Dr. Coli: A bacterial drug delivery system

Our team works on a bacterial drug delivery system, for instance for the production of a peptide such as vasoactive intestinal peptide as a potential treatment for Crohn's disease. The bacterial drug delivery systems will have several advantages over classical drugs. These are (a) the bacterium will produce the exact amount of drug necessary for each individual by means of an indirect feedback control mechanism, (b) the bacterium will die upon a long symptomless period and (c) a possible development towards drugs being taken up in the bloodstream. The elaboration of such a system in a couple of months is, however, not viable. Therefore, we have decided in favour of constructing something more like a scaffolding, a proof of concept, that uses dummy in- and output and leaves room for case-dependent interpretation. Crohn's disease is, for us, only an example, rather than a limitation.

A dummy input has been found in a light-sensing device. This is an easy-to-use system, that allows fast switching between input signals 0, noise or 1. The dummy output signal is, for more or less the same reasons, expression of a fluorescent protein. Its signal is easy to follow in time and intensity, in a non-invasive way. This input-output line is the main backbone of the project. However, without decent control, this system is worthless. First, the project includes a way of filtering noise out of the input signal. Secondly, we want the system to shut down once the infection has been overcome. Therefore, an inverter, a clock and a cell death mechanism have been placed in cascade. That way, when no input signal is present, the inverter makes sure a clock starts and keeps ticking, eventually leading to cell death after some time. And thirdly, it is interesting to be able to shut down and reset the clock upon renewed presence of input signal to overcome a phase of latently present input signal. The quick-witted scientist will of course notice that this system is doomed to fail, as all cells will die on their own. That is why the fourth and last control mechanism is a memory device. This stable switch is activated by the first input signal, and remains in a set ON state for the rest of its life. Only in this ON state, the clock can start ticking. These control mechanisms are very much dependent on kinetic and other constants. Therefore, proper modeling of this system is indispensable. In a later stadium, data analysis will prove its function in fine-tuning the model. We hope that these interactions between experiments in vitro and in silico will lead us to decent results.