Team:UQ-Australia/Modeling

Bacterial killers from a genetic construction kit

Under supervision of Prof. Dr. Roland Eils, a team of undergraduate students develops a biological machine that can detect and kill pathogens or even cancer cells – 84 teams from all over the world participate in the Synthetic Biology iGEM competition.

iGEM (international Genetically Engineered Machines Competition) is a competition organized by MIT (Massachusetts Institute of Technology) in Boston, USA, since 2005 and has become one of the largest international competitions in the field of science. This year 84 teams of undergraduate students compete against each other, and for the first time three teams from Germany join the competition. The project of the Heidelberg team is directed by Prof. Dr. Roland Eils from University of Heidelberg and the German Cancer Research Center (DKFZ).

Synthetic Biology is a young field in science, which combines classic gene technology with an engineering approach. Similar to the construction of an airplane, Synthetic Biology uses simple gene building blocks for the construction of new complex systems with distinct functions. These gene building blocks are collected in a database by iGEM and can be used by all participants of the competition. So far, the collection contains more than 1000 gene building blocks, due to the continuous development of new parts over the last years. This summer all teams work on self-developed projects which will then be presented in the beginning of November at the “Jamboree” in Boston. Several prizes in different categories will be awarded.

The Heidelberg team consists of 15 students of the University of Heidelberg and one student of the TU Darmstadt, all with a different scientific background including Molecular Biotechnology, Biology and Mathematics. The students are supported by advisors from the group of Victor Sourjik (ZMBH; University of Heidelberg) and from the division of Roland Eils (University of Heidelberg and DKFZ). The project itself is carried out in the newly founded Bioquant building, a center for qualitative analysis of molecular and cellular biological systems.

The Heidelberg team is developing a biological machine that is able to detect and specifically kill pathogens or even cancer cells. In a proof of principle study the team has genetically reengineered two E.coli strains into a prey and a killer strain.

The system consists of two modules: a module for the recognition of the pathogen-presenting prey cell by the killer strain, and a module for directed movement of the killer cells towards their prey. The team utilizes the natural sensing and movement system of E. coli bacteria, which in nature is used to sense nutrients, by redesigning the receptors of the killer strain to sense a molecular cocktail secreted by the prey strain.

After arriving at the prey, an additional gene module is activated which then leads to the death of the pathogen or the cancer cell. The Heidelberg team follows two different strategies to achieve the killing. The first strategy focuses on bacterial toxins, the other one uses viruses specific for bacteria. Toxins are normally produced by certain bacterial strains to kill other bacteria. However, these toxins are also able to kill cancer cells, making this approach possibly suitable for the elimination of cancer cells. For the test system the team uses genetic information of bacterial toxin production. This information will be introduced into the killer-cells and modified to only become active once the killer strain reaches the prey strain. Activation then leads to toxin production and release, finally resulting in killing of the prey-cell.

The second approach for killing the prey uses bacterial viruses, which naturally infect E. coli cells. During infection the phage inject its genetic information into the bacterium, forcing it to produce new phages, which are released afterwards. Free phages are then again able to attack other bacteria. In this approach the team specifically takes advantage of the domino effect, which allows killing a high number of prey cells with only a few killer cells.

In addition to the experimental work in the laboratory, an important part of the work involves computational modeling of both the sensing and killing module. The model simulations allow the prediction of system behavior under various conditions and help to better design the experimental work.

The Heidelberg team is in the middle of its project work. The students are working day and night for three months on this ambitious project. Initial results have been achieved for both the experimental and the modeling parts. The team aims to accomplish its project goals by the jamboree competition in early November at MIT in Boston and to thus compete with international teams from renowned places such as Harvard, Cambridge and Tokyo.

News

29 Oct. 2008, Wiki-Freeze culminates into iGEM Ecolicence Song

To see our spontaneous iGEM Ecolicence composition click here

28 Oct. 2008, Generous Donation by Klaus Tschira Foundation

The Klaus Tschira Foundation gGmbH is a non-profit organization and supports research in informatics, the natural sciences, and mathematics; at the same time it promotes a public understanding in these sciences. With this combination the Klaus Tschira foundation is our ideal partner in this competition.