Team:TU Munich/Project

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= Work Progress =
= Work Progress =
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Every network starts with a basic unit. While our declared aim is to enable networks allowing fine-tuning of gene expression beyond the regular on/off the first tests starts with exploring such an on/off switch/signal pair. We tested its efficiency, robustness and reproducibility ''in vivo'', ''in vitro'' and ''in silico''. Furthermore we developed a software which allows easy constructions of networks delivering a ready network.  
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Every network starts with a basic unit. While our declared aim is to enable networks allowing fine-tuning of gene expression beyond the regular on/off, exploring such an on/off switch/signal pair is the first step towards a functional network. We constructed several units and tested their efficiency, robustness and reproducibility ''in vivo'', ''in vitro'' and ''in silico''. Furthermore we developed a software which allows easy constructions of networks delivering a ready network. Conclusive elaboration of a few first RNA-based logic units is the major contribution of our iGEM team.  
<!-- The idea behind our project is to change the way BioBricks have been used up to now. Over the years, many receptors and signals have been constructed as BioBricks during the annual iGEM competition, but still it is not possible to interconnect these Bricks in a complex biological network resuting in a cell, that is able to respond to its environment giving differenciated responses depending on the input signals. (Beispiel: cambridge hat das gemacht, xx dies, aber eine zelle kann nicht beides...<br>
<!-- The idea behind our project is to change the way BioBricks have been used up to now. Over the years, many receptors and signals have been constructed as BioBricks during the annual iGEM competition, but still it is not possible to interconnect these Bricks in a complex biological network resuting in a cell, that is able to respond to its environment giving differenciated responses depending on the input signals. (Beispiel: cambridge hat das gemacht, xx dies, aber eine zelle kann nicht beides...<br>
We plan to create biological switches, that can function as locial gates inside a cell. Our switches rely on RNA/RNA-interactions, regulating transcriptional termination. This is a major advance of our concept, as regular switches rely on complex regulation including proteins and/or metabolites. Thus, our switches shall offer a greater robustness and their behaviour should be easier to predict. [[switch|Read more]] (hier sollte noch das hochskalieren erwähnt werden...<br>
We plan to create biological switches, that can function as locial gates inside a cell. Our switches rely on RNA/RNA-interactions, regulating transcriptional termination. This is a major advance of our concept, as regular switches rely on complex regulation including proteins and/or metabolites. Thus, our switches shall offer a greater robustness and their behaviour should be easier to predict. [[switch|Read more]] (hier sollte noch das hochskalieren erwähnt werden...<br>
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These switches can further be used to build up a logical network inside a bacterial cell, enabling every scientist to connect as many functionalities (in form of BioBricks) as designated. We plan to offer simulation on each specifically designed network.
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These switches can further be used to build up a logical network inside a bacterial cell, enabling every scientist to connect as many functionalities (in form of BioBricks) as designated. We plan to offer simulation on each specifically designed network.
<br><br>Over the years, many teams participating in the iGEM competition spent their time on constructing receptors and systems to detect a certain input that a variety of gorgeous oppurtunities is available so far.[[Image:TUM2010 network.png|thumb|300 px|right|Our visioon: A logic network inside the cell]] Nevertheless, until now it is not possible to link all those functionalities and build up a network giving differenciated responses to several of those input signals, where the molecular response depends on the complex composition of the environment a cell faces. We would like to offer this possibility to everyone.
<br><br>Over the years, many teams participating in the iGEM competition spent their time on constructing receptors and systems to detect a certain input that a variety of gorgeous oppurtunities is available so far.[[Image:TUM2010 network.png|thumb|300 px|right|Our visioon: A logic network inside the cell]] Nevertheless, until now it is not possible to link all those functionalities and build up a network giving differenciated responses to several of those input signals, where the molecular response depends on the complex composition of the environment a cell faces. We would like to offer this possibility to everyone.

Revision as of 19:46, 8 October 2010

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bioLOGICS: Logical RNA-Devices Enabling BioBrick-Network Formation



Vision

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.

Concept

The basic principle of our switches are short RNA sequences, the scientific idea shares similiarities with the principle of antitermination but also inherits a completely new way of RNA based transcription regulation. We used three-dimensional structure predictions and thermodynamic calculation to develop a set of switches - about 50 nucleotides - and signals - about 20 nucleotides. The switch forms a stem loop causing transcription termination, which can be resolved upon binding of a signal. On/off switching can therefore be easily controlled by signal avaiability and provides a new concept to control gene transcription. Read more

Network construction

Designing complex biological networks based on either traditional protein engineering or our new bioLOGICS is still a complex task. We developed a software which allows the fast construction of a bioLOGICS based networks.

Work Progress

Every network starts with a basic unit. While our declared aim is to enable networks allowing fine-tuning of gene expression beyond the regular on/off, exploring such an on/off switch/signal pair is the first step towards a functional network. We constructed several units and tested their efficiency, robustness and reproducibility in vivo, in vitro and in silico. Furthermore we developed a software which allows easy constructions of networks delivering a ready network. Conclusive elaboration of a few first RNA-based logic units is the major contribution of our iGEM team.



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