Effects of the spatial distribution of resources on the performance of genetic circuits

The availability of transcriptional and translational resources plays an important role in gene expression and is a key factor affecting the performance of synthetic genetic circuits and metabolic pathways. While there are extensive investigations of trade-offs between growth, cellular capacity for gene expression and allocation of cellular resources, little is known about how the spatial distribution of these resources impacts gene expression. Contrary to common assumptions, even simple cells lacking organelles like bacteria are heterogenous and far from well-mixed vessels where biochemical reactions take place. In particular, it has been demonstrated that well-characterised microorganisms such as Escherichia coli have a non-homogenous distribution of the transcriptional and translational machinery.

In this project we will investigate how the cytoplasmic location of the genes and the resources required for expression affect the performance of genetic circuits. Some pioneering works show that the distance between genes composing the same circuit influences their dynamic behaviour given that molecules such as transcriptional regulators need to diffuse to different regions of the cell2. Likewise, non-homogeneously distributed ribosomes and RNA polymerases need to diffuse to the locations of the cell at which the relevant mRNAs and proteins are produced. We hypothesise that the 'local' demand for resources plays a role in determining the final expression levels of genes of interest. Considering space as a design variable is, therefore, a novel aspect of synthetic biology that we will assess in this project.