Understanding how bacteria sense and adapt to their environment

In order to survive, bacteria must be able to sense and adapt to their (changing) environment. This includes pathogens trying to establish infection in a human host. The Rrf2 family of regulators is widespread amongst bacteria and controls some of the most important cellular pathways, including iron metabolism, iron-sulfur biogenesis and responses to oxidative and nitrosative stresses. Many Rrf2 family regulators bind an iron-sulfur cluster, and this is the key sensory module of the regulator. It turns out that, although Rrf2 proteins are very similar to one another, the type of cluster they bind, and the way that they do it, varies from one family protein to another. This project is focused on determining cluster type and coordination and understanding the important factors that control these characteristics. The consequences of altering cluster coordinating residues on cluster type and functionality will also be investigated. Training will be provided in a wide range of techniques during the project, including protein purification, anaerobic protein handling, iron-sulfur cluster chemistry, protein-DNA interactions, spectroscopy, mass spectrometry and X-ray crystallography.