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Our PhD Studentship awards are open for outline applications! Awards of three/four years are available including joint awards with the BHF.

NC3Rs | 20 Years: Pioneering Better Science
PhD Studentship

An organotypic model of bronchial dysplasia

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At a glance

Award date
October 2015 - September 2018
Grant amount
Principal investigator
Dr Frank McCaughan


University of Cambridge


  • Replacement
Read the abstract
View the grant profile on GtR

Impact story

This project has been featured in an impact story, showcasing how NC3Rs-funded research comes together to develop innovative new 3Rs tools and technologies that are pioneering better science.

Application abstract

We have developed a novel organotypic (OTC) model of bronchial dysplasia/early lung cancer. In this system, immortalised normal human bronchial epithelial cells are grown at the air-liquid interface on a collagen matrix with embedded fibroblasts. In OTC there is a clear phenotype in cells in which the activation of putative oncogenes at the air-liquid interface recapitulates a histological phenotype consistent with human bronchial dysplasia / early lung cancer.

In vivo, multiple potentially important genotypes may co-exist and influence the cellular phenotypes. We have introduced complexity into our model by combining two genetic lesions, which leads to a more marked phenotype. For this studentship we propose two main scientific objectives:

(I) To perform a medium throughput functional/phenotypic screen of an extended library of small molecule inhibitors in an in vitro model of bronchial dysplasia.

The student will first recapitulate the current OTC experiments and optimise them for a 96- transwell format (rather than current 12 well format) more suitable for screening therapeutic compounds. A 384-compound commercially available library that targets multiple key signal transduction pathways and comprises all classes of known anticancer compounds will be used. The impact of these compounds on the dysplastic phenotype will be interrogated.

(II) To extend the existing in vitro OTC model to cover more complex genotypes and assess the impact of these changes on hits from Aim I. Using existing lentiviral protocols and the recently introduced CRISPR technology further/other genetic lesions will be introduced into the same immortalised cells with the aim of producing the more complex genotypes. Further, the microenvironment will be manipulated. The impact of these refinements on the development of dysplasia and the effect of anticancer compounds will be interrogated.