Until today, 13.628 biobrick sequences ⁽¹⁾ have been submitted to partsregistry, thereof 102 reporter units, 12 signaling bricks and xx sensing parts. Since there, people are trying to arrange these single biological building blocks in such a manner that allows producing special biotechnological products (metabolic engineering), developing biological sensory circuits (biosensors) and even giving microorganisms the ability to react on multiple environmental factors and serve both as disease indicator and drug. These examples and further promising ideas were implemented on previous iGEM-competitions.^(2)(3)(4)

The idea of combining these developed concepts to construct complex synthetic biological systems (e.g. by using several sensors from different iGEM-teams with the output of a third team) falls at the last hurdle - the fact, that each systems is based on a separate principle how to access and functionally connect the respectively used biobricks. In order to realize the full potential of these promising projects, our vision is to develop an adapter that allows interconnecting any arbitrary biobrick on a functional level. For developing such a system the adapter has to meet the following requirements:
beeing

• universal (fitting to each biobrick)
• extendable (numerous biobricks can be coupled in parallel)
• biologically orthogonal (allows creating a synthetic network without falling back to cell intrinsic ones)
• logical (one single unit can be coupled to perform operations like AND/OR/NOT)

Several biological logic units, devices and circuits have been developed so far⁽⁵⁾, but to our knowledge, none of them provides the opportunity to be a universal smallest unit like a transistor is in computational science. We investigated several hypothetically principles, and decided to focus our practical work on the development of a RNA-RNA interaction-based transistor by implementing two approaches:

• Designing a synthetic version of a RNA-sensitive riboswitch, which is based on the principle of shifting between a state of antitermination and termination as observed for attenuator operons in nature.[[Jump to coli-schalter| ]]
• Coupling this principle to the phenomenon of tiny abortive RNA´s, which cause antitermination in T7-termintors.[[Jump to t7-schalter| ]]

Both systems have to be tested for their ability of switching between termination and antitermination only in the presence of a signal. Therefore, our switches are generally divided into a switching unit, which is responsible for the functional shift between termination and antitermination, and a recognition unit, detecting the presence of a signal and defining specificity of our switch.

Although classical molecular biology and genetic engineering equipped the science community with many functional proteins and possible applications, using and linking different parts together to a working network still requires highly complicated strategies. The switches established in molecular biology, for example the lac operon, are highly limited, as most of them rely on interactions including metabolites and proteins providing only one on/off-signal. Thus, it is hardly possible to build up a logic network inside a cell without interferences between different switches. Our approach is to change this by developing a new and more robust way to control E. coli cells using RNA-RNA-interaction based switches, which we call bioLOGICS.
These switches allow an easy construction of networks consisting of AND/OR circuits. The major advantage of our RNA-based units is the possiblility to easily upscale and to include parameters for tailored protein expression control.
This is a major advantage towards ribozyme and especially protein based networks. While the complexicity of protein-protein interactions may work for cells, constructing networks without just copying complete operons is hardly possible. With the small size of our bioLOGICS, ten logic units occupy the space of an average protein sequence on a plasmid. Circuits based on bioLOGICS may play a key role for gene regulation with more variations than just on/off in the future.