Team:Grenoble/Project/Overview

From 2012.igem.org

iGEM Grenoble 2012

Project

Overview

Our DeviceOur Safety project

During the past thirty years the world has been at peace but tomorrow will be different. Since the invention of antibiotics, mankind has been over-using and misusing them to cure diseases. And we are on the edge of paying the bill back. Since the discovery of antibiotics and their use in medecin, we have seen the emergence of resistance in bacteria. Recent years have witnessed the propagation of these resistant strain; making the treatment using antibiotics less and less efficient.
Today, certain strains of bacteria are resistant to several antibiotics; making the treatment process difficult and threatening patients' life expectancy; especially in the case of severe infections. In the case of severe infections, physicians have to set up a treatment as quickly as possible. In a first place they use broad spectra antibiotics (less efficient but they act on several strains). When the identification of the bacterium is done (and if the patient is still alive) they use an antibiotic specific to the identified strain [1] [2].

Several governments are taking measurements against the spreading of these Multi-resistant Bacteria (MRB); by limiting cross contamination in hospitals or by reducing the selection pressure on microorganisms (limiting antibiotic treatments). These measurements are often expensive to set up and are not 100% efficient.

A way to limit the contamination would be to systematically screen each patient. However, this would be very expensive (check out our cost assessment) and the public health system can simply not afford this kind of expense .

This year iGEM 2012 Grenoble team brings Synthetic Biology to a whole new level.

Our Device:

We developed a synthetic biology project to use engineered bacteria as low-cost, reliable, sensors possibly adaptable to many different pathogens. We worked on three modules to create our device: detection, amplification and communication between bacteria.

Detection:

The team built the membrane receptor to perform the detection. It consists of the assembly of two protein domains: the external part comes from the Tap protein, a receptor involved in chemotaxis, and the internal part comes from the EnvZ protein, which is the sensory histidine kinase of the EnvZ/OmpR two-component system. The receptor is not directly activated by the pathogen; but by the protease produce by the pathogen which will cut a designed membrane protein; releasing a dipeptide which will be detected by our designed membrane receptor.

Amplification:

The team designed a new biobrick which provides the appropriate amplification characteristics to our system (amplification and noise filter). The amplification is achieved thanks to a positive loop. The noise filtering is achieved thanks to a well known promoter which we used in brend new way. Indeed, we used the pAra/Bad promoter from E. coli as an AND gate. We tested this new AND gate (take a look at our results).

Communication:

In order to improve the strength of the output signal, we used a natural communication system present in E. Coli which allow bacteria to communicate using 3'-5'-cyclic Adenosine MonoPhosphate (cAMP) (our friend's PhD thesis).

Our Safety project:

During the summer, we worked on the risks with biological experiments: More precisely we focused on the risks linked to UV radiation, chemicals and biology. For the two first, we succeeded in reducing the exposition of the team members and further users of the laboratory. This was achieved thanks to the addition of safety measurments adapted to the experiments.

We focused our work on the biological risk. Synthetic Biology is an emerging activity and even if the current method to evaluate the biological risks does not reveal any risk, this does not mean synthetic biology is safe of use. Some feedbacks about Genetically Modified Organisms (GMO) used in different fields have shown drawbacks (e.g. Transgenic corn).

Since the first iGEM competition the number of teams has been increasing; and because we think that it will continue, we tried to develop a way to store team feedbacks (experiements and observations) on the use of biobricks. However, we developed a prototype which is why we asked for feedbacks from other teams (Edinburg, Gröningen, Paris Bettencourt and Virginia) to improve its structure and content.

The result is a BioBrick Safety Sheets; this project could really improve the structuring of the information, but a work was done to link it with the current registry of standard biological parts. In the future, if this structure is used this would lead to the creation of a software that would contain every interactions for each BioBrick. This is the way we participate on the improvement of the safety in Synthetic Biology.

In the future, we hope that this safety sheet will be implemented in the part registry and be linked with software which would be accessible online (like the NCBI Database).

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