Lung diseases are responsible for a death every 5 minutes in the UK and cost the economy £5 billion per annum. Precision Medicine is a promising strategy, but requires a systems-level understanding of respiratory pathology. This is largely unexplored as there is no computational framework to link multiple biological scales. The overarching goal of this proposal is to build the Lung Pharmacome – an in silico lung capable of recapitulating personalised lung physiology and pharmacology based on patients’ omics profile to
i) understand mechanisms underpinning respiratory diseases,
ii) validate & prioritise respiratory therapies, and
iii) enable patient-specific modelling.
Projects are currently available under the following research motifs:
The Laboratory for Multiscale Emergent Bioengineering uses multi-paradigm computational tools to simulate patient-specific biology to understand how pathological gene activity scales across cell and organ levels during asthma and COPD. This entails developing models of gene regulatory networks, cellular interaction, and microenvironment gradients (including tissue/organ mechanics) and integrating them to create a ‘virtual patient’. The rationale is that following development the ‘virtual patient’ can be personalised based on patients’ transcriptomic, imaging, biopsy (etc) data. Thus, this virtual patient will further our understanding of the mechanisms that mediate respiratory pathology and also enable us to predict the clinical impact of novel therapeutics. For more information, refer to an earlier version of the ‘virtual asthma patient’ and the multiscale GARMEN. Projects (computation-oriented) available for undergraduate and postgraduate students. Contact if interested.
To validate the computational model’s ability to capture multiscale interactions and make clinically-relevant predictions, the lab will develop airway organoids featuring epithelial and mesenchymal cell types. Organoids are in vitro culture systems that reflect human physiology more closely than animal models and are ideal in capturing pathological architectural and transcriptomic characteristics. Engineering similar perturbations in the organoids, as introduced in the computational model, will enable robust testing and validation of computational predictions. This research motif will not only lead to novel culture protocols but also help us understand how fundamental mechanisms lead to variable systemic outcomes between different individuals. This will shed fundamental insights into responder vs non-responder effects and help engineer better therapies. Refer to this article for information on how multiscale computational models can be tested via in vitro organoids to discover biological mechanisms. Projects (experiment-oriented) under this research motif are only available at the postgraduate level (PhD or Maters by Research students).
Royal Academy of Engineering Research Fellowship
University of Leicester, January 2021 – January 2026
Michael Smith Foundation for Health Research Trainee Award
University of British Columbia, July 2019
Centenary Year Scholar
University of Oxford, May 2011
Una Goodwin Scholar
University of Oxford, September 2010