Design and synthesis of selective anion receptors to facilitate transmembrane anion transport in epithelial cells

Summary

CF is a recessive genetic condition that results from the dysregulation of anion transport through the cystic fibrosis transmembrane regulator anion channel in epithelial cell membranes. Chloride flux through the CFTR channel is impaired in CF, resulting in chronic lung disease in most CF patients. The development of synthetic anion transporters has recently attracted much interest as these compounds could be used to replace the function of the faulty chloride channel. However, most synthetic chloride transporters have been shown to also transport protons. As a result, these compounds depolarise acidic compartments within cells triggering cell death.

We are currently developing compounds which selectively transport chloride but do not dissipate pH gradients which may be used as future therapeutic agents for CF. In addition, we are developing new synthetic ionophores with controllable ON/OFF smart functionalities to mediate programmable localised cell death. Our strategy is to exploit the specificity of pH, redox potential and membrane composition in cells as internal stimuli, and/or the involvement of light or chemicals as external stimuli.

Supervisor

Professor Philip Gale.

Research location

School of Chemistry

Program type

Masters/PHD

Synopsis

All projects in the Gale group will involve synthesis and a range of experimental studies to investigate how your supramolecular molecules interact, and evaluate their functional properties using techniques such as NMR, UV‐Vis and fluorescence spectroscopies, isothermal titration calorimetry, electrochemistry and computational chemistry. We specialise in using phospholipid liposomes as cell membrane models to elucidate transmembrane transport kinetics and mechanisms.

There will also be opportunities to see your project extending through collaborations with the world‐leading crystallographers to study the structure of receptors and complexes in the solid state, also biologists and biophysicists to investigate the properties of these functional molecules in cells.

Additional information

Postgraduate research scholarships are available for both domestic and international students. Most domestic students are supported by the Australian Government Research Training Program (RTP) scholarships and University of Sydney Postgraduate Awards (UPA). International students will need to obtain the Australian Government Research Training Program (RTP) Scholarship (International) or have appropriate funding from another source. Please contact me for further details.

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

• Confidential disclosure and registration of a disability that may hinder your performance in your degree;
• Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
• Ability to perform independently and/or with minimal supervision;
• Ability to undertake certain physical tasks (e.g. heavy lifting);
• Ability to undertake observatory, sensory and communication tasks;
• Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
• Ability to work in confined spaces or at heights;
• Ability to operate heavy machinery (e.g. farming equipment);
• Hold or acquire an Australian driver’s licence;
• Hold a current scuba diving license;
• Hold a current Working with Children Check;
• Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Opportunity ID

The opportunity ID for this research opportunity is 2475