Bioengineering from Parts to Devices
Kristian Müller, Potsdam University, Germany

Basic biotechnology such as beer brewing and dog breeding dates back to the early settlements of mankind. More recently genetic engineering was introduced enabling the systematic manipulation of metabolic pathways and breeding for defined genetic elements. The technology started with single genes and proteins and currently is routine for defined pathways and groups of proteins. As a next step, synthetic biology aspires to span the whole range from single components to complete cells and even organisms by providing an umbrella term and interdisciplinary platform spanning e.g. gene synthesis, biochemistry, genetic engineering, systems biology, (bio-)mathematics, (bio-)informatics, and abstracted circuit engineering.

In the context of synthetic biology, we work on the optimization of biological parts and the bottom up design of biological devices. At the part level, we apply rational design, directed evolution, and selections systems to optimize protein stability as well as to identify and manipulate protein-protein interactions.
At the device level, we improve and invent the enabling evolution and selection techniques. Examples are the use of a natural protein folding control mechanism in bacteria, a system in which an enzyme mediating cell survival is split and reconstituted, and modified phages. We also combine these systems to simultaneously select for various traits.

The second application area is the targeting of eukaryotic cells and tumor therapy. We analyze nano patterning on folded DNA-structures (DNA origami) as an interface to cells. More advanced towards therapy is a virus like particle approach for which we developed a mix and match toolkit. We use a small virus for which all production information can be provided on artificial plasmids and the genome can be replaced by genes of our choice. Using protein fusions or loop insertions we can modify the surface of the virus particle for easy purification and tumor targeting. The virus particle then acts as a shuttle for genes expressing enzymes which mediate cell killing upon delivery of an external prodrug.

Synthetic Biology encompasses also ethical, political and educational topics. For hands-on education for students, we took part in the international Genetically Engineered Machine (iGEM) competition. We conducted polls with laymen in various countries as well as members of the German parliament and we collaborated with philosophers to accompany the move from manipulation to creation.

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