Metal and the human microbiota – acquisition and regulation of a prokaryotic specific metal

Metal ions are vital for microbial metabolism. As enzyme cofactors, metals enable the use of energy sources often not accessible to the host, generate nutrients/energy sources for other microbes, and provide defense against molecular stresses. The total human microbiota inhabits diverse growth environments with different nutrient availabilities and stresses that will define specific metal needs. How do microbes discern metal availability at a molecular level in this different environment?

This question is multifaceted and of particular interest when considering metals needed only by microbial species but yet significantly impact the health of the host. This project will focus on prokaryotic metalloproteins involved in nickel acquisition and regulation to understand 1) how microbes identify metal species from diverse chemical environments and 2) how microbes detect intracellular metal levels.

Through biophysical characterization of these proteins, we will gain insights into nickel utilization in diverse locations linked to health (oral cavity and gut, for example) and disease (obesity and urinary tract infections, for example) as well as learning about the intracellular chemistry of uncultured or hard to culture microbes.

Training

Training will be provided in a breadth of techniques and concepts necessary to address the project goals. Practical training will cover bioinformatics analysis, recombinant protein overexpression and purification, biophysical methods for metal-binding assays, as well as well techniques necessary to interrogate gene regulation, metal content and physiology in selected species. More broadly, the project fits into the larger Metals in Biology grouping at Durham with regular opportunities to present and discuss results.