Dr Diane Lee
Diane is an ex vivo and in vitro cell biologist with considerable experience in drug discovery and pre-clinical research in both industry and academia.
Having embarked upon a career in oncology and cancer therapeutics, Diane spent time at the Institute of Cancer Research, developing cell based and biochemical assays. From here she moved into the field of epigenetics at the Marie Curie Research Institute, studying the role of TAF5 in eukaryotic gene transcription, using site-directed mutagenesis and working with colleagues to develop an in vitro model of eukaryotic gene transcription. Her work was crucial in the confirmation of the dimeric structure of this transcription factor. Diane went on to gain extensive technical expertise in primary and 3D tissue culture at Novartis, working in the Gastro-Intestinal Disease Area in Horsham. Here she developed culture techniques of human and mouse small intestinal epithelial cells (SIECs) and colonic epithelial cells (CECs) as organoids, using them to study mechanisms of mucositis and therapeutics/prevention thereof. Upon the closure of GIDA, she moved back into academia, starting her PhD in 2011 at the School of Pharmacy and Biomolecular Sciences at the University of Brighton. Here she developed an in vitro model to enable pre-clinical identification of drug irritancy and permeability issues in the lung as part of ADME determination, completing her PhD in 2015.
Currently, Diane fulfils the role of Research Fellow in Pathology and Infectious Diseases and is a regular participant and instigator of collaborations (internal and external), working with colleagues at NIBSC, Pirbright and APHA. Her current research interests are in the development of a bilayer model of the bovine alveolus, with the aim of utilising the model to study host-pathogen interactions between bovine tuberculosis (BTB) and the alveolar epithelium. She is passionate about championing the principles of the 3Rs; Replacement, Refinement and Reduction of animals in scientific experiments.
Areas of specialism
Primary and secondary tissue culture;
Epithelial cell biology (lung and GI tract) ;
Protein purification ;
University roles and responsibilities
- Athena Swan SAT member (Vet School)
- Research Culture Committee representative
Research in my group is centred around a strategic grant (NC/M002047/1), awarded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), entitled “A bovine alveolus model to replace cattle in the study of host-pathogen interactions in bovine tuberculosis.”
BTB is a zoonosis which infects livestock and wildlife with severe socio-economic consequences and an impact on animal health. In the absence of improved control the projected economic burden to GB over the next decade is predicted to be £1 billion (http://www.defra.gov.uk/animal-diseases/a-z/bovine-tb/). Tackling BTB requires deeper insights into host-pathogen interactions otherwise it is unlikely any major breakthroughs in developing effective tools for disease intervention will occur. We aim to replace cattle in the study of BTB pathogenesis by providing a tissue culture model with which to study fundamental events following infection of the bovine lung with virulent mycobacteria that can’t be conducted currently in vitro. Our model consists of a cellular bilayer of bovine pulmonary artery endothelial cells (BPAECs) and bovine alveolar type II (immortalised and primary) cultured at an air-liquid interface on a PET porous membrane. We are using this model to test the hypothesis that a significant aspect of vaccine-mediated protection against BTB is expressed at the level of host-pathogen interactions within the alveolus.
Our project has a positive impact on animal replacement, removing the need to infect cattle with mycobacteria to answer fundamental questions in TB pathogenesis and provide a valid substitute for cattle that can be used by researchers without access to animal facilities. Vaccines against BTB developed to generate a specific host response would be a significant advance on the current situation where vaccines are tested empirically in cattle to evaluate their efficacy and identify biomarkers that might predict vaccine efficacy without challenge. A specific objective of this project is to determine whether the behaviour of BCG / M. bovis and host cells in the model correlates with the protective efficacy seen in cattle challenge studies from which we have stored PBMCs to evaluate.
- VMS1003 – Structure and Function 1
The molecular basis of genetics I - Nucleic acids and chromatin
The molecular basis of genetics II – DNA Replication
Gene Expression I and II - Transcription and Translation
- Supervision and direction of undergraduates and visiting researchers in laboratory projects.
Lee, D.F., Salguero-Bodes, F.J., Grainger, D., Francis, R.J., MacLellan-Gibson, K., Chambers, M.A. Isolation and characterisation of alveolar type II pneumocytes from adult bovine lung, Sci Rep 2018 submitted
Jones, A.M., Westwood, I.M., Osborne, J.D., Lee, D.F., McAndrew C., Jones K., Workman P., Collins I., van Montfort R.L. A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms. Sci Rep. 2016 Oct 6;6:34701. doi: 10.1038/srep34701.
Malecová, B., Caputo, V.S., Lee, D.F., Hsieh, J.J., Oelgeschläger T. Taspase1 processing alters TFIIA cofactor properties in the regulation of TFIID. Transcription. 2015;6(2):21-32. doi: 10.1080/21541264.2015.1052178.
Lee DF, Salguero FJ, Stewart GR, Vordermeier M, Chambers, MA: The use of an immortalised bovine alveolar type II (B2AE/BATII) cell line in the construction of a bilayer model of the alveolus. NC3Rs Fellows Meeting, London, 2018
Lee DF, Chambers MA: Construction and characterisation of a bilayer consisting of bovine type II alveolar epithelial (BATII) and bovine pulmonary arterial endothelial cells (BPAECs). Advances in Cell and Tissue Culture, Cardiff, 2018.
Lee DF, Chambers MA: Immortalisation and characterisation of a bovine type II alveolar epithelial (B2AE) cell line. Association for Veterinary Teaching and Research Work annual conference, 2017
Lee DF, Lethem MI and Lansley AB: A mucus-secreting in vitro cell culture model (SPOC1) for studying drug absorption [of beta-blockers] in the airways, PharmSci, Hatfield 2017
Lee DF, Salguero-Bodes FJ, Stewart GR, Vordermeier M, Chambers MA: A bovine alveolus model to replace cattle in the study of host-pathogen interactions in bovine tuberculosis (BTB). Advances in Cell and Tissue Culture Research, Manchester, 2017
Lee DF, Salguero-Bodes FJ, Stewart GR, Vordermeier M, Chambers MA: A bovine alveolus model to replace cattle in the study of host-pathogen interactions in bovine tuberculosis (BTB). Vaccinology, Belfast, 2017 Invited Speaker
Lee DF, Salguero-Bodes FJ, Stewart GR, Vordermeier M, Chambers MA: A bovine alveolus model to replace cattle in the study of host-pathogen interactions in bovine tuberculosis (BTB). NC3Rs Symposium, 2016
Smrekar K, Fox R, Lee D, Gosling M and Danahay H: Flagellin-induces a hypersecretory phenotype in primary human bronchial epithelial cells, presented at The 13th European Cystic Fibrosis Basic Science Conference, Pisa, Italy, 2016
Lansley AB, Lee DF and Lethem MI: Are respiratory cell lines proving useful in pharmaceutical development? Drug Delivery to the Lungs Conference (DDL25), The Aerosol Society, Edinburgh 2014.
Lee DF, Lansley AB, Lethem MI: The characterisation of the UNCN3T airway cell line as an in vitro model to study drug permeability in the presence of mucus (presentation and poster). PharmSci 2015, Nottingham; British Association of Lung Research, 2014, London; Doctoral College Conference, University of Brighton, 2014.
Lee DF, Lansley AB, Lethem MI: SPOC1: a secretagogue-free in vitro model to study drug permeability in the presence of mucus (presentation and poster). PharmSci 2014, Hatfield; British Association of Lung Research, 2014, London; Doctoral College Conference, University of Brighton, 2014.
Lee DF, Lansley AB, Lethem MI: The use of SPOC1 as an in vitro model to study drug permeability in the presence of mucus (presentation, poster and position on the discussion panel). PharmSci 2013, Edinburgh; Doctoral College Conference, University of Brighton, 2013.
Lee DF, Lansley AB, Lethem MI: The use of Calu-3 as an in vitro model to study drug permeability in the presence of mucus (presentation and poster – manuscript in preparation). Doctoral College Conference 2012, University of Brighton; British Association of Lung Research, 2012, Southampton, 2012.
Lee DF, Lansley AB, Lethem MI: The use of in vitro models to study drug permeability in the presence of mucus (presentation). GlaxoSmithKline Lung Symposium, Stevenage (video-link to US), 2011.
Lee DF, Oelgeschlager T: The Functional Characterisation of hsTAF5 (poster and presentation). Marie Curie Research Institute Conference, Wye, 2007.
Lee DF, Aherne, GW: The HTS of upregulation of the mis-match repair (MMR) gene MLH1 in HCT116 (poster). British Association of Cancer Research, Leeds, 2002