Development of an in vitro nebulisation assay for use with defence pathogens (R230117)
Aston University
Basis: Full Time Closing Date: 23.59 hours BST on Monday 31 July 2023 Reference: R230117 Release Date: Monday 22 May 2023
Department: College of Health and Life Sciences
Contract Type: Fixed Term
Basis: Full Time
Closing Date: 31st July 2023
Supervisor: Dr Jonathan Cox
Project Reference: HLSCoxDSTL
Key words: Defence pathogens; Lung infection; Nebulisation; Antibiotic discovery
Applications are invited for a three-year Postgraduate studentship, supported by the Defence Science Technology Laboratory (DSTL) and the College of Health and Life Sciences, to be undertaken within the Biosciences Research Group at Aston University. The successful applicant will join an established experimental group working on antibiotic drug discovery and development.
The position is available to start in October 2023.
Financial Support
This studentship includes a fee bursary to cover the home/EU fees rate, plus a maintenance allowance of £18,622 for 2023/4. This application is only available to Home students.
Overseas Applicants
This application is not available to Overseas students.
Background to the Project
This project involves the development of an in vitro , animal-free nebulisation assay to assess the efficacy of new drugs and formulations against defence bacterial pathogens that pose a threat by respiratory infection. This 3-year PhD studentship will build on previous work from the Cox lab at Aston University, to develop and test this platform for inclusion in DSTL antimicrobial development pipeline as a prerequisite to in vivo efficacy assessment.
Bacterial pathogens of interest to the defence community share a number of common characteristics including a low infectious dose by the respiratory route and an ability to result in acute lethal, or debilitating, infections. Notable examples include Burkholderia pseudomallei , Francisella tularensis and Coxiella burnetii , the causative agents of melioidosis, tularemia and Q-fever respectively. They are generally difficult to treat and have limited treatment options. They are all zoonotic pathogens that are endemics in some parts of the world and therefore also have clinical relevance to human health. Development of novel antibiotics, or adjunct combinational therapies, that enhance current options for treating pneumonic infections caused by these pathogens would provide value to both defence and clinical research communities.
One of the challenges in developing therapeutics is the rational in vitro down selection of promising candidates, particularly with respects of which ones to transition into in vivo models. Furthermore, how best to ensure that the animal models employed for pre-clinical screening are predictive of therapeutic outcomes in people. The aim of this project to address these challenges.
We will first aim to develop a quantitative readout for the previously developed qualitative assay and use this for assessment of surrogate BSL-2 strains of defence pathogens. These will be assessed against nebulised known antibiotic formulations at the equivalent human dose.
This assay will then undergo further development to include infected macrophages, to establish persistence of the organisms in infected alveolar macrophages during nebulisation treatment. Cells will be used from different species (e.g. mouse, NHPs, humans), producing a methodology that would allow in vitro extrapolation of therapeutic benefit that translates from animal model to humans. This will be validated using a reference antibiotic for which data sets are already available. DSTL will provide data for the performance of these antibiotics in animal models.
The continuation of this project will involve adapting the assay and validation under BSL-3 conditions including defence pathogens of interest ( F. tularensis , B. pseudomallei and C. burnetii ) with and without macrophages.
Person Specification
The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in a disciplined aligned to the following subject areas: Microbiology, Human Biology, Biochemistry, or Biomedical science. Preferred skill requirements include practical experience of microbiology research and candidates with prior experience of working with BSL-3 pathogens are particularly encouraged to apply. Applicants for this PhD position must be British Nationals to be progressed in the recruitment process.
Contact information
For formal enquiries about this project contact Dr Jonathan Cox by email at [email protected]
Submitting an application
As part of the application, you will need to supply:
Details of how to submit your application, and the necessary supporting documents can be found here.
Please select “Research Biomedical Sciences” from the application form options.
The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.
Please include the supervisor's name, project title and project reference in your Personal Statement.
If you require further information about the application process please contact the Postgraduate Admissions team at [email protected]