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Understanding DNA Motif Distribution: A Learning-by-Building Approach

Building blocks DNA

Torsten Waldminghaus spoke to us about his thoughts on the work of the Craig Venter Group and Jeff Boeke, the stigma attached to synthetic biology and his own work building synthetic secondary chromosomes.

What aspects of synthetic biology do you focus on?

My group is interested in the general question of what it is that makes a chromosome be a chromosome. There is certainly more to it than just the genes. All organisms need so called chromosome maintenance systems that facilitate folding, segregation, replication and repair of the chromosomes. In bacteria, many such systems are based on specific DNA motifs which are bound specifically by proteins to carry out a respective chromosome maintenance function. We take a learning-by-building approach to understand the relevance of the respective motif distribution on the chromosome. To this end we have designed and constructed the secondary synthetic chromosome synVicII. It replicates an extra small chromosome in the model bacterium Escherichia coli and can be used as an experimental chromosome. You can, for example, construct a set of synVicIIs with different distributions of your DNA motif of interest and see what happens to processes such as segregation or DNA repair.

Does that mean you construct chromosomes just to answer your scientific question?

Yes, absolutely. The secondary synthetic chromosomes contain no genes besides those needed for its replication because we want to exclude interference from gene functions. The synVicIIs we construct at the moment are about 100,000 bp in size. We have developed a quite fast and relatively cheap assembly pipeline so that students are able to construct synthetic secondary chromosomes in their Masters projects.

Where does the name synVicII come from?

The difficulty lay in how to get a secondary chromosome when most bacteria have only a single chromosome. One well studied exception is Vibrio cholerae, the causative agent of the cholera disease. So we borrowed the replication origin and the respective genes that activate it from Vibrio cholerae and based our synthetic secondary chromosome in E. coli on it. So the name “synVicII” means something like “synthetic chromosome based on Vibrio cholerae chromosome II”.

What do you think of other synthetic chromosome projects such as the Mycoplasma work of the Craig Venter group or the synthetic yeast chromosomes of Jeff Boeke?

I think their pioneering work is fantastic and many more people should start constructing synthetic chromosomes. All of us have different ideas and interests and it is important to build chromosomes based on various designs. There is probably an infinite number of possible chromosome designs so the young scientists in the field need not to worry that they will not get a cool synthetic-chromosome project.

What do you think of the idea that synthetic biologists are playing God?

I understand that people are wondering about where the new synthetic biology approaches could lead us and think it is important to get the public involved in discussing what we want and what we don’t want to do with it. At the SYNMIKRO Center for Synthetic Biology, where I work, we have a group of people, headed by a colleague from theology, for the discussion of bioethical issues related to synthetic biology. For myself, I could say that synthesizing chromosomes and looking at nature from an engineering point of view increases my fascination of how great nature is. Albert Einstein put it this way: “The more I do science, the more I believe in God”. Today this can be adapted to “The more I construct chromosomes, the more I believe in God”.

Prof. Thorsten Waldminghaus
Torsten Waldminghaus
is Professor for Synthetic Biology at LOEWEcenter for Synthetic Biology and Philipps-Universität Marburg. He will be speaking at the 3rd Synthetic Biology Congress.

To see who else will be speaking at the Congress, view the full agenda here

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