Enhancing precision-cut lung-slice models with computational modelling and machine learning to understand mechanobiology in airway remodelling


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  Prof Bindi Brook  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

One of the key characteristics of asthma is the irreversible structural changes that occur in the airway wall, termed airway remodelling. This typically consists of increased amounts of airway smooth muscle and increased extracellular matrix among other changes. Recent evidence suggests that forces transmitted by contracting smooth muscle cells to airway tissue can activate growth factors that cause airway remodelling in asthmatics, worsening the condition. The link between tissue mechanics and biology in vivo is not well understood but is key to developing a complete understanding of airway remodelling. In this project we will bring together an experimental ex vivo model called precision-cut lung-slice (PCLS; in which cells maintain their contractile ability in their native environment) with histological staining (to identify different cell types and proteins), machine learning to enable automatic detection of airway constituents from stained PCLS, spatial transcriptomics and predictive mathematical models to predict sites of growth factor activation within the airway wall. You will join a multidisciplinary team that values collaboration and team working. You will have the opportunity to develop both cutting-edge wet-lab skills working with animal and human PCLS as well as computational quantitative skills in developing predictive mathematical models and machine learning approaches.

Computer Science (8) Mathematics (25)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council. If successful, you will receive a stipend (currently £18,622 per year for 2023/24) and tuition fee waiver for 4 years. Successful candidates will also receive an allowance for a laptop, a travel and conference allowance plus allowance for laboratory/PhD running costs.
Click on the institution website link which will redirect you to the MRC AIM website which contains full application information including application forms to complete. Please ensure you submit your application before the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

References

1. Joseph, C. and A.L. Tatler, Pathobiology of Airway Remodeling in Asthma: The Emerging Role
of Integrins. J Asthma Allergy, 2022. 15: p. 595-610.
2. Tatler, A.L., et al., Differential remodeling in small and large murine airways revealed by novel
whole lung airway analysis. Am J Physiol Lung Cell Mol Physiol, 2023. 324(3): p. L271-L284.
3. Tatler, A.L., et al., Integrin alphavbeta5-mediated TGF-beta activation by airway smooth
muscle cells in asthma. J Immunol, 2011. 187(11): p. 6094-107.
4. Oenema, T.A., et al., Bronchoconstriction Induces TGF-beta Release and Airway Remodelling
in Guinea Pig Lung Slices. PLoS One, 2013. 8(6): p. e65580.
5. Madissoon, E., et al., A spatially resolved atlas of the human lung characterizes a glandassociated immune niche. Nat Genet, 2023. 55(1): p. 66-77.
6. Hiorns, J.E., et al., Airway and Parenchymal Strains during Bronchoconstriction in the Precision
Cut Lung Slice. Front Physiol, 2016. 7: p. 309.
7. Pybus, H.J., et al., Reduced biomechanical models for precision-cut lung-slice stretching
experiments. J Math Biol, 2021. 82(5): p. 35.
8. Tatler, A.L., Asthmatic airway remodeling: long overlooked but too important to ignore. Ann
Transl Med, 2023. 11(2): p. 29.

Where will I study?

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