A postgraduate research opportunity at the University of Otago.
Details
- Close date
- Friday, 31 March 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. MP structure and function depend on the complex composition and architecture of biological membranes. 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 (SMA) polymers to extract and purify homogenous, functional, C. albicans Cdr1 lipid nanoparticles (Cdr1-SMALPs) together with their essential native plasma membrane lipid constituents. Cryo-electron microscopy and 3D-reconstruction of these native Cdr1-SMALPs will generate the first structure for the native Cdr1 MP-lipid complex. This structure will be compared with the structure of detergent-purified Cdr1 MP preparations. Detailed biochemical and structural investigations of these Cdr1 MP preparations will reveal how the plasma membrane lipid 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 successful candidate will have obtained bachelor’s degree, BSc(Hons) or BBioMedSci(Hons) or MSc with high academic excellence. Knowledge of bioinformatics and protein chemistry would be desirable. The student selected for this project will join a multidisciplinary internationally recognized 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 Assistant Professor Isabelle Rouiller, University of Melbourne, and X-ray crystallography at the University of Otago.
Value, tenure and supervision
- The PhD scholarship, funded by the Royal Society of New Zealand Marsden Fund, includes a NZ$35,000 tax-free stipend plus PhD fees for three years
- This project will span three years
- Start date is flexible between April and September 2023
- The recipient will be supervised by Dr Erwin Lamping and Professor Richard Cannon at the Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand
- Single particle analysis and cryoEM will be initiated in-house under the guidance of Associate Professor Mihnea Bostina at the Otago Micro and Nanoscale Imaging facility
- High resolution structures of promising Cdr1 MP-nanoparticle preparations will be determined at the Melbourne Advanced Microscopy Facility in collaboration with Associate Professor Isabelle Rouiller, School of Biomedical Sciences, The University of Melbourne, Australia
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 detailed curriculum vitae
- Certified academic transcripts
- Contact details of two academic referees
- One A4 page cover letter outlining your interest in the topic
The application closes on 31 March 2023, or as soon as a suitable candidate is found.
Please email your application to Dr Erwin Lamping before the closing date.
Email erwin.lamping@otago.ac.nz
