Team:Wageningen UR/Project/Applications

Looking at a colony of bacteria under the microscope expressing fluorescent proteins in an oscillating manner sounds like fun, but the oscillating system might have real applications. We thought of an application that could be used in fundamental research that involves interactions between genes. To become familiar with this hypothetical application, an example is given:

Say, you have a particular gene A that you think interacts with other genes B, C & D, but you do not have evidence for this. To get an idea about this interactive behaviour you can knock out gene A. Now that gene A is knocked-out you want to find out what happened with genes B, C & D. One way is looking at the transcriptional level of those genes, to see whether there are differences compared to the normal situation. Another is measuring the concentrations of the proteins that are expressed by gene B, C & D. By looking at those data you can draw conclusions. For example, gene B seems to be up regulated, gene C seems to be down regulated and nothing happened to gene D. Now it seems that gene A interacts with both genes B & C, but there is still no hard evidence for that, as there is a dozen of other factors that could have influenced the expression of genes B & C. Think of growth conditions, growth phase, other gene interactions, etc.

Using the oscillating system, we can have gene A oscillating and at the same time look at what happens to the other genes B, C & D through time. If it appears that gene B shows changes in its expression level pattern or protein concentration pattern whilst gene A is oscillating and genes C & D do not show a difference compared to the normal situation, it means that there is hard evidence for the fact that gene A is interacting with gene B and not with gene C & D.

As there are some genes that cannot be knocked out, because without it the organism cannot survive, the use of knock-outs is limited. The oscillating system can get the expression level of crucial gene E very low at certain time points while it makes up for the loss at other time points where it is over-expressed. This means that, by looking at changing expression patterns of other genes over time, it is possible to get interactional information for gene E that until now was very hard to study.

Next to that, using the oscillating system, it would be possible to look at rates of interaction between genes. Imagine that gene B is regulated by gene A, which is oscillating. If the interaction speed between A & B would be extremely fast, it might be possible that gene B starts oscillating together with gene A. There should be a delay however. By looking at this delay and the resulting pattern of gene B, you could draw conclusions about the rate of interaction between both genes.

The oscillatory system could also be used in industrial applications. One application we came up with involves ranging enzyme concentrations. If for example a particular protein is manufactured by carrying out two different reactions in separate tanks by using an organism with an over-expressed enzyme A in tank 1 and another strain with over-expressed enzyme B in tank 2, we could do the same follow up of reactions in 1 tank using the oscillating system. For example, we could have a particular subset of enzymes produced in an oscillating manner so that the product is exposed to high concentration of enzyme A at a certain time point and a high concentration of enzyme B at another time point. This way the efficiency of such a process could be increased.