PROJECT
Combatting superbugs by cracking their resistance networks
Disarming microbes to break antibiotic resistance
Over the recent years, the frequency of multi-drug resistant bacterial infections has steeply increased, while the discovery and approval of new antibiotics is steadily declining.
Without concerted efforts by science and society to counteract these fatal trends, it has been estimated that microbial “superbugs” will become the number one threat to human health by 2050, leading to more than 50 million casualties per year.
On a molecular level, bacteria often gain high levels of resistance through the induction of arrays of defense mechanisms, protecting the target against the antibiotic attack. If we had a better understanding of the regulatory networks orchestrating these defenses, could we design novel strategies to break resistance? Could inhibitors of resistance gene expression serve as adjuvants to boost the potency of existing antibiotics?
To decipher the function of such complex antibiotic resistance networks in bacteria, our laboratory combines experimental methods from molecular genetics with mathematical modelling techniques from physics.
This interdisciplinary approach helps to identify some of the emergent properties of resistance networks, revealing striking features such as “active redundancy” in the regulation of individual resistance modules. Similar to highly redundant control systems implemented in airplanes, failure of individual resistance modules triggers compensatory up-regulation of other resistance mechanisms, leading to effective cell protection.
Based on these insights our research group seeks to develop novel strategies to interfere with the resistance gene expression network, using tools from systems and synthetic biology available in our lab. The current focus is to target cell wall antibiotic resistance in a range of Gram-positive bacteria, including the model organism Bacillus subtilis, but also the human pathogens Enterococcus faecalis and Staphylococcus aureus.
For more background information, see the suggested readings below.
- Suggested readings
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- From modules to networks: A systems-level analysis of the bacitracin stress response in Bacillus subtilis. Piepenbreier, H., Sim, A., Kobras, C. M., Radeck, J., Mascher, T., Gebhard, S. & Fritz, G., 1 Jan 2019, bioRxiv.
- Minimal exposure of lipid II cycle intermediates triggers cell wall antibiotic resistance. Piepenbreier, H., Diehl, A. & Fritz, G., 21 Jun 2019, In : Nature Communications. 10, 1, 2733.
- The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network. Radeck, J., Fritz, G. & Mascher, T., Feb 2017, In : Current Genetics. 63, 1, p. 79-90 12 p.
- Anatomy of the bacitracin resistance network in Bacillus subtilis. Radeck, J., Gebhard, S., Orchard, P. S., Kirchner, M., Bauer, S., Mascher, T. & Fritz, G., 1 May 2016, In : Molecular Microbiology. 100, 4, p. 607-620 14 p.
- A new way of sensing: Need-based activation of antibiotic resistance by a flux-sensing mechanism. Fritz, G., Dintner, S., Treichel, N. S., Radeck, J., Gerland, U., Mascher, T. & Gebhard, S., 21 Jul 2015, In : mBio. 6, 4, e00975-15.
As part of this PhD project the successful applicant will undertake:
- Molecular cloning
- High-throughput gene expression analyses
- Minimal inhibitory concentration assays
- Statistical data analysis
- Collaboration with national and international experts
- Presentation of scientific results
- Writing of scientific publications
Research team leader: Dr Georg Fritz
In 2019 I joined the School of Molecular Sciences at UWA as ‘Be Inspired’ Senior Lecturer and group leader for Synthetic Biology. In our research, we apply bottom-up and top-down approaches to combat antimicrobial resistance. This ranges from the design of synthetic genetic circuits to optimise the production of novel antibiotics, to the reverse-engineering of natural gene regulatory networks causing antibiotic resistance in bacteria.
Collaborations and volunteers
External collaborators:
- Dr. Susanne Gebhard, University of Bath, UK
- Dr. Josh Ramsay, Curtin University
Volunteers:
- Volunteers interested in laboratory internships are encouraged to contact Dr Georg Fritz
How 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 include:
- Demonstrated experience in bacterial genetics is essential
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.
