Our experimental research group explores the physicochemical properties of natural and artificial biomolecular systems and their potential applications in nanotechnology and synthetic biology.
Self-organization and self-assembly
On an abstract level, our main interest is the understanding and utilization of self-organization phenomena for synthetic applications. One aspect of self-organization is the self-assembly of molecular structures from small, interacting building blocks. The main characteristics of self-assembly is the generation of a structure on a large scale from only local interactions between these building blocks - they have no knowledge of the whole structure, and they are typically not guided externally. DNA happens to be a good molecular material to explore self-assembly phenomena, as it allows to tailor the interactions between molecules using a "code". Thus DNA self-assembly essentially is the "programming" of the sequences of a collection of DNA molecules to generate a target structure as their minimum free energy state.
However, the phenomenon of self-organization is much broader and in many ways more interesting than pure self-assembly. In particular, it also encompasses dynamic, non-linear and out-of-equilibrium phenomena - for instance chemical oscillations, waves, or pattern formation. Interacting components with internal structure (i.e., "states" and "state transitions") - which could be "nanorobots" or cells - can generate even more complex behaviors such as swarming. Again, using the DNA (or RNA) code one can program chemical reaction circuits with interesting dynamics and information processing capabilites, and thus attempt to generate and control more complex self-organization behaviors.
DNA nanotechnology: nucleic acid based machines and devices
DNA and RNA molecules can fold into a variety of different structures and shapes. For instance, complementary DNA molecules can bind with each other to form double-stranded molecules; self-complementary sequences can fold back to form hairpin loops, etc. It is possible to design molecular structures which can be reversibly switched between several alternative structures, some of which may have a particular function. Such switchable structures can find use as mechanical actuators, motors, sensors and even computational elements.
Chemical reaction networks and molecular circuits
Biochemical processes such as DNA hybridization, enzymatic catalysis, or gene transcription can be exploited to implement biomolecular analogues of electronic logic circuits and signal processing. For instance, the production or release of certain biomolecules can be made dependent on the evaluation of "diagnostic" computational rules. The realization of artificial biochemical circuits holds great promise for the development of advanced biosensors, but also for re-programming of biological systems in synthetic biology.
Artificial cell-scale compartments and reactors
Compartmentalization and spatial organization is one of the most distinctive features of biological cells that differentiates them from standard chemical systems "in a beaker". We are currently quite interested in the consequences of compartmentalization for the behavior of artificial biochemical reaction networks and systems. As cell-scale reactors, we typically utilize water-in-oil emulsiond droplets (which can be generated in large numbers in microfluidics) or lipid bilayer vesicles (which are closer to biological compartments enclosed by membranes). Among the many interesting features that can be studied is the occurrence of strong variations from droplet to droplet, which are caused by statistical fluctuations at small molecule numbers. Research on cell-scale systems is of interest both from a technological and a fundamental point of view. On the one hand the systems are useful as microcontainers for biotechnology, in vitro synthetic biology and screening applications, on the other they can serve as primitive models for cells ("protocells").
Synthetic biology is the "engineering of biology". Apart from the many potential applications envisioned for synthetic biology, it also poses a series of fundamentally interesting questions. As biological systems are inherently complex (which means: many strongly connected, interacting components, nonlinear, out-of-equilibrium) - the idea of synthetic biology essentially represnts the challenge of engineering of a complex system. In this context, we are particularly interested in the exact quantitation of the behavior of biological systems (in particular gene circuits), and the development of robust and orthogonal design strategies. Furthermore, synthetic biology allows us to deliberately alter biological systems in order to address specific biophysical questions (very much like traditional experimental physicists design an experiment to test a physical theory).
Biomolecular hybrid systems
The unique biophysical and biochemical properties of DNA molecules can be utilized for the construction and assembly of artificial biomolecular nanostructures. Due to the intimate linkage between DNA sequence and structure, DNA is ideally suited as a material for "programmable" self-assembly. Recently, the field has been revolutionized by the introduction of the "DNA origami" technique which allows for the realization of almost arbitrary two-dimensional and three-dimensional shapes. Our group currently explores its use in the context of biophysics and bionanotechnology