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Biography
Amanda Tatler is currently a Senior Research Fellow working within the Division of Respiratory Medicine at the University of Nottingham, UK. Her research focuses primarily upon on mechanisms of TGFβ-mediated tissue remodelling in the lung in the context of a variety of respiratory conditions such as asthma, pulmonary fibrosis and viral infections. More specifically her research examines how activation of TGFβ by integrins including αvβ5 and αvβ6 contributes to disease pathogenesis.
Amanda was awarded a Royal Society Travel Fellowship in 2011 allowing her to undertake a period of additional post-doctoral training in the Sheppard lab at the Lung Biology Centre, University of California San Francisco. While working at UCSF, Amanda gained invaluable experience using in vitro, in vivo and ex vivo models to investigate respiratory diseases, including a precision-cut ex vivo lung slice model and isolation of primary Type II alveolar epithelial cells from human lung. Following her return to the UK the National Centre for Replacement, Reduction and Refinement (NC3Rs) awarded her a David Sainsbury Fellowship in 2012 to further investigate the role of bronchoconstriction in promoting asthmatic airway remodelling via activation of TGFβ. As part of this fellowship, Amanda has spent 6 months at Harvard University Medical School in the US, advancing her knowledge of the ex vivo lung slice model in collaboration with Dr Ramaswamy Krishnan. Furthermore, Amanda has collaborated with Professor Thomas Meersman in the Sir Peter Mansfield MRI Centre to further develop the use of functional MRI as a tool for studying animal models of asthma, which has recently been accepted for publication in Magnetic Resonance in Medicine.
In 2015 Amanda was awarded a Joan Bending, Evelyn Bending, Mervyn Stephens and Olive Stephens Memorial Fellowship. During this fellowship Amanda will develop a novel ex vivo breathing lung slice model, which will build upon existing ex vivo lung slice models to incorporate mechanical simulation of tidal breathing and deep inspiration. Amanda aims to utilise this new model to investigate how tidal breathing and deep inspiration may affect the development of airway remodelling in asthma. This fellowship is partly funded by both the Medical Research Foundation and Asthma UK.
Additionally, Amanda has been collaborating with Dr Bindi Brook (School of Mathematics, University of Nottingham) and others to further investigate the role of bronchoconstriction and airway smooth muscle cells in the development of asthmatic airway remodelling. This has resulted in a successful 4 year MRC project grant application on which Amanda is a Co-investigator, to develop an in silico model to investigate the pathogenesis of airway remodelling.
Amanda has sat on the committee of the British Association for Lung Research (balr.co.uk) since 2010, and as Meetings Secretary since 2013. In addition, Amanda sits on the Web Committee of the American Thoracic Society Assembly of Respiratory Cell Molecular Biology, the scientific committee of the British Lung Foundation and is an active committee member on the University of Nottingham Medical School Career Development and Equality Committee. She is an active STEM Ambassador and regularly participates in activities aimed to inspire children and young adults in to careers in Science, Technology, Engineering and Maths. Furthermore, Amanda is an Associate Faculty Member for Faculty 1000, acting to peer review published scientific articles.
Expertise Summary
In vivo and ex vivo models of respiratory diseases including development of novel models to impact the 3Rs;
Molecular biology including chromatin immunoprecipitation and investigating regulation of gene expression;
Functional assays to assess activation of TGF<beta> in vitro and in vivo;
Isolation, culture and characterisation of a variety of primary cells from human and animal tissue;
Flow cytometry;
Immunohistochemistry, immunocytochemistry, immunofluorescence and histological staining
Western blotting and electrophoresis
DNA cloning and mutagenesis
Transfections including plasmids and siRNA constructs
Research Summary
* Developing a novel "breathing" lung slice model by imposing cyclic stretch on precision cut lung slices
* Investigating the role of bronchoconstriction on TGFbeta activation and the developement of asthmatic airway remodelling
* Delineating the role of Elk1 as a master regulator of fibrogenesis
Recent Publications
JENKINS RG, MOORE BB, CHAMBERS RC, EICKELBERG O, KÖNIGSHOFF M, KOLB M, LAURENT GJ, NANTHAKUMAR CB, OLMAN MA, PARDO A, SELMAN M, SHEPPARD D, SIME PJ, TAGER AM, TATLER AL, THANNICKAL VJ, WHITE ES and , 2017. An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis. American journal of respiratory cell and molecular biology. 56(5), 667-679 JOHN AE, PORTE J, JENKINS G and TATLER AL, 2017. Methods for the Assessment of Active Transforming Growth Factor-β in Cells and Tissues. Methods in molecular biology (Clifton, N.J.). 1627, 351-365 TATLER, AMANDA L., HABGOOD, ANTHONY, PORTE, JOANNE, JOHN, ALISON E., STAVROU, ANASTASIOS, HODGE, EMILY, KERAMA-LIKOKO, CHERYL, VIOLETTE, SHELIA M., WEINREB, PAUL H., KNOX, ALAN J., LAURENT, GEOFFREY, PARFREY, HELEN, WOLTERS, PAUL JOHN, WALLACE, WILLIAM, ALBERTI, SIEGFRIED, NORDHEIM, ALFRED and JENKINS, GISLI, 2016. Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin alpha v beta 6 Expression JOURNAL OF BIOLOGICAL CHEMISTRY. 291(18), 9540-9553 HABGOOD AN, TATLER AL, PORTE J, WAHL SM, LAURENT GJ, JOHN AE, JOHNSON SR and JENKINS G, 2016. Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis. Laboratory investigation; a journal of technical methods and pathology. 96(6), 623-31
Joan Bending, Evelyn Bending, Mervyn Stephens and Olive Stephens Memorial Fellowship - Oct 2015 - Mar 2019 (£300k)
NC3Rs David Sainsbury Fellowship - Oct 2012 to Sept 2015 (£195k)
Royal Society Travel Fellowship - Jan 2011 to Apr 2011 (£4k)
MRF Project Grant (PI) - Oct 2016 to Sept 2019 (£240k)
MRC Project Grant (Co-I) - Oct 2014 to Sept 2018 (£640k)