Team:UCL London/Project/Vision

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Vision

One vision for the future is that instead of detecting stressful conditions and subsequently alter or restore the global physical conditions in the bioreactor, the cells would instead be engineered to respond better to small alterations in their own micro environment. To do this the cells first have to be engineered to sense and respond to targeted stresses in a reliable way. Another possible further application for the future is that if these promoters are shown to work reliably they can be used in the same way as other inducible promoters. E.g. during bioprocessing it might be cheaper to spurge a large fermenter with nitrogen instead of enriched air for 10 seconds in order to start an induction, replacing inducing agents such as arabinose or IPTG. Or even better, as we know that the level of e.g. dissolved oxygen will be reduced as the cell concentration is increasing, we can let the cells produce the target protein for the process as soon the cells are concentrated enough to hit a lower oxygen level. Reaching a lower level of dissolved oxygen tension (DOT) means that the cells will not be able to grow so much further or at least not with the same speed as they have been growing until now. That normally means that it is a good time to induce the production of the target protein by adding an induction agent. Some stress responsive promoters could therefore be applied to make the induction step redundant in a particular bioprocess. These could be promoters responsive to e.g. oxygen, growth phase or acetate.

A more direct and probably the most straight forward application could be as an additional induction method. Hopefully it can be applied by synthetic biologists making biological systems that require many different inputs or combinations of inputs to yield a vast amount of responses.

Stationary growth

A self induced system used in monitoring growth phase. When it starts sensing a slow down in cell growth, this signal will induce the protein production instead of using an inducing agent. One additional advantage of this system, execpt making induction redundant, could be that it takes into account possible differences in growth phases on a cellular level.

Below is a process flow sheet describing the present way of detecting changes in oxygen for example.

Below is a process flow sheet entailing the future of internal sensing systems.

Advantages of the internal sensing system.

1. Removes the need to change the macro-environment of the cells in order to change the micro-environment of the cells.

2. Sensor will indicate deceleration phase of the growth of the cells.

3. Able to reduce transcription/translation depending on the amount the cell can cope with.

4. Human error reduced as the need of an operator is eradiated