Research Highlights

Prof. dr. Jan Kok

Spatial organization of mRNA, plasmids, and ribosomes

Production of heterologous membrane proteins in bacteria such as E. coli and L. lactis is far from trivial^a. Many studies have focused on pinpointing and alleviating obstructions in the process and mostly have been performed at the level of cultures not taking into account that individual cells in a bacterial populations can respond differently under homogeneous conditions. The Kok group (together with Poolman and van Oijen) focuses on single cells of L. lactis using various state-of-the-art fluorescence microscopy techniques. Not only the fate of proteins but, most importantly, that of the messenger RNAs encoding the overexpressed membrane proteins was determined^b. Poorly expressed membrane proteins experience obstacles during translation, leading to polar transcript accumulation (see figure, green spots in the right cell) and cessation of cell growth. The immobile mRNA clusters are spatially distinct from protein aggregation seeds and mRNA production sites. Once their disassembly is initiated, a synchronized restoration of translation and growth takes place. The aberrant features of mRNAs could be reversed by engineering the N-terminus of the encoded protein. The findings add an empirical understanding of why certain membrane proteins are poorly expressed in bacterial production platforms.

^a PLoS One (2011); ^bPLoS Genetics (2016);