PROJECT
Design and development of novel therapeutics for multidrug resistant bacteria
New therapeutics to treat multidrug resistant bacteria
Multi-drug resistance (MDR) in Gram-negative bacteria has been identified as a major worldwide public health concern.
Multi-drug resistant bacteria are responsible for approximately 700,000 deaths per year, a figure which could reach 10 million by the year 2050.
This project focuses on developing inhibitors of an endotoxin modifying enzyme that mediates antibiotic resistance by masking bacteria against both the human immune system and important classes of antibiotics. A structure guided approach will be used to develop novel therapeutic agents to treat MDR bacterial infections.
Through this project you will acquire skills in recombinant protein expression and purification. You will learn all aspects of protein crystallography including crystallisation, X-ray diffraction data collection and structure determination.
You will also obtain expertise in other biochemical and biophysical methods used to characterise the protein and its interactions with small molecule inhibitors.
As a multidisciplinary project, it provides opportunities for skills in structural biology, protein chemistry, biophysics and computational chemistry. You will work as a park of a team with medicinal chemists and microbiologists.
Find out more about research team leader, Professor Alice Vrielink or for more background information, see the suggested readings below.
- Suggested readings
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- Anandan, A., Evans, G.L., Condic-Jurkic, K., O’Mara, M.L., John, C.M., Phillips, N.J., Jarvis, G.A., Wills, S.S., Stubbs, K.A., Moraes, I., Kahler, C.M. & Vrielink, A. (2017). Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding. Proceedings of the National Academy of Sciences USA, 114, 2218-2223.
Project goals
Elucidate structures of the enzyme in complex with small molecule inhibitors
Determine the binding affinities of the inhibitors for the enzyme
Use the structural information to optimise the inhibitors for enhanced potency
Research team leader: Professor Alice Vrielink
Our lab looks at the three-dimensional structures of proteins implicated in disease. We are focused on proteins that act as virulence factors causing antibiotic resistance as well as proteins that are important in causing cancer and tumorigenesis. We characterise the structures of these proteins and study their interactions with small molecule inhibitors as part of the process of structure-guided drug design.
News
Scientists 'unmask' superbug-shielding protein
Australian scientists have mapped the molecular structure of a protein that shields superbugs from antibiotics.
Read moreResearch to help fight multi-resistant bacteria
An international collaboration led by scientists from The University of Western Australia has uncovered the three-dimensional molecular structure of a protein, called EptA, which is responsible for multi-drug resistance in many disease-causing bacteria.
Read moreWA scientists fight deadly superbugs
UWA scientist Professor Alice Vrielink is leading the push to overcome the superbug threat. Alice and her team have provided world-first insights into one of the ways in which antibiotic resistance occurs.
Read moreHow to apply
Interested in becoming part of this project? Complete the following steps to submit your expression of interest:
Step 1 - Check criteria
General UWA PhD entrance requirements can be found on the Future Students website.
Requirements specific to this project:
- a knowledge of proteins including their basic structures and function
- biochemistry laboratory skills
Step 2 - Submit enquiry to research team leader
Step 3 - Lodge application
After you have discussed your project with the research team leader, you should be in a position to proceed to the next step of the UWA application process: Lodge an application. Different application procedures apply to domestic and international students.
Scholarships
- Domestic students
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All domestic students may apply for Research Training Program and University Postgraduate Awards (UPA) scholarships
- International students
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A range of scholarships are available from international organisations and governments. The full list, organised by country, is available on the Future Students website.
In addition, all international students may apply for International Research Training Program scholarships.
- Indigenous students
- Indigenous students are encouraged to apply for Indigenous Postgraduate Research Supplementary Scholarships.
- Forrest Foundation scholarships
- All international and Australian students who wish to study towards the degree of Doctor of Philosophy (PhD) at The University of Western Australia may apply for Forrest Scholarships.
Collaboration and volunteers
Collaboration partners
- Associate Professor Keith Stubbs, School of Molecular Sciences, UWA
- Associate Professor Charlene Kahler, School of Biomedical Sciences, UWA
- Dr Mitali Sarkar-Tyson, School of Biomedical Sciences, UWA
- Dr Charlotte Conn, RMIT University, Melbourne
- Dr Gerald Larrouy-Maumus, Imperial College, London, UK
Interested in volunteering?
Volunteers are welcome to help with protein production and crystallisation. Contact Professor Vrielink to register your interest.
