Regulation – a general introduction.
A cell is a complex whole system, it may also be a component of a larger more complex system – but the cell is a unitary level at which it is possible to manipulate, study, and model how living systems work. It will be clear to anyone following even a brief consideration, that the genes present in a cell do not determine the behaviour of that cell. They perhaps define the various potentials and capacities of that cell or organism – but they are similar to a library to which the cellular system refers in the way that students studying different subjects will select different materials for their studies.
We have to know which genes are present within cells to gain insights into what they are capable of. However, we have to understand how the expression of these genes is controlled in order to understand how and why they do the things that they do. So, for example, many species contain genes that could be associated with causing diseases, but most never do. Equally, many species that cause serious and not uncommon infections more normally live with and on their hosts (us) without causing any harm at all. While the same bacterium under different conditions will cause serious infection, and while it has all of the genes and capacity to do so, normally it doesn’t. As the song says: “It aint what you do, it’s the way that you do it” – and to understand the how and why bacteria cause disease, it is inadequate (although a pre-requisite) to simply know the genes that are present within it. The only way to understand the interaction of the bacterium and the host is therefore to understand how it controls, or at critical points loses control, of its gene expression.
There are a number of processes that contribute to the control of the bacterial system. Two of these are programmed regulation and phase variation (others include feedback inhibition and the roles of non-coding and other RNA-RNA / RNA-protein interactions). These are compared and contrasted in the following diagram, and it will be evident from this that they are very different from each other.
This comparison is a little simplistic, but it does illustrate the key points. A recent twist to this model is that the bacteria with different phenotypes in the same location may not actually compete with each other – but perhaps they co-operate in ways that enable the population to be successful in ways that more homogeneous populations are not - but that’s a subject for future work. Our approaches to each of these types of regulation are described on the web pages for phase variation and programmed regulation.