say, in mammals. In a sense, metabolism of bacteria is very close to perfect, and therefore it is much simpler to make genetic constructions in bacteria. One important feature of genes in bacteria is that promoter and coding sequence are not overlapped (as you remember, DNA is a long linear genetic text). As a result, it is possible to glue coding sequences of one genes and promoter parts of others (like in LEGO) in order to create new “genes”. I put parences here since the gene sequences were actually created by Nature, not by us. Our fragment  was represented by a single part from the Copper-dependent (at least supposed to be so) gene in E.coli.

Normally, this gene is activated (after a long sequence of events) when the concetration of copper ions in the medium grows. The gene also encodes pumping of copper ions away from the cell. We have found this genetic sequence from the NCBI open database analysing recent bibliography on effects of copper. We have supposed that the given sequence will activate any code that we substitute with the growth of copper concetration.

Let me also explain how we “cut” the sequence from the gene. Here a recent technological achievement has helped: DNA synthesis from the known sequence. You send te sequence (as a text) to a company, pay some money (in Russia – of the order of 1 EUR per single letter)  and receive the DNA sample in vitro. This is a common practice today – in a sense, it lays in the basis of synthetic biology – it is much more easier to synthesize short genetic sequences (less than 100 letters) rather than to cut them out of a DNA. iGem support team offers the DNA synthesis themselves, but it is of no use for us taking into account the delivery expenses.

To be continued.