Research Supervisor Connect
Ion pumps determine such fundamental processes as nerve function, muscle contraction and digestion, and constitute a sizeable proportion of all drug targets. While major progress has been made in revealing the structures of specific ion pumps, the puzzle is still incomplete, and we do not know how the pumps actually work in a living organism. This is a key knowledge gap, which if tackled, will feed into structure-activity studies for new drugs. With drug resistance an ever-increasing problem, the identification of new drug targets is of vital importance.
In this project, the focus of attention will be the termini of the catalytic subunit of P-type ATPases, e.g., the Na+,K+,-ATPase and the H+, K+-ATPase. Prior research from our group suggests that the pumps’ N-termini undergo an electrostatic interaction with the surface of the surrounding lipid membrane and that this interaction controls the pumps’ conformational state and hence their activity. The hypothesis to be investigated in this project is that ion pump regulation occurs via an electrostatic-switch mechanism, in which the interaction of the N-terminus with the surrounding membrane is electrostatically controlled by phosphorylation of the N-termini by protein kinases. To investigate this interaction, we will utilise both purified ion pump preparations and synthetic peptides with amino acid sequences corresponding to those of the N-termini. To detect the strength, specificity and site of the interaction we will use a range of different spectroscopic techniques, i.e., fluorescence spectroscopy, circular dichroism, solid-state nuclear magnetic resonance spectroscopy, as well as quartz-crystal microbalance with dissipation monitoring.
Associate Professor Ron Clarke.
This opportunity/project is a part of the Faculty of Science Australian Research Council (ARC) Scholarship scheme and will be advertised on the Scholarship Office website starting mid-May 2025. The selected applicant is expected to commence their candidature in July (RP3) 2025 onward. Successful applicants will be supervised by A. Prof Ronald Clarke and focus primarily on their PhD projects. They will also have the opportunity to participate in any activities held at the University of Sydney under the ARC Discovery Project (DP). The candidate will be enrolled in the School of Chemistry, Faculty of Science at the University of Sydney.
Notes:
• The application process is separate from applying for admission to the University of Sydney.
• The scholarship will only be awarded once the successful scholarship applicant has received an unconditional offer of admission.
• International applicants are responsible for securing any necessary visas and costs to enable study based in Sydney.
The opportunity ID for this research opportunity is 3595