Can we predict the behavior of a live organism throughout its proteins and genes in the same way as we do it with a machine through its components? This is a key queston for many experts in synthetic biology: a discipline that looks for the application of engineering in th design of new genetically modified organisms. Scientist from the Complex Systems Lab have developed a mathematical model that predicts the gene expression of an organism and have concluded that, far from following a logic based on the peculiarities of biology, presents a striking parallel with the laws governing electrical circuits.

Genetic engineering is a reality

Synthetic biology aims to improve the functions of organisms by giving them capacities they originally did not possess. Behind this trend are projects such as the fight against malaria or the generation of new energy sources of biological origin. The changes in the body are made possible by genetic engineering, which can add genes from other species to an organism. Synthetic biology not only seeks to introduce a new gene, but the necessary instructions that determine when and when not the body must perform that function.

Nevertheless, when a new gene is introduced in the DNA of a cell, cellular stress is generated, causing an extra load in the cellular genetic expression and affecting to its metabolism. This load makes it impossible to predict the behavior of a full genetic circuit by characterizing the individual genes that compose it, being this one of the greatest limitations for the progress of synthetic biology.

The genetic expression of a cell depends on the resources that it can reach, so if the genetic expression demand increases (as a consequence of the addition of a new gene, for example), but the cellular resources are maintained, the final result of the genetic expression will be altered. In the same way that sometimes we switch on a stove in our house and we notice that the light bulb in the room suffers, adding a gene to a living organism can affect the expression of another gene, however the little relationship they seem to have.

More than an electric principle

The team led by Carlos Rodríguez and Javier Macía has developed a mathematical model to predict the genetic load that a cell will suffer when a particular gene is introduced. The mathematical model has resulted in a formula surprisingly similar to the Ohm's law that governs electric circuits in series.

This mathematical model has been validated experimentally with bacteria. The authors of this scientific article thus confirm that a genetic circuit in response to an increasing number of genetic loads behaves analogously to an electric circuit with resistances in a series connected to a real power supply. The formula obtained and its validation demonstrate that genetic load is an additive property that allows the predictability of the whole system's behavior, a key step in genetic engineering that until now could not be achieved.

Genetics is not the only field where an adapted Ohm's law seems to fit. Previous studies show that other circuits, like bloody circulatory system or body heat dissipation, can also be described following the Ohm's law. "Ohm's law could be a more general principle that goes beyond the electric metaphor", comment the authors. This study suggests the existence of a more fundamental principle that may emerge in systems where there is competition for shared limited resources needed to perform different activities of regulation.

Reference Article: Carbonell-Ballestero M, Garcia-Ramallo E, Montañez R, Rodriguez-Caso1 C, and Macía J (2015). Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law. Nucleic Acids Research