Studies of an iron transporter from human malaria parasite

Iron is an essential element for almost all life on Earth and it plays important roles in a variety of biological processes. However, iron can also be cytotoxic and levels of ferrous iron within cells must be tightly controlled. One method employed by cells to control iron levels is via activity of integral membrane iron transporter proteins. Despite the importance of these proteins in iron homeostasis they are still poorly understood. This project aims to better understand iron transport in the malaria parasite Plasmodium falciparum – one of the biggest killers of humans throughout history - via studies of PfVIT, a member of the vacuolar iron transporter (VIT) family. A pipeline is already in place for production of recombinant PfVIT to underpin the work. Functional characterisation of PfVIT will utilise purified wild type and mutant transporter reconstituted into liposomes to permit a detailed study of transport kinetics and mechanism. These studies will also determine unambiguously the component of the proton electrochemical gradient that drives the PfVIT-catalysed transport reaction. To facilitate these objectives we have designed a novel methodology for the unidirectional reconstitution of PfVIT into liposomes. Substrate-binding analyses of mutant protein will identify residues that form the substrate binding site(s).

Specific skills/experience required by applicants:

A keen interest in membrane protein biology.