Team:UQ-Australia/Project

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Overall project

Inspired by the circadian clock in humans which regulates a number of very important processes, we are trying to replicate this biological clock in a bacterial system. We are aiming to construct a network of genes that oscillates in a similar fashion to the 24 hour system in humans. If we are successful, we will be able to put different genes into our system so that we can make the bacteria perform a particular process periodically – a simple example of this would be to make them flash on and off consistently.


To achieve this oscillatory behaviour we will utilise a gene network with a series of inducible promoters that generate the production of other activating proteins, all driven by a constitutively active promoter. This promoter features an engineered repression domain (the inhibitor of this promoter being the output of the final step in the network). If everything goes as planned, these linked activations and repression will produce fluctuating levels of the proteins in question, which could then be used to drive our output function (initially just GFP production and a timed fluorescence). Ultimately, we hope our system could be used to drive the timed release of drugs or other biological factors.

Project Details

The project has been split into categories:

  • Development of BioBricks
    • Experimental methods to be fully recorded in the Notebook
  • Modelling of the circuit
    • Modelling of the kinetics of the oscillating cells
    • Modelling of the synchronisation of oscillating cells
  • Thorough evaluation of the safety issues regarding UQ-Autralia's entry in iGEM
  • Human practices
    • Raising awareness of synthetic biology
    • Providing a solution to the patenting issue that iGEM is facing

Together, this forms the UQ-Australia project for the 2011 iGEM.



Experimental Work

Modelling

At the completion of the experimental work, we should expect a working clock BioBrick, which should exhibit oscillatory behaviour. We wish to characterise how our clock BioBrick oscillates. Of interest is the frequency and regularity at which it oscillates and whether multiple cells containing our BioBrick oscillate in time with each other.

The modelling will involve the mathematical characterisation of the kinetics and synchronisation of the oscillation of our bacteria. The kinetics involve modelling how fast our bacteria cells will oscillate and the shape of their oscillation pattern. The synchronisation is to characterise how quickly nearby cells would couple any synchronise their oscillation.

To give a rough idea of how our cells should be oscillating, mathematical models were described from literature. These would ideally be compared with experimental characterisation of the oscillation.

Safety

Details of this is on the Safety page.


Human Practices

Outreach

Patenting

In a dynamic field such as synthetic biology, discovery moves at an astounding pace and is driven by the findings of groups from all around the world. However, conflict often arises when the choice between collaboration and commercialisation arises, and consequently patents have become commonplace in the scientific world. In the last 5 years, 34% of respondents had applied for or received a patent on their findings. Additionally, 68% stated that they had sent research tools to others in academia [1]. This is especially relevant in iGEM, a competition whose explicit aim is to remain open source and collaborative. We examine whether this is a realistic or achievable goal within the framework of patents in the scientific world.


Within iGEM, the stipulation that all BioBricks must remain open source and redistributable means that patented material is inherently excluded from submission. This sort of restriction differs somewhat from the usual research experience, where 91% of scientists have not checked for patents on the material they used in the last 5 years [1]. However, iGEM falls in a unique `grey area’, which effectively prevents the use of any patented materials by participating teams with the requirement to submit their parts to the Registry to be redistributed. Although teams are using parts solely for research purposes, the nature of the registry and iGEM’s distribution kits means that by redistributing parts iGEM would be infringing on the patent holder. The UQ-Australia iGEM team has had to remodel their circuit design after encountering patents on key components.


In the past, the issue of patenting has been less significant on iGEM with a recent survey indicating that less than twenty teams faced any legal issues regarding patenting and their parts [2]. This would likely be since the majority of teams worked in bacteria, where the parts have either never been patented, or any patents have since expired. However, as more explore synthetic biology in mammalian projects, patenting is going to become an unavoidable issue. Consequently, we propose two possible mechanisms for iGEM to handle patents on biological parts.


[1] Lei, Z, Juneja, R & Wright, BD, 2009, ‘Patents versus patenting: implications of intellectual property protection for biological research’, Nature Biotechnology, vol. 27, pp. 36-40.

[2] Mexico-UNAM-CINVESTAV, 2010, `Human Practices: Survey Results', accessed 4 August 2011 from https://2010.igem.org/Team:Mexico-UNAM-CINVESTAV/Home