Project description
A tale of a tail: understanding self-assembly of multiple proteins into functional nanomachines
Bacteria move around using flagella, propeller-like appendages that allow directed movement towards nutrients, other attractants and preferred sites of infection. About 20 nm in diameter, the flagellar filament is rotated by a motor located in the cell envelope. The entire flagellum is a complicated nanomachine in which multiple proteins form the rings that anchor the flagellum in the membrane, act as the motor and form the filament itself. While other studies have focussed on genetics and the characterisation of subcomponents, the EU-funded BacNanoMachine project plans to enhance our understanding of the coordinated self-assembly of all the building blocks in bacteria in time and space. It will advance our basic understanding of these processes and potentially also have implications for the rational design of novel antibiotics and for synthetic molecular machines for a variety of applications.
Objective
Life has evolved diverse protein machines and bacteria provide many fascinating examples. Despite being unicellular organisms of relatively small size, bacteria produce sophisticated nanomachines with a high degree of self-organization. The motility organelle of bacteria, the flagellum, is a prime example of complex bacterial nanomachines. Flagella are by far the most prominent extracellular structures known in bacteria and made through self-assembly of several dozen different kinds of proteins and thus represents an ideal model system to study sub-cellular compartmentalization and self-organization. The flagellum can function as a macromolecular motility machine only if its many building blocks assemble in a coordinated manner. However, previous studies have focused on phenotypic and genetic analyses, or the characterization of isolated sub-components. Crucially, how bacteria orchestrate the many different cellular processes in time and space in order to construct a functional motility organelle remains enigmatic. The present proposal constitutes a comprehensive research program with the aim to obtain a holistic understanding of the underlying principles that allow bacteria to control and coordinate the simultaneous self-assembly processes of several multi-component nanomachines within a single cell. Towards this goal, we will combine for the first time the visualization of the dynamic self-assembly of individual flagella with quantitative single-cell gene expression analyses, re-engineering of the genetic network and biophysical modeling in order to develop a biophysical model of flagella self-assembly. This novel, integrative approach will allow us to move beyond the classical, descriptive characterization of protein complexes towards an engineering-type understanding of the extraordinarily robust and coordinated assembly of a multi-component molecular machine.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
10117 Berlin
Germany