Dynamics of the Type 3 secretion system translocase(DOT3S)

The type III secretion system performs specialized protein export. Its central component is the injectisome, a miniature syringe that sticks out of bacterial cells and jabs eucaryotic membranes. Pathogenic bacteria use it to deliver toxins directly into eukaryotic cells. To control pathogenicity, we need to understand what the injectisome looks like and how it works. For years scientists have tried to do this in living bacteria by removing injectisome components and by looking at them with powerful microscopes. We now propose a bold step to take these studies to the next level by focusing on how the components move. This dynamics approach entails observing how individual components move, away from the dizzying complexity of the cell. Motions will be studied using a globally unique collection of advanced complementary state-of-the art instruments and will be simulated in motion pictures generated by powerful computer clusters. They aim to learn which motions underlie the inner workings of the injectisome, in which order, how is metabolic fuel used to alter the strokes of the nanomachine and how poorly structured toxins that want to use to exit interact with it. This is a challenging goal as the dynamic nature of the injectisome has never been seen before and it is technically complex but Belgian lab and participating colleagues have the necessary expertise to tackle it. By better understanding this amazing nanomachine we hope to inspire future solutions for disease control.