Industrial Partner: Tocris Bioscience
Background:
Infectious diseases remain among the biggest challenges to human health, accounting for >2.5 million deaths worldwidein 2019 and with predictions of >3 million by 2030. Despite our increased knowledge of respiratory-borne microbes and the responses they trigger in the host immune system, detailed understanding of how pathogens and host cells interact in the human lung is essential to design therapies that overcome our reliance on antimicrobials.
Agents able to modulate immune responses can improve bacterial clearance but we have limited information on the molecular mechanisms behind such protective responses. Furthermore, there is a paucity of imaging tools that can provide quantitative readouts on how immune cells respond to drugs in situ. Our strategy is to develop a novel multiplexed live-cell imaging platform to monitor how pathogens and immune cells interact in the lung, accelerating the validation of new therapeutic strategies for infectious diseases.
We will build a multiplexed sensing toolbox to monitor activity-based biomarkers of immune cell function. We will use this platform to profile the metabolic activity of model systems as well as bronchoalveolar lavage fluid samples from patients with pulmonary infection. We will prepare targeted biosensors to image macrophage, neutrophil and T cell activity in bacterial infection models of increasing complexity. First, we will optimise the sensors in live cultures of drug-resistant pathogens (e.g., S. pneumoniae among others) and human primary cells. Next, we will validate selected sensors in preclinical models, including lung-on-chips that recapitulate environmental factors of pulmonary physiology. Finally, we will perform imaging in ex vivo human lung tissues to accelerate the translation to future clinical studies. We will prepare for translation and clinical readiness of the selected biosensors together with Tocris enabling us to move this technology into early phase clinical trials.
Aims
Our main aim is to combine metabolomics, chemical biology and imaging to develop a collection of biomarkers to characterise metabolic signatures of immune cell function and translate them into a decision-making tool for enhanced treatment of infection diseases.
Training Outcomes
Generic and transferable skills provided by the supervisory team:
* Development of an in vitro metabolomic platform for the optimisation of targeted biosensors.
* Data analysis and management, mining skills and bioinformatics.
* Design and optical fingerprinting of activity-based biosensors.
* Cell culture, microscopy, flow cytometry, functional assays, lung-on-chip and immunohistochemistry.
* Assessment of optimal agents in ex vivo human tissues.
* Image analysis (qualitative and quantitative).
* Research ethics and health and safety skills.
* Target Product Profile based on current standard of care and technical feasibility (with Medical Innovations Team and Tocris).
* Participation in the development of marketing strategy through competitive landscape and future emerging technologies (with Medical Innovations Team and Tocris).
* Study IP landscape and freedom to operate. Secure emerging IP, including paper and patent writing.
* Communication skills.
About the Programme
This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.
All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.
http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919
Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.
For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine
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