Research Supervisor Connect
Non-typhoidal Salmonella is a major cause of gastrointestinal disease worldwide and in Australia. Children under five and the elderly are the most vulnerable victims of Salmonella outbreaks. The natural habitat of non-typhoidal Salmonella is farm and pet animals. Although several animal-derived foods are known sources of reported outbreaks in Australia, egg and egg-based products remain the most common. Antibiotics are not commonly used in the treatment of non-typhoidal Salmonellosis, but multidrug resistant Salmonella are nevertheless on the rise and a serious public health concern nationally and globally. New therapies for the treatment of non-typhoidal Salmonella infections are urgently needed. This PhD research program will test whether bacteriophages are suitable to be used as substitutes or adjuncts to antibiotics to treat Salmonella infection or colonization, an important public health objective. The specific aims of the project are to identify phages against the dominant non-typhoidal Salmonella types in NSW; develop synergistic combinations of phages that have greater efficacy than the individual phages; test best phages and phage combinations to eradicate carriage of Salmonella in infected chickens and their eggs; and participate in the development of regulatory strategies in Australia for phage use. The successful candidate will build skills in the preparation of bacteriophage products to treat a classic “one health’ problem, responsible for major outbreaks of food-borne disease in NSW, by extending existing protocols for phage isolation, amplification and characterization to identify and test phages against the main Salmonella strains circulating in NSW and will link to other projects examining synergies of phages and antibiotics and resistance mechanisms. Preparations that appear to be effective in vitro will be purified to ‘food grade” level to be tested in in vivo models (chickens and eggs).
Sydney School of Veterinary Science
The primary question is whether bacteriophages are suitable to be used to substitute or synergise with antibiotics to treat Salmonellosis. The second question is whether phages can be used when antibiotics are not indicated, i.e. for ‘clearance/decontamination’ of Salmonella carriage as an equally important public health objective. The specific aims are to: 1. Identify phages against the dominant non-typhoidal Salmonella types in NSW; 2. Develop synergistic combinations of phages that have greater efficacy than the individual phages; 3. Test best phages and phage combinations to eradicate carriage of Salmonella in infected chickens and their eggs, and monitor phage pharmacokinetics; 4. Participate in the development of regulatory strategies in Australia for phage use, including the defining of phage passports.
The student will extend existing protocols for phage isolation, amplification and characterization to identify and test phages against the main Salmonella strains circulating in NSW and will link to other projects examining synergies of phages and antibiotics and resistance mechanisms. Preparations of material that appear to be effective in vitro will be purified to ‘food grade” level to be tested in in vivo models (chickens and eggs).
Technical skills will include molecular biology and advanced imaging techniques (transmission electron microscopy), clinical microbiology, and genomics skills. Broad microbiology skills include culturing and typing of Salmonella isolates, whole genome sequencing analysis, analysis of epidemiological and AMR data. Phage techniques include testing in vitro using Efficiency of Plating (plaque) assays as well as standardised growth curves in vitro, stability and host range.
Up to 500 Salmonella isolates from humans and animals will be genome sequenced and genomes analysed to determine dominant types and antimicrobial resistance patterns in the past 5 years. Three Salmonella isolates representative of the NSW population will then be used for phage cocktail design and optimization. Phages from our own extensive sets or isolated de novo from the environment (e.g. sewage) will be tested in vitro against the Salmonella collection to determine host range and efficacy. Phages with broader host range and best lysis will be selected, characterised, and synergies tested for cocktail design. For testing in animal models, phage extraction and purification methods will be compared for best result including octanol extraction of LPS, liquid chromatographic methods, in order to test stability at different purity levels. A “passport” will be defined for high-value phages, including electron microscopy and genome sequencing, basic stability and host range data, and synergy with antibiotics in vitro.
Testing of phages and cocktails in vivo will be in chickens and eggs following approved ethical study protocols for phage testing in animal models and experimentation in poultry. This is an excellent model for testing Salmonella infection treatment and food decontamination efficacy of bacteriophages that is uniquely available to the student through the collaborating One-Health team involved in this project. Infections will be monitored using imaging and growth-based assays. Standard growth curves will be used to define minimal inhibitory concentrations in vitro.
The student will undertake training in the R statistical package and bioinformatics focused on bacteriology and phage genomics, and to learn the ‘business’ side of phage therapy through specific commercial training (NSW Health) and to prepare ethics and regulatory documents under direct supervision. They will be supported by a team with the highest level expertise in phage biology and therapy, AMR genetics and genomics, animal and human pathogens.
This is a truly One-health approach dealing with the whole ecosystem of farming, food production, animal and human health, to establish effective phage therapy protocols in these areas.
This project is supported by a Postgraduate Research Scholarship of $40,000 per year (4 years duration) funded by NSW Health (OHMR) and the Westmead Institute for Medical Research and includes attendance to the Commercialisation Training Program and Program Evaluation.
Full Scholarship details: https://www.sydney.edu.au/scholarships/c/scholarship-in-phage-therapy-for-non-typhoidal-salmonella-infect.html
The additional supervisors for this project are Prof Jacqueline Norris and Prof Jonathan Iredell.
HDR Inherent Requirements
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:
You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.
The opportunity ID for this research opportunity is 3018