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Structure of fungal ABC membrane protein Cdr1 embedded in native lipids

A postgraduate research opportunity at the University of Otago.

Details

Close date
Friday, 13 January 2023
Academic background
Health Sciences
Host campus
Dunedin
Qualification
PhD
School
Faculty of Dentistry
Supervisors
Dr Erwin Lamping, Professor Richard Cannon, Associate Professor Mihnea Bostina, Associate Professor Isabelle Rouiller

Overview

Drug resistance of the major human fungal pathogen Candida albicans is caused by the overexpression of plasma membrane protein (MP) Cdr1.

Structure-directed drug design can overcome MP-mediated resistance, but this relies on correct MP structures. It is evident that MP structure and function depend on the complex composition and architecture of biological membranes. Unfortunately, many MP structures solved to date are unnatural because they were generated with detergent-solubilized MP preparations stripped of their structure and function-defining lipid components.

This project will use styrene maleic acid polymers to extract and purify homogenous, functional, C. albicans Cdr1 nanoparticles together with their essential native plasma membrane lipid constituents. Cryo-electron microscopy and 3D-reconstruction of these native Cdr1 nanoparticles will generate the first structure for the native Cdr1 MP-lipid complex. We will compare this structure with the structure of detergent-purified Cdr1 MP preparations, and we will investigate how membrane composition affects Cdr1 structure and function. Understanding how membrane-lipids interact with Cdr1 will have fundamental implications for future MP research and for structure-directed drug design.

We are looking for a well-qualified and highly motivated student to embark on a PhD project as part of this study. The student selected for this project will join a multidisciplinary internationally recognised research team. The project will involve state-of-the-art detergent-free membrane protein purification and structural analysis using single particle analysis and cryo-electron microscopy of Cdr1 under the guidance of Associate Professor Mihnea Bostina, University of Otago, and Associate Professor Isabelle Rouiller, University of Melbourne, and X-ray crystallography at the University of Otago.

Value, tenure and supervision

Applicant eligibility

This PhD scholarship is open to domestic and international candidates with an excellent GPA and good English writing and communication skills.

How to apply

  • A full curriculum vitae
  • Academic transcript
  • Contact details of two academic referees
  • One A4 page cover letter outlining your interest in the topic

Please email your application to Dr Erwin Lamping before the closing date: 13 January 2023.
Email erwin.lamping@otago.ac.nz

Contact

Erwin Lamping
Tel   +64 22 644 6471
Email   erwin.lamping@otago.ac.nz