The Cystic Fibrosis Airway Research Group

Our goal is to develop an effective genetic therapy for prevention or treatment of Cystic Fibrosis airway disease.

The group’s research themes are currently focussed on several complementary areas; achieving effective lentiviral CFTR vector gene delivery, lentiviral vector development, upscaling vector production, transducing airway stem cells in situ to enable extended gene expression, developing new delivery methods, and developing rapid and accurate outcome measures for assessment of airway disease using X-ray imaging.

The lentiviral gene therapy we are developing and testing has three clear advantages:

  1. The only rational way to prevent or halt CF airway disease is by overcoming the fundamental problem – the defective CF gene – by adding a correct copy of the CF gene to airway cells.
  2. Successful correction will be effective for all CF mutations (of which there are more than 2,000), in contrast to new and expensive drugs that depend on specific CF mutation type, this cure would be suitable for all CF patients.
  3. Effective gene treatment of airway stem cells – the cells naturally present in the airway that are responsible for repair and renewal of airway tissue – will provide very long-lived correction after the initial dosing is completed, with a goal of seeking lifelong correction for the patient.

The need for fast, reliable, and non-invasive methods to pre-clinically test for correction of CF airway physiological function has led to rapid progress using novel synchroton X-ray imaging approaches in live mice in collaboration with physicists from Monash University. These techniques quantify the effects of treatments on airway surface function (including mucociliary transit), as well as the local airflow in the lungs during breathing.

Research into translation of methods for potential human application in a non-synchroton diagnostic setting is continuing in studies performed at the Imaging and Medical Beamline at the Australian Synchroton, and the Munich Compact Light Source. We now have access to a new National Imaging Facility funded 4Dx Permetium machine located at the SAHMRI Pre-clinical Imagine and Research Laboratory in Adelaide.

Further information:

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  • Research

    Gene therapy research results

    Reporter gene expression

    mouse nasal airway

    Image of mouse nasal airway LacZ staining (blue cells) on treated (right) side. S =nasal septum. This study demonstrated the efficiency with which our vector can transduce the appropriate cells within the nasal airway of live mice.

    ferret lung airways

    This pilot study was designed to determine whether our gene vector delivery protocol is effective in normal ferret lung airways, prior to consideration of studies in CF ferrets. These results verify that our gene vector delivery protocol can produce airway reporter gene transfer in normal ferret trachea. The blue dots are cells that express the LacZ gene. Histology verified that ciliated, non-ciliated and basal cells were transduced in the tracheal epithelium.

    Luciferase gene expression

    Luciferase gene expression is evident in the nose and lung airways following a nasal administration of our lentiviral vector carrying the luciferase reporter gene. Luciferase gene expression is enhanced in the nasal airways of mice that received a) surface enhancing pre-treatment compared to b) PBS pre-treatment.

    Therapeutic CFTR expression

    CFTR defect in CF mice

    Significant partial correction of the CFTR defect in CF mice was persistent for 12 months following a single treatment with our lentiviral vector carrying the therapeutic CFTR gene. No other group, worldwide, can achieve this longevity of functional expression.

    Airway imaging research results

    High-resolution imaging

    visualise microscopic structures
    visualise microscopic structures

    Renderings of high-resolution synchrotron computed tomographic images can be used to visualise microscopic structures within a whole animal. This data was collected during experiments at the SPring-8 Synchrotron.

    Mucociliary clearance

    mucociliary clearance

    Mucociliary clearance in the nose and lungs of live mice can be tracked using synchrotron phase contrast X-ray imaging. Here the effect of hypertonic saline - a clinically used treatment for CF lung disease - can be seen on the clearance of deposited marker particles.

    Fluid dosing in the nose and lungs

    movement of fluid
    movement of fluid

    These images show the movement of fluid (a surrogate for our gene vector) in the nose and lungs of live mice.

    airway imaging experiments

    The group recently performed airway imaging experiments at the recently commissioned Imaging and Medical Beamline at the Australian Synchrotron in Melbourne. Their goal is to develop novel visualisation strategies for respiratory disease. Airways of several animal species were imaged. Here a 3D visualisation of rat anatomy is shown in exquisite detail. Rendering was performed by Dr Anton Maksimenko from the Australian Synchrotron.

    mouse nasal airway

    Early data from our latest 2012 SPring-8 studies shows a new ability to image the area of mouse nasal airway relevant to future studies for CFTR gene transfer. We can now discern differences in mucociliary clearance following aerosol treatments.

    hypertonic saline

    The effects of hypertonic saline and mannitol on clearance are shown.

    Latest developments

     

    bronchoscopic dosing

    For respiratory research utilising gene vector delivery to the lung, the size of rodent models has typically necessitated relatively “blind” dosing via the nose, via an endotracheal tube, or through a surgical incision into the trachea. This commonly results in a limited ability to reliably dose specific small regions of lung, and contributes to high levels of transduction variability between animals. We have designed and successfully implemented the first reliable targeted gene vector dosing of small regions in rat lungs using a miniature rigid bronchoscope containing a working channel. This method is now published in Human Gene Therapy methods. An example of bronchoscopic dosing into a CF rat lung is shown above.

    live pig airway

    The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed to be the world’s widest synchrotron x-ray beam, partly to enable clinical imaging and therapeutic applications for humans, as well as for imaging large animal models. We recently performed the first live large animal x-ray phase contrast imaging using this facility. We measured the mucociliary transport behaviour of deposited marker particles in the trachea of live anaesthetised pigs, and in one animal we performed whole-animal high resolution CT. Examples of particles moving along the live pig airway surface are shown above.

    lung disease

    We have previously established a method for examining and quantifying regional lung function deficits in vivo. The process, known as 4DXV combines four-dimensional computed tomography using phase-contrast x-ray imaging with x-ray velocimetry enables us to make local measurements of airflow through the airway tree and regional lung lobes. The image below shows the results from β-ENaC mice, a well-established mode of cystic fibrosis-like disease, and their healthy littermates. We have shown that it is possible to identify the location of lung disease.

    glass microspheres

    In 2013B SPring-8 studies (left) we have demonstrated the use of glass microspheres as suitable particles for tracking MCT in the nasal airway of CF and normal mice. In 2014A studies (right) we extended this method to the trachea of normal mice. The particles are moved by beating cilia on the airway surface, allowing us to assess the effectiveness of this biological process, and how it changes with treatment. Images ~1.2mm high.

    environmental lead dust

    In 2014A studies at SPring-8 Synchrotron in Japan we examined the MCT behaviour of real environmental lead dust (< 50 µm particle size) collected from around Port Pirie. Image is ~1.2 mm high. Here dust can be seen preferentially moving toward the dorsal surface of the trachea. Dust motion is only visible in the moving images due to the phenomemon known as "motion popout"

    Medical Beamline

    In 2015-1 studies at the Australian Synchrotron Imaging and Medical Beamline we examined the MCT behaviour of 100 µm particles in segments of excised sheep trachea. Image is ~14 mm high. These studies were performed with a future view to examining MCT in CF pig and CF ferret airways, to quantify the effect of pharmaceutical and genetic therapies in new CF animal models.

  • Patient story

    Meet five-year-old Ella

    Ella

    Ella suffers from cystic fibrosis (CF) and must undergo a daily regimen of physiotherapy to maintain her lung capacity and slow damage to her organs. This includes chest and upper abdomen patting, bubble peps, peri peps, and inhalation of hypertonic saline solution through a ventilated mask.

    Ella also takes up to 30 capsules a day containing digestive enzymes that help her body absorb fat every time she has a meal or snack. Her condition brings about recurring chest infections that often require 8-hourly doses of antibiotics for weeks at a time. It is these infections that often lead to lung transplants in CF patients by late adolescence.

    Researchers at the Adelaide Cystic Fibrosis Gene Therapy Group are working to help Ella and other children like her by correcting the basic cellular defect that causes CF lung disease. By inserting healthy genes into the defective, disease-causing cells that line the airways, they hope to correct the faulty genetic information that gives rise to respiratory illness.

    This technology has the potential to cure CF lung disease and increase the life expectancy of CF sufferers. If successful, it will also help Ella achieve two of her childhood dreams: to become a doctor and learn karate.

    We need your help to further this exciting innovation.

    Please donate here to make a difference to Ella and the lives of other children with Cystic Fibrosis.

  • Facilities

    The Allan Scott CF Research Laboratory

    The Allan Scott CF Research Laboratory

    Our 250 m2 CF research laboratory was opened in 2012 at a cost of more than $1.5M, and was funded by a partnership between the Cure4CF Foundation and the Women's and Children's Hospital Foundation. The laboratory is named in memory of the late Allan Scott - who generously donated $500,000 for construction - and is located in the Gilbert Building at the Women's and Children's Hospital within the Department of Respiratory and Sleep Medicine. The laboratory is fully equipped for the design and production of gene vectors, as well as performing all the molecular and histological assays associated with the experiments performed by the group.

    The SPring-8 Synchrotron

    The SPring-8 Synchrotron

    Many of our X-ray imaging studies demand extremely coherent/monochromatic X-rays that can currently only be produced using a synchrotron, particularly at long beamlines such as the Biomedical Imaging beamlines at the SPring-8 Synchrotron located in Hyogo Prefecture, Japan. Our group typically performs imaging experiments twice a year at SPring-8. Picture: Wikipedia.

    The Australian Synchrotron

    The Australian Synchrotron

    Picture: Wikipedia.

    The Australian Synchrotron Imaging and Medical Beamline (IMBL) was completed early in 2013, and is suitable for some of our X-ray imaging studies. The IMBL offers high-resolution, phase-contrast x-ray imaging of biomedical samples, including live animal imaging. The beamline is 150 metres long, with a satellite building that will later include a medical suite for clinical research as well as extensive support facilities for biomedical and clinical research programs. We have now performed multiple live animal imaging experiments at the IMBL, resulting in a number of publications.

  • Contacts

    Who we are

    Cystic Fibrosis Airway Research Group staff

    Left to right: Dr Trish Cmielewski, Dr Martin Donnelley, A/Prof David Parsons, Alexandra MaCarron, Nikki Reyne, Dr Nigel Farrow, Chantelle Carpentieri, Dr Juliette Delhove, Mark Gardner, Bernadette Boog and Dr Nathan Rout-Pitt

    Cystic Fibrosis Airway Research Group staff

    Left to right: Dr Martin Donnelley, Rhiannon Murrie, Richard Carnibella, A/Prof David Parsons, A/Prof Andreas Fouras, Nigel Farrow, Dr Kaye Morgan. Absent Dr Karen Siu.

    Photo taken at the BL20XU beamline at SPring-8 Synchrotron, Japan.

    Director

    A/Prof David Parsons
    +61 (0)8 816 17004
    david.parsons@adelaide.edu.au / david.parsons@health.sa.gov.au

    Associate Professor David Parsons is the Cystic Fibrosis Airway Research Group (CFARG) Director. He is a Chief Medical Scientist in the Department of Respiratory And Sleep Medicine at the Women's and Children's Hospital, a Robinson Research Institute Research Leader, and an Affiliate Senior Lecturer  at the University of Adelaide Medical School. He has devoted the past 23 years to finding a cure for Cystic Fibrosis airway disease, has twice-won Service Excellence Awards, and recently led the CFARG team to a shared Award for his innovations in respiratory research and testing at the Women's and Children's Hospital. He was recognised as a fellow of the ANZSRS in 2015, and received their research medal in the same year.

    He and his research team have pioneered a ground-breaking gene therapy technique that has been successful in reversing the basic cellular defect that causes CF in mouse models, showing the clear potential for gene-addition therapy as a long-lasting treatment for CF lung disease. David was also responsible for initiating leading-edge research into the surface behaviour of airways in health and disease using non-invasive synchrotron X-ray imaging techniques. In collaborations with Monash University colleagues starting in 2015 he has assisted them (and more recently in their new roles in the Australian startup company 4Dx.com) with developing a revolutionary lung motion imaging technique to assess CF lung disease.  This technology is now undergoing FDA assessment for approval for human use.

    In related work, by monitoring the depth of the airway surface liquid (ASL) and the transit of microscopic particles previously considered too small to view in living airways, David and the team hope are able to measure the level of success of new airway treatments. This approach is being applied to assessing the effectiveness of the  gene-addition therapy that is planned for future use in CF patients. More recently David led development of novel methods for precision lung lobe dosing in rats by adapting an endoscope used in humans to use in rat lungs. The combination of precision dosing with the new method of local-region assessment of lung function changes the group has new and powerful tools to assist in CF lung treatment developments.

    David's creation and development of CF airway gene transfer methods were supported initially by the USA CF Foundation, and have evolved to attract funding from State and National funding bodies, including the National Health and Medical Research Council in Australia, the Fay Fuller Foundation SA, the Gandel Foundation in Victoria, and the Cure 4 Cystic Fibrosis Foundation.

    Co-Director

    Dr Martin Donnelley
    +61 (0)8 816 19181
    martin.donnelley@adelaide.edu.au

    Dr Martin Donnelley is a Senior Research Fellow at the University of Adelaide, and the Co-Director of the Cystic Fibrosis Airway Research Group. He trained as a Biomedical Engineer and completed a PhD in Medical Image Processing at Flinders University in 2008. Martin joined the group in 2007 as a post-doctoral researcher on an NHMRC grant.

    He has spent the last ten years developing gene therapy methodologies, as well as technologies for the measurement of in vivo dynamic airway function in animal models. His key achievements lie in the area of non-invasive synchrotron imaging of respiratory processes at scales that have not previously been possible in vivo. He developed a novel non-invasive airway health assessment method based on using synchrotron imaging to track changes in the mucociliary transit (MCT) behaviour of deposited marker particles following pharmaceutical treatments. This work is linked to studies he performed with collaborator Dr Kaye Morgan from Monash University, that show they can also measure changes in airway surface liquid (ASL) depth in live anaesthetised mouse airways. They have now combined these methods into a single powerful airway health assessment method.

    In 2016 he and collaborators from Monash University published the first demonstration of the use of X-ray based pulmonary function testing for the quantification of lung disease heterogeneity in B-ENaC mice. This imaging method gathers lung motion information during normal breathing, and has revolutionary potential since it can detect, quantify and follow changes in regional lung function over time. In 2017 he championed the development of an Adelaide-based CF rat model using CRISPR/Cas9 gene editing, to facilitate further development of the group's airway gene therapy.

    Postdoctoral Scientists

    Dr Trish Cmielewski
    +61 (0)8 816 16430
    patricia.l.cmielewski@adelaide.edu.au

    Dr Trish Cmielewski gained a BSc in Biology at Flinders University of SA and her early career saw her employed in a wide range of disciplines including Anaesthesia and Intensive Care, Pain Management, Histopathology and Gastroenterology. In 2001 Trish began working as a Medical Scientist with the Department of Respiratory and Sleep Medicine at the Women's and Children's Hospital, Adelaide, South Australia.

    Trish has considerable experience in both clinical and experimental aspects of medical research and completed a PhD in lentiviral airway gene therapy for the treatment of cystic fibrosis in a mouse model. Trish's research is currently focussed on improving our therapeutic CFTR gene vector into both rodent models of CF. She is also the Manager of the Cystic Fibrosis Airway Research Group’s Allan Scott Laboratory.

    Dr Nigel Farrow
    +61 (0)8 816 19183
    nigel.farrow@adelaide.edu.au

    Dr Nigel Farrow gained a BMSc in molecular biology and genetics from Flinders University, South Australia in 2009 and a BHSc (Hons) from The University of Adelaide School of Medicine in 2010. Nigel joined the Adelaide Cystic Fibrosis Airway Research Group in 2010 for his Honours project, and has remained with the group, completing a PhD in 2014. Nigel has a research interest in gene therapy for cystic fibrosis focusing on endogenous respiratory stem cells and their role in sustained transgene expression. Nigel is also investigating the impact on increasing transgene expression by multiple vector dosing strategies and its impact on the immune system in an animal model.

    Dr Nathan Rout-Pitt
    nathan.rout-pitt@adelaide.edu.au

    Dr Nathan Rout-Pitt completed a BSc in molecular biology at Flinders University, as well as honours in molecular aquaculture before moving to the University of Adelaide to undertake his PhD. Nathan’s work during his PhD focused on mesenchymal stem cells and gene therapy. During this work he used the same lentiviral vector used by the Cystic Fibrosis Airway Research Group, and due to this expertise Nathan joining the group in late 2015.

    Nathan is now responsible for overseeing the CF Airway Research Group’s plasmid and lentiviral vector production needs, and has recently increased the group’s production capacity through the development of a method for upscaling adherent LV vector production. Nathan is also interested in understanding the stem cell niche within the lungs, and determining whether we can target stem cells with LV vector, administer normal cells to populate the lungs with CFTR functional cells, or modulate the stem cells to reduce the fibrosis effects that are responsible for lung damage.

    Dr Juliette Delhove
    juliette.delhove@adelaide.edu.au

    Dr Juliette Delhove completed her Bachelor of Science degree in South Africa at the University of Cape Town in 2008. She specialised in biochemistry, genetics and development, and was awarded a Medical Honours degree in human genetics the following year. Subsequently, she studied at Imperial College London in the UK where she obtained a Masters degree in human molecular genetics. This lead to a collaboration between Queen Mary’s University of London and University College London where she worked as a research assistant developing biosensing lentiviral reporters. These were utilized to non-invasively monitor biological pathways in vivo with the aim of reducing the number of animals required for experimentation.

    Concurrently, Juliette was enrolled as a PhD student at the University of the Witwatersrand, in collaboration with St. George’s University of London. Her project evaluated the temporal signalling profiles of key biological pathways during the development of liver disease. In 2016 she was employed at the Great Ormond Street Institute of Child Health were she was part of a consortium focused on developing a packaging cell line for large scale lentiviral production. In 2017, she relocated to Australia and is now a part of the Cystic Fibrosis Airway Research Group where she will be utilising her skills to develop and optimise lentiviral vectors for use in gene therapy for cystic fibrosis.

    Postgraduate Students

    Alexandra McCarron
    alexandra.mccarron@student.adelaide.edu.au

    Project: Upscaling lentivirus production for use in pre-clinical airway gene therapy studies
    Ali joined the Cystic Fibrosis Research Group for her Bachelor of Health Science Honours project in 2015, after completing her undergraduate degree in Bachelor of Animal Science. During her undergraduate degree Ali become interested in the use of animal models to study human diseases and how animals can play a significant role in the establishment of disease treatments which led to her honours project. In 2016 Ali started a PhD with the group. Her project aims to modify lentivirus production methods, including the use of bioreactor technology, to produce larger quantities of vector, and to reduce the immunogenicity of the vector preparation to improve the success of repeat administration.

    Chantelle Carpentieri
    chantelle.carpentieri@adelaide.edu.au

    Project: Assessment of Airway Conditioning Compounds for Improving Cystic Fibrosis Airway Gene Therapy
    Chantelle joined the Cystic Fibrosis Airway Research Group in 2016. The aim of her honours project was to assess whether pseudotyping LV vector with HA results in stronger gene expression than VSV-G, whether it transduces basal stem cells, and whether the use of LPC conditioning results in extended persistence or improved basal stem cell targeting. In 2018 Chantelle started a PhD with the group. Her project aims to demonstrate the benefits of pre-conditioning for airway gene therapy, by investigating the effectiveness and safety of LPC and other alternative conditioning compounds on gene expression levels in cell culture and relevant animal models.

    Nikki Reyne
    nikki.reyne@adelaide.edu.au

    Project: Assessing the efficacy of airway gene therapy in a new Australian cystic fibrosis rat model
    Nikki completed a Bachelor of Animal Science at The University of Adelaide, and spent 8 years working in animal laboratories. In 2018 Nikki joined Cystic Fibrosis Airway Research Group as a Research Assistant. Her role primary involves overseeing the CF rat colony and assisting with rat procedures. In mid-2019 Nikki started her honours project with the group. Her project aims to optimise nasal potential difference procedures in rats and then assess CFTR function after delivery of lentiviral vector CFTR to the nose of CF rats.

    Administrative Staff

    Bernadette Boog
    +61 (0)8 816 17241
    bernadette.boog@adelaide.edu.au

    Bernadette is responsible for administrative support and management of the Gene Therapy research group. Her role involves management of financial cost centres, coordinating grant funding applications, OGTR, Biosafety, Ethics annual reports & business plans and maintaining strong collaborative relationships with hospital-based departments and external organizations. This role is an essential part of the CF Gene Therapy Research group bringing administrative continuity to this group of leading edge, globetrotting research scientists.

    Affiliates

    Dr Greg Smith
    +61 (0)8 816 17008
    greg.smith2@health.sa.gov.au

    Dr Smith is a clinical respiratory specialist and allergist in the Respiratory and Sleep Medicine Department and part of the CF Clinic team at the WCH. He joined the CF Research Team in 2004, and provides practical experience and advice around the clinical development of CF airway gene therapy and technique training (e.g. bronchoscopic vector delivery). This important experimental-clinical interface assists research to relate to CF patient needs, assisting in the design and analysis of the animal model studies. His input is invaluable as we move towards translation of pre-clinical gene therapy protocols into human clinical trials.

    Collaborators

    University of North Carolina: Prof Richard Boucher
    Monash University: Dr Karen Siu, A/Prof Andreas Fouras, Dr Kaye Morgan, A/Prof Anne Chidgey
    Melbourne University: A/Prof Ivan Bertoncello
    University of Western Australia: A/Prof Yuben Moodley, A/Prof Anthony Kicic
    SAHMRI: Dr Tim Kuchel
    UniSA: A/Prof Albert Juhasz, Dr Euan Smith, Dr Darren Miller, Dr Ivan Lee
    SA Pathology: Dr Chantelle McIntyre

  • Publications

    • J. Delhove, I. Osenk, I. Prichard, M. Donnelley, “Acceptability of gene therapy: A systematic review”, Human Gene Therapy, Accepted for publication, 2019.
    • R. Murrie, F. Werdiger, M. Donnelley, Y. Lin, R. Carnibella, C. Samarage, I. Pinar, M. Preissner, J. Wang, J. Li, K. Morgan, D. Parsons, S. Dubsky, A. Fouras, “Real time in-vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory x-ray source”, Scientific Reports, Accepted for publication, 2019.
    • K. Morgan, D. Parsons, P. Cmielewski, A. McCarron, R. Gradl, N. Farrow, K. Siu, A. Takeuchi, Y. Suzuki, K. Uesugi, M Uesugi, N. Yagi, C. Hall, M. Klein, A. Maksimenko, A. Stevenson, D. Hausermann, M. Dierolf, F. Pfeiffer, M. Donnelley, “Methods for dynamic synchrotron X-ray respiratory imaging of live animals”, Journal of Synchrotron Radiation, vol. 27, pp. 164-75, 2019.
    • K. Morgan, R. Gradl, M. Dierolf, C. Jud, B. Günther, F. Werdiger, M. Gardner, P. Cmielewski, A. McCarron, N. Farrow, H. Haas, M. Kimm, L. Yang, D. Kutschke, T. Stoeger, O. Schmid, K. Achterhold, F. Pfeiffer, D. Parsons, M. Donnelley, “In vivo x-ray imaging of the respiratory system at conventional and compact synchrotrons”, Proc. SPIE 11113, Developments in X-Ray Tomography XII, 111130G, 2019.
    • L. Yang, R.Gradl, M. Dierolf, W. Möller, D. Kutschke, A. Feuchtinger, L. Hehn, M. Donnelley, B. Günther, K. Achterhold, A. Walch, T. Stoeger, D. Razansky, P. Pfeiffer, K. Morgan,O. Schmid, “Multimodal precision imaging of pulmonary nanoparticle delivery in mice: Dynamics of application, spatial distribution, and dosimetry”, Small, vol. 15(49), 2019.
    • F. Kastury, E. Smith, E. Lombi, M. Donnelley, P. Cmielewski, D. Parsons, K. Scheckel, A. Kingston, G. Myers, D. Paterson, M. de Jonge, A. Juhasz, “Dynamics of lead bioavailability in indoor dust and spectroscopic investigation of the link between ingestion and inhalation pathways”, Environmental Science & Technology, vol. 53(19), pp. 11486-11495, 2019.
    • S. Kedzior, T. Bianco-Miotto, J. Breen, K. Diener, M. Donnelley, K. Dunning, M. Penno, A. Rumbold, J. Schjenken, D. Sharkey, N. Hodyl, T. Fullston, M. Gardiner, H. Brown, “It takes a community to conceive: An analysis of the scope, nature and accuracy of online sources of health information for couples trying to conceive”, Reproductive Biomedicine and Society Online, Accepted for publication, 2019.
    • F. Kastury, E. Smith, E. Doelsh, E. Lombi, M. Donnelley, P. Cmielewski, D. Parsons, K. Scheckel, D. Paterson, M. de Jonge, C. Herde, A. Juhasz, “In-vitro, in-vivo and spectroscopic assessment of lead exposure reduction via ingestion and inhalation pathways following immobilization using phosphorus and iron amendments”, Environmental Science & Technology, vol. 53(17), pp. 10329-41, 2019.
    • M. Gardner, A. McCarron, K. Morgan, D. Parsons, M. Donnelley, “Particle coating alters mucociliary transit in excised rat trachea: A synchrotron X-ray imaging study”, Scientific Reports, vol. 9, 10983, 2019.
    • R. Gradl, M. Dierolf, L. Hehn, B. Günther, W. Möller, D. Kutschke, L. Yang, T. Stoeger, B. Gleich, K. Achterhold, M. Donnelley, F. Pfeiffer, O. Schmid, K. Morgan, “Visualising respiratory treatment delivery and deposition using x-ray imaging”, Journal of Controlled Release, vol. 307, pp. 282-291, 2019.
    • A. McCarron, M. Donnelley, McIntyre, D. Parsons, “Transient lentiviral vector production using a packed-bed bioreactor system”, Human Gene Therapy Methods, vol. 30(3), 2019.
    • H. Jung, S. Lee, M. Donnelley, D. Parsons, I. Lee, V. Stamatescu, “Multiple marker particle tracking in Synchrotron time-lapse X-ray images for assessment of mucociliary clearance in live mouse nasal airways”, Pattern Recognition, vol. 93, pp. 485-497, 2019.
    • Z. Wang, J. Cai, W. Guo, M. Donnelley, D. Parsons, I. Lee, “Backprojection Wiener Deconvolution for Computed Tomographic Reconstruction”, PLOS ONE, 13(12): e0207907, 2018.
    • M. Donnelley, D. Parsons, “Gene therapy for cystic fibrosis lung disease: Overcoming the barriers to translation to the clinic”, Frontiers in Pharmacology, section Pharmacology of Ion Channels and Channelopathies, vol. 9(1381), 2018.
    • M. Donnelley, M. Klein, D. Hausermann, C. Hall, A. Maksimenko, K. Morgan, D. Parsons, “Live pig airway surface imaging and whole-animal CT at the Australian Synchrotron Imaging and Medical Beamline”, Journal of Synchrotron Radiation, vol. 26, 2018.
    • R. Gradl, M. Dierolf, L Hehn, B. Gunther, D. Kutschke, L. Yang, W. Moller, T. Stoeger, M. Kimm, H. Haas, N. Roiser, D. Pfeiffer, M. Donnelley, C. Jud, B. Gleich, D. Parsons, K. Achterold, O. Schmid, F. Pfeiffer, K. Morgan, “Dynamic X-ray Imaging at the Munich Compact Light Source”, Proceedings of Microscopy & Microanalysis, vol. 24(s2), pp. 352-353, 2018.
    • N. Rout-Pitt, N. Farrow, D. Parsons, M. Donnelley, “Epithelial-Mesenchymal Transition (EMT): A universal process in lung diseases with implications for cystic fibrosis patients”, Respiratory Research, 2018.
    • C. McIntyre, M. Donnelley, N. Rout-Pitt, D. Parsons, “Lobe-specific gene vector delivery to rat lungs using a miniature bronchoscope”, Human Gene Therapy, Accepted for publication, 2018.
    • N. Farrow, P. Cmielewski, M. Donnelley, N. Rout-Pitt, Y. Moodley, I. Bertoncello, D. Parsons, “Epithelial disruption: A new paradigm enabling human airway stem cell transplantation”, Stem Cell Research and Therapy, Accepted for publication, 2018.
    • R. Gradl, M. Dierolf, B. Gunther, L. Hehn, W. Moller, D. Kutscheke, L. Yan, M. Donnelley, R. Murrie, A. Erl, T. Stoeger, B. Gleich, K. Achterhold, O. Schmid, F. Pfeiffer, K. Morgan, “In-vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source”, Scientific Reports, vol. 8, 6788, 2018.
    • A. McCarron, D. Parsons, M. Donnelley, “Airway disease phenotypes in animal models of cystic fibrosis”, Respiratory Research, vol. 19:54, 2018.
    • N. Rout-Pitt, A. McCarron, C. McIntyre, M. Donnelley, D. Parsons, “Upscaling the production of a VSV-G pseudotyped lentiviral vector using cell factories”, Journal of Biological Methods, vol. 5(2):e90, 2018.
    • N. Farrow, M. Donnelley, P. Cmielewski, N. Rout-Pitt, C. McIntyre, I. Bertoncello, D. Parsons, “The role of basal cells in producing persistent lentivirus-mediated airway gene expression”, Human Gene Therapy, vol. 29(6), pp. 653-662, 2018.
    • A. McCarron, M. Donnelley, D. Parsons, “Scale-up of lentviral vectors for gene therapy: advances and challenges”, Cell and Gene Therapy Insights, 2017.
    • P. Cmielewski, N.Farrow, S. Devereux, D. Parsons, M. Donnelley, “Gene therapy for Cystic Fibrosis: Improved delivery techniques and conditioning with lysophosphatidylcholine enhance lentiviral gene transfer in mouse lung airways”, Experimental Lung Research, vol. 43(9-10), pp. 426-433, 2017.
    • M. Donnelley, M. Awadalla, K. Morgan, N. Farrow, C. Hall, D. Parsons, “Measuring mucociliary clearance activity in live excised large animal trachea at the Australian Synchrotron Imaging and Medical Beamline”, Respiratory Research, vol. 18:95, 2017.
    • H. Jung, I. Lee, S. Lee, D. Parsons, M. Donnelley, “Multiple mucociliary transit marker tracking in synchrotron X-ray images using the global nearest neighbour method”, IEEE Conference Proceedings, Accepted for publication, 2017.
    • H. Jung, I. Lee, S. Lee, M. Donnelley, D. Parsons, “Automated detection of circular marker particles in synchrotron phase contrast x-ray images of live mouse nasal airways for cystic fibrosis therapy assessment", Expert Systems with Applications, vol. 73, pp. 57-68, 2017.
    • A. McCarron, M. Donnelley, C. McIntyre, D. Parsons, "Challenges of up-scaling lentivirus production and processing”, Journal of Biotechnology, vol. 240, pp. 23-30[MD1] , 2016.
    • K. Morgan, T. Petersen, M. Donnelley, N. Farrow, D. Parsons, D. Paganin, “Capturing and visualizing transient x-ray topological features by single-grid phase imaging”, Optics Express, vol. 24(21) pp. 24435-24450, 2016.
    • M. Donnelley, K. Morgan, N. Farrow, R. Carnibella, R. Murrie, A. Fouras, D. Parsons, “Alteration of Mouse Nasal Airway Surface Mucociliary Transit by Airway Rehydrating Agents”, SPring-8 Research Reports, Accepted for publication, 2016.
    • C. Stahr, C. Samarage, D. Parsons, M. Donnelley, N. Farrow, K. Morgan, G. Zosky, R. Boucher, K. Siu, S. Dubsky, A, Fouras, “Quantification of heterogeneity in lung disease with image-based pulmonary function testing”, Scientific Reports, vol. 6, 2016.
    • M. Donnelley, K. Morgan, K. Siu, N. Farrow, D. Parsons, “Non-Invasive Airway Health Measurement Using Synchrotron X-Ray Microscopy of High Refractive Index Glass Microbeads”, AIP Conf. Proc. vol. 1696, 020011, 2016.
    • R. Murrie, K. Morgan, A. Maksimenko, A. Fouras, D. Paganin, C. Hall, K. Siu, D. Parsons, M. Donnelley, Live small animal x-ray lung velocimetry and lung micro-tomography at the Australian Synchrotron Imaging and Medical Beamline, Journal of Synchrotron Radiation, vol. 22, 2015.
    • Cmielewski, P., Donnelley, M. & Parsons, D.W. Long-term therapeutic and reporter gene expression in lentiviral vector treated cystic fibrosis mice. J Gene Med 16, 291-299 2014.
    • P. Cmielewski, M. Donnelley, N. Farrow, C. McIntyre, J. Penny-Dimri, T. Kuchel, D. Parsons, Transduction of Ferret Airway Epithelia by a Lentiviral Gene Vector, BMC Pulmonary Medicine 14, 183 2014.
    • K. Morgan, M. Donnelley, N. Farrow, A. Fouras, R. Boucher, N. Yagi, Y. Suzuki, A. Takeuchi, K. Useugi, K. Siu, D. Parsons, In vivo vertilization of airway surface liquid: monitoring hydration improvement in the assessment of CF treatments, American Journal of Respiratory and Critical Care Medicine, Vol. 190, pp 469-472, 2014.
    • M. Donnelley, K. Morgan, K. Siu, A. Fouras, N. Farrow, R. Carnibella, D. Parsons, Tracking extended mucociliary transport activity of individual deposited particles: Longitudinal synchrotron imaging in live mice, Journal of Synchrotron Radiation, Vol. 21, (2014).
    • M. Donnelley, K. Morgan, K. Siu, N. Farrow, C. Stahr, R. Boucher, A. Fouras, D. Parsons, Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo, Scientific Reports, 4, 3689, (2014).
    • Morgan, K.S., Donnelley, M., Paganin, D.M., Fouras, A., Yagi, N., Suzuki, Y., Takeuchi, A., Uesugi, K., Boucher, R.C., Parsons, D.W. & Siu, K.K. Measuring airway surface liquid depth in ex vivo mouse airways by x-ray imaging for the assessment of cystic fibrosis airway therapies, PLoS One 8, e55822 (2013).
    • Farrow, N., Miller, D., Cmielewski, P., Donnelley, M., Bright, R. & Parsons, D.W. Airway gene transfer in a non-human primate: Lentiviral gene expression in marmoset lungs, Scientific Reports 3, 1287 (2013).
    • Donnelley, M., Morgan, K.S., Siu, K.K. & Parsons, D.W. Variability of In Vivo Fluid Dose Distribution in Mouse Airways Is Visualized by High-Speed Synchrotron X-Ray Imaging, Journal of Aerosol Medicine and Pulmonary Drug Delivery (2013).
    • Morgan, K.S., Paganin, D.M., Parsons, D.W., Donnelley, M., Yagi, N., Uesugi, K., Suzuki, Y., Takeuchi, A. & Siu, K.K.W. Single Grating X-Ray Imaging For Dynamic Biological Systems. International Workshop on X-Ray and Neutron Phase Imaging with Gratings 1466, 124-129 (2012).
    • Donnelley, M., Siu, K.K., Jamison, R.A. & Parsons, D.W. Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways, Gene Therapy 19, 8-14 (2012).
    • Donnelley, M., Morgan, K., Siu, K.K.W. & Parsons, D.W. Dry deposition of pollutant and marker particles onto live mouse airway surfaces enhances monitoring of individual particle mucociliary transit behaviour, Journal of Synchrotron Radiation 19, 551-558 (2012).
    • Liu, C., Wong, E., Miller, D., Smith, G., Anson, D. & Parsons, D. Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges, Journal of Gene Medicine 12, 647-658 (2010).
    • Donnelley, M., Parsons, D., Morgan, K. & Siu, K. Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging. 6th International Conference on Medical Applications of Synchrotron Radiation 1266, 30-34 (2010).
    • Donnelley, M., Parsons, D., Morgan, K. & Siu, K. Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging. AIP Proceedings 1266, 30-34 (2010).
    • Donnelley, M., Morgan, K., Skinner, W., Suzuki, Y., Takeuchi, A., Uesugi, K., Yagi, N., Siu, K. & Parsons, D. A new technique to examine individual particle and fibre deposition and transit behaviour on live mouse trachea, Journal of Synchrotron Radiation 17, 719-729 (2010).
    • Cmielewski, P., Anson, D.S. & Parsons, D.W. Lysophosphatidylcholine as an adjuvant for lentiviral vector mediated gene transfer to airway epithelium: effect of acyl chain length, Respiratory Research 11, 84 (2010).
    • Stocker, A.G., Kremer, K.L., Koldej, R., Miller, D.S., Anson, D.S. & Parsons, D.W. Single-dose lentiviral gene transfer for lifetime airway gene expression, Journal of Gene Medicine 11, 861-867 (2009).
    • Morgan, K., Paganin, D., Parsons, D., Donnelley, M., Yagi, N., Uesugi, K., Suzuki, Y., Takeuchi, A. & Siu, K. Optimising Coherence Properties for Phase Contrast X-Ray Imaging (PCXI) to Reveal Airway Surface Liquid (ASL) as an Airway Health Measure. IFMBE Proceedings, World Congress on Medical Physics and Biomedical Engineering 25/II, 135-138 (2009).
    • Donnelley, M., Morgan, K.S., Fouras, A., Skinner, W., Uesugi, K., Yagi, N., Siu, K.K.W. & Parsons, D.W. Real-time non-invasive detection of inhalable particulates delivered into live mouse airways, Journal of Synchrotron Radiation 16, 553-561 (2009).

    Recent conference posters

    2019

    North American Cystic Fibrosis Conference - Nashville, USA

    Australasian Cystic Fibrosis Conference - Perth

    Thoracic Society of Australia and New Zealand - Gold Cost

    American Society of Gene and Cell Therapy - Washington, USA

    2018

    North American Cystic Fibrosis Conference - Denver, USA

    Thoracic Society of Australia and New Zealand (Adelaide)

    American Society of Gene and Cell Therapy - Chicago, USA

    2017

    North American Cystic Fibrosis Conference - Indianapolis, USA

    Australasian Cystic Fibrosis Conference - Melbourne

    Australian Gene and Cell Therapy Society - Sydney

    American Society of Gene and Cell Therapy - New Orleans, USA

    Thoracic Society of Australia and New Zealand (Canberra)

    2016

    North American Cystic Fibrosis Conference - Orlando, USA

    American Society of Gene and Cell Therapy - Washington, USA

    2015

    Medical Applications of Synchrotron Radiation - Grenoble, France

    North American Cystic Fibrosis Conference - Phoenix, USA

    Australian Cystic Fibrosis Conference - Sydney

    American Society of Gene and Cell Therapy - New Orleans, USA

    2014

    X-ray Microscopy - Melbourne

    North American Cystic Fibrosis Conference - Atlanta, USA

    International Society of Aerosol Medicine - Sydney

    Australian Society for Medical Research - Adelaide

    American Society of Gene and Cell Therapy Conference - Washington, USA

      2013

      Australian Cystic Fibrosis Conference - Auckland, NZ

      Thoracic Society of Australia and New Zealand Conference - Darwin

      Stem Cells and Cell Therapies in Lung Biology Conference - Vermont, USA

      British Society of Gene and Cell Therapy Conference - London, UK

      2012

      North American Cystic Fibrosis Conference - Orlando, USA

      American Society of Gene and Cell Therapy Conference - Philadelphia, USA

      Thoracic Society of Australia and New Zealand Conference - Canberra

      2011

      North American Cystic Fibrosis Conference - Anaheim, USA

      Australian Cystic Fibrosis Conference - Melbourne

      Australian and New Zealand Society of Respiratory Scientists Meeting - Perth

      Thoracic Society of Australia and New Zealand Conference - Perth

      American Society of Gene and Cell Therapy Conference - Seattle, USA

      2010

      North American Cystic Fibrosis Conference - Baltimore, USA

      European Cystic Fibrosis Conference - Valencia, Spain

      Thoracic Society of Australia and New Zealand Conference - Brisbane

      Australian Health and Medical Research Conference - Melbourne

      • Cmielewski et. al., Long term gene expression with reporter and therapeutic lentiviral gene vectors in cystic fibrosis mice

      Australian and New Zealand Society of Respiratory Scientists Meeting - Brisbane

      American Society of Gene and Cell Therapy Conference - Washington, USA

      2009

      North American Cystic Fibrosis Conference - Minneapolis, USA

      Australian Cystic Fibrosis Conference - Brisbane

      American Society of Gene Therapy Conference - San Diego, USA

      Thoracic Society of Australia and New Zealand Conference - Darwin

    • News

      Cystic fibrosis news

      03

      Aug

      Stem cell research for cystic fibrosis leaps forward

      The fight against cystic fibrosis (CF) has taken a major step forward, with pioneering research by University of Adelaide scientists showing that cells causing the debilitating genetic disorder could be successfully replaced with healthy ones.

      more...