Investigating the mechanism of phosphate aquisition by Pseudomonas aeruginosa

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Phosphate is an essential nutrient that is found in lipids, nucleic acids, proteins and sugars and is also key to many biological reactions that require ATP and/or signaling pathways that exploit protein phosphorylation. Thus, bacteria utilize a global regulatory circuit, the Pho regulon, to manage intracellular bacterial phosphate homeostasis. The Pho regulon regulates the expression of key proteins involved in the acquisition of phosphate, including integral membrane proteins that play an important role in the transport of phosphate across lipid bilayers and into the cell. These membrane proteins also act as sensory proteins that interact with phosphate binding proteins to detect the levels of extracellular phosphate and in turn regulate their own expression through the Pho regulon. The Pho regulon pathway also controls many other gene networks including the expression and secretion of virulence factors in response to phosphate levels, thus this phosphate acquisition pathway in bacteria is extremely important. The integral membrane proteins (OprP and PstABC) that translocate phosphate interact with their aqueous soluble transport partners (PstS and PhoU) facilitating the transport of these anions and also initiate signaling events that are propagated to control gene expression. Research in the Moraes lab will examine the protein interactions between integral membrane protein transporters and their soluble transporter counterparts that lead to transport and signal transduction. We plan to dissect the components of this pathway and their interactions in molecular detail using tools such as X-ray crystallography to provide atomic resolution 3D- images of the proteins involved in phosphate translocation. Indeed, the high-resolution structure of the outer membrane protein OprP determined by Dr. Moraes provides insight into the first step of phosphate acquisition. Highly qualified personnel will be well trained in the areas of membrane protein structural biology, microbiology, biochemistry and molecular biology, preparing them for careers in basic scientific research and biotechnology.