Martin Donnelley

Associate Professor Martin Donnelley

Associate Professor

Adelaide Medical School

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

I am an Associate Professor at the University of Adelaide, Leader of the Respiratory X-ray Imaging Laboratory (ReXIL), Co-Director of the Cystic Fibrosis Airway Research Group (CFARG) at the Women’s and Children’s Hospital in Adelaide, and a Robinson Research Institute Research Leader.

I completed my PhD in Medical Image Processing at the Flinders University of South Australia in 2008, and have spent the last ten+ years developing world-leading gene therapy methodologies, as well as technologies for the measurement of in vivo dynamic function in animal models. I am therefore in the unique position of having split the focus of my career equally on the fields of X-ray imaging and cystic fibrosis (CF) gene therapy, with the goal of using my advances in imaging to substantially improve outcomes in CF.

As the ReXIL Leader I have directed a program of X-ray imaging work that has enabled the imaging of respiratory processes at scales that have not previously been possible in vivo. I have 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 I performed with collaborator Dr Kaye Morgan (Monash University), that show we can also measure changes in airway surface liquid (ASL) depth in live anaesthetised mouse airways. We have now combined these methods into a single powerful airway health assessment method. In 2016 my collaborators and I published the first demonstration of the use of X-ray Velocimetry (XV), an X-ray based pulmonary function testing for the quantification of lung disease heterogeneity in B-ENaC mice. This unique and world-leading 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. I now have industry collaborations with 4DMedical (Prof Andreas Fouras) who have commercialised this technology. This work has been funded by the NHMRC and MRFF.

In 2014 my CFARG team published key data to show that our airway conditioning and lentiviral gene vector system produces correction of the CFTR defect in CF mouse nasal airways for at least 12 months. This work was the first to show improved survival in the gene vector treated CF group, supporting the prediction that CF airway gene therapy can produce significant health benefits. In 2017 I championed the development of Adelaide-based CF rat models using CRISPR/Cas9 gene editing, to facilitate further development of my group's airway gene therapy. The phenotype characterisation of these models was published in 2020.

All of this work has built towards a world leading capacity to perform rapid, non-invasive, direct, quantitative measurement of the effects of CFTR gene therapy on airway health and lung function.

Dr Donnelley performing XV imaging studies in B-ENaC mice at Monash University

Respiratory X-ray Imaging Laboratory (ReXIL)

The ReXIL aims to develop rapid and accurate outcome measures for assessment of airway disease using X-ray imaging. We have access to the SPring-8 Synchrotron in Japan and the Australian Synchrotron in Melbourne, as well as local X-ray imaging facilities at the SAHMRI PIRL facility at Gilles Plains. This enables us to image at a range of scales from micro through to macro, using small and large animal models. Our Honours and HDR projects focus on algorithm development for mucociliary transit assessment, and for measuring local lung function. We also use our cystic fibrosis rat models for evaluation of therapies.

Cystic Fibrosis Airway Research Group (CFARG)

The CFARG goal is to develop an effective genetic therapy for prevention or treatment of Cystic Fibrosis airway disease. Our 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, and creating and testing new delivery methods. We have access to a range of animal models (including CF mice and rats, and large animals), and a dedicated state-of-the-art research laboratory in the Gilbert Building at the WCH. Our Honours and HDR projects can be tailored to focus on any aspect of this work, and may be related to gene therapy studies in CF rats, assessment of in vivo gene expression, stem cell analyses including FACS analyses, and LV vector production improvements.

Example projects include, but are not limited to:

Project 1

Title: Demonstrating the effectiveness of gene therapy for altering CF-related lung and airway health in CF rat lungs

Description: An effective gene-addition therapy for CF lung disease requires accurate compound delivery to the target location, high levels of transduction, and effective CFTR protein expression in the cells relevant to CF disease. The aim of this project is to determine whether CFTR gene-addition alters the course of lung disease in our CF rat models, visualise the location of the transduced cells, and quantify how much expression is produced. This will be achieved with the use of tools such as PCR, histology, immunohistochemistry, and nasal potential difference assessment, as well as gene vector production.

Co-supervisor(s): Dr Patricia Cmielewski

Projects available for: Honours and HDR

Location: Women’s and Children’s Hospital

Research project start: Semester 1 or 2

Special Requirements: None

 

Project 2

Title: Demonstrating scalability to a human-sized lung

Description: Human lungs are substantially larger than in small animal models. They are also differently developed and branched, and cell type distributions and proportions along the conducting airways where CF pathophysiology begins are different. The aim of this experiment is to test the upscaling of our vector production and delivery procedures, and to quantify the effectiveness of our gene-addition protocol. Reporter gene vectors will be dosed into separate lung lobes of sheep, to enable the likely benefit of CFTR gene-addition to be assessed in a human-sized lung. LV vector will be produced in the larger quantities needed using our bioreactor methods, and will be delivered using standard human bronchoscopy equipment. The outcomes of this project will be achieved with the use of tools such as bioreactor gene vector production, PCR, histology, and immunohistochemistry.

Co-supervisor(s): A/Prof David Parsons & Ms Ali McCarron

Projects available for: Honours and HDR

Location: Women’s and Children’s Hospital

Research project start: Semester 1 or 2

Special Requirements: Vaccinations for large animal work

 

Project 3

Title: Measurement of CF lung function and airway surface health

Description: The ability to rapidly and accurately measure the effects of genetic or pharmaceutical therapies on airway surface health and lung function are very important. We have developed X-ray imaging technologies to quantify treatment efficacy.

At the SPring-8 synchrotron in Japan we can measure changes in the mucociliary transit behaviour of deposited tracking particles. Previously the location of the MCT marker particles in each image were tracked manually which is time consuming and subjective. An automatic method for detecting and tracking the particle locations would not only reduce the time required for analysis, but preliminary results have also shown it can increase the accuracy of the MCT measurements. A potential avenue of research could be to model the dynamics of the MCT marker particles to better predict their movement, which could also lead to a greater understanding of the physiology of the MCT system on a microscopic

At the imaging and medical beamline (IMBL) at the Australian Synchrotron we can use a technology called X-ray velocimetry (XV) to measure flow in each airway as it changes with mucus blockage or clearance. These studies allow us to quantify the patchy nature of CF lung disease, and enable the targeted delivery of treatments to those regions.

These projects are designed to examine the effects of genetic or pharmaceutical treatments on lung health. Depending on the expertise, skills and interests of the applicant it could involve computer science techniques such as image processing algorithm development and image data analysis, or alternatively it could be based on gene vector production, animal handling and molecular assessments.

Co-supervisor(s): A/Prof David Parsons and Dr Mark Gardner (External)

Projects available for: Honours and HDR

Location: Women’s and Children’s Hospital

Research project start: Semester 1 or 2

Special Requirements: Some travel may be involved.

  • Appointments
    Date Position Institution name
    2023 - ongoing Associate Professor University of Adelaide
    2019 - ongoing Research Leader Robinson Research Institute
    2018 - ongoing Career Development Fellow Robinson Research Institute
    2018 - ongoing Senior Research Fellow University of Adelaide
    2016 - 2017 Affiliate Senior Lecturer University of Adelaide
    2007 - 2017 Senior Medical Scientist Women's and Children's Hospital

  • Awards and Achievements
    Date Type Title Institution Name Country Amount
    2018 Fellowship Robinson Research Institute Career Development Fellowship University of Adelaide Australia -
    2017 Award Translational Research Award Women's and Children's Health Network Service Excellence Awards Australia -
    2013 Fellowship MS McLeod Postdoctoral Research Fellowship Women's and Children's Hospital Australia -
    2009 Award Semi-finalist for Young Investigator Award Women's and Children's Hospital Australia -

  • Education
    Date Institution name Country Title
    2002 - 2007 Flinders University Australia PhD
    1997 - 2000 Flinders University Australia BSc
    1997 - 2001 Flinders University Australia BEng (Biomedical) with Honours (First Class)

  • Research Interests
    Biomedical Engineering Gene and Molecular Therapy Radiology and Organ Imaging Respiratory Diseases Cardiac, Respiratory and Vascular Health Child and Adolescent Health Innovative Therapeutics

As Leader of the Respiratory X-ray Imaging Laboratory and Co-Director of the CF Airway Research Group, I worked with A/Prof David Parsons to grow my team from 1 RA in 2007 to 5 Postdocs, 2 RA’s and 4 PhD students in 2019. David retains his SA Health clinical role, managing the Women's and Children's Hospital lung function lab. We have a successful partnership with me as the lead full-time researcher driving the research programme.

I have had success with Cat 1, small grant, and philanthropic funding over the last 10 years, with $2.6 M awarded in the last 2 years (2.5x the previous 2), demonstrating rapid growth in research status and success enabling substantial team growth. My large grants include:

2019 Australian Lung Health Initiative, MRFF Frontier Health and Medical Research Program Stage One Grant: “4D Functional Diagnosis: A New Frontier In Lung Health For Children”, $960,000

2019 N. Farrow, M. Donnelley, A. Jaffe, D. Parsons, S. Waters, Orphan Disease Center Pilot Grant: “Airway Cell Therapy for Cystic Fibrosis Nonsense Mutations”, $73,000

2019-22 D. Parsons, M. Donnelley, K. Morgan, R. Boucher, T. Kuchel, NHMRC Project Grant: “Translating cystic fibrosis gene-addition therapy for use in human lungs: Demonstrating efficacy, safety and scalability”, $861,345

2019 N. Rout-Pitt, N. Farrow, J. Delhove, D. Parsons, M. Donnelley, WCH Foundation Grant: “Cell plasticity of the airways: Understanding the stem cell niche to optimise gene therapy and stem cell targeting”, $75,000

2019 J. Delhove, M. Donnelley, N. Farrow, D. Parsons, WCH Foundation Grant: “Designing immune-stealth, antiphagocytic targeting vectors for cystic fibrosis lentiviral gene therapy”, $75,000

2019 N. Farrow, M. Donnelley, P. Cmielewski, J. Delhove, D. Parsons, Channel 7 Childrens Research Foundation Grant: “Can neonatal exposure improve the effectiveness of cystic fibrosis gene therapy re-dosing?”, $34,625

2018-19 D. Parsons, M. Donnelley, M. Kitchen, K. Morgan, G. Zosky, J. Breen, USA CF Foundation Grant: “Lentiviral CFTR gene-addition in CF rat lungs: Effect of PA infection, safety and efficacy”, $282,491

2018-19 M. Donnelley, D. Parsons, Gandel Philanthropy Major Grant (via the Cure 4 CF Foundation): “An Australian gene therapy designed to cure CF lung disease: pre-clinical development of an essential, game-changing new lung health measurement technique”, $166,000

2018 M. Donnelley, Robinson Research Institute Career Development Fellowship, $50,000

2018 M. Donnelley, N. Farrow, P. Cmielewski, A. McCarron, D. Parsons, WCH Foundation Grant: “Effective re-dosing protocols for lasting cystic fibrosis lentiviral airway gene therapy”, $75,000

2017–18 D. Parsons, M. Donnelley, Fay Fuller Discovery Project Grant (via the Cure 4 CF Foundation): “Can in vivo delivery of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene soon after birth prevent the establishment and / or progression of Cystic Fibrosis (CF) lung disease?”, $670,292

2017 N. Farrow, M. Donnelley, P. Cmielewski, D. Parsons, WCH Foundation Grant: “Quantifying lentiviral mediated gene expression for cystic fibrosis lung disease in normal rat lungs”, $72,975

2017 C. McIntyre, D. Parsons, M. Donnelley, P. Cmielewski, Channel 7 Childrens Research Foundation Grant: “Gene therapy for cystic fibrosis”, $34,412

2017 M. Donnelley, C. McIntyre, N. Rout-Pitt, A. McCarron, D. Parsons, Channel 7 Childrens Research Foundation Grant: “Improving the efficiency of cystic fibrosis airway gene therapy”, $74,213

2016–18 D. Parsons, I. Bertoncello, M. Donnelley, R.Boucher, T. Kuchel, NHMRC Project Grant 1098127: “Identifying the role of airway stem cells in maintaining lentiviral mediated gene expression for cystic fibrosis lung disease”, $814,272

2015 M.Donnelley, K. Morgan, D. Parsons, A. Fouras, I. Lee, WCH Foundation Grant: “Next generation non-invasive airway surface health assessment: Combined surface hydration and mucus clearance analysis for CF treatment development”, $67,824

2015–17 D. Parsons, A. Fouras, J. Li, K. Siu, R. Boucher, K. Morgan, M. Donnelley, M. Kitchen, NHMRC Project Grant 1079712: “Revolutionising the diagnosis and monitoring of CF lung disease”, $792,778

2014 M.Donnelley, D. Parsons, A. Juhasz, E. Smith, K. Morgan, K. Siu, WCH Foundation Grant: “Lead air-pollution in children: Airway surface behaviour of inhaled particles and influence on blood levels”, $69,687

2013–16 M. Donnelley, MS McLeod Postdoctoral Fellowship: “Uptake of inhaled lead: Description and modelling of deposition, and determinants of vascular uptake”, $310,000

2012 M.Donnelley, D. Parsons, K. Siu, A. Fouras, K. Morgan, WCH Foundation Grant: “Understanding the clearance of inhaled lead dust in the conducting airways using synchrotron imaging”, $43,754

2011 D. Parsons, A. Fouras, K. Siu, S. Hooper, M. Donnelley, Australian Cystic Fibrosis Research Trust Grant: “Localised detection of early stage CF disease via quantitative imaging of lung motion”, $110,749

2010–12 D. Parsons, K. Siu, M. Donnelley, W. Skinner, NHMRC Project Grant 626863: “Synchrotron X-ray assessment of airway surface physiology for cystic fibrosis”, $765,702 (Score of 7)

2009 D. Parsons, M.Donnelley, K. Siu, N. Yagi, M. Kitchen, WCH Foundation Grant: “Dynamic synchrotron x-ray detection of individual pollutant particle behaviour after deposition onto live airways”, $54,360

I am passionate about ensuring students and ECR’s get the best start to their research career. I co-coordinate the Robinson Research Institute (RRI) mentoring program.

In my team I drive targeted EMCR career mentoring, providing regular encouragement, support, and direction that is often overlooked, particularly in the current uncertain medical research funding environment. I connect them to leading groups, providing travel to labs at: JASRI (Japan); UNC, UPenn and Cedars-Sinai (USA); Imperial College (UK); Monash and the IMBL.

As a primary/secondary supervisor, I encourage active student involvement in grant and paper writing, and submission processes, with one student (A McCarron) listed as a CI on two recent grants, as well receiving the 2019 CFA Anne Maree Bosch ECF. I encourage my students to be involved in the 3 min thesis competition; one (H Padmanabhan) represented UofA at the national level. Four of my Honours students have published their work and gone on to PhD’s, and 1 is now an MD (J Penny-Dimri) continuing to publish in CF.

  • Current Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2023 Co-Supervisor Paediatric Regional Lung Function Assessment Via X-Ray Velocimetry In Children With Cystic Fibrosis Doctor of Philosophy Doctorate Full Time Mr Matthew Russell Bruorton
    2023 Principal Supervisor Understanding and improving gene vector targeting with lentiviral magnetic nanoparticles Doctor of Philosophy under a Jointly-awarded Degree Agreement with Doctorate Part Time Ms Madison Michelle Davis
    2021 Principal Supervisor Improving the effectiveness of airway lentiviral gene therapy for cystic fibrosis Doctor of Philosophy Doctorate Full Time Mrs Nikki Reyne

  • Past Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2016 - 2021 Co-Supervisor Overcoming Challenges to Development of a Lentiviral-Mediated Airway Gene-Addition Therapy for Cystic Fibrosis Doctor of Philosophy Doctorate Full Time Miss Alexandra Sarah Ann Mc Carron
    2013 - 2019 Co-Supervisor Development of Lentiviral Airway Gene Therapy Aerosol Delivery Techniques for Cystic Fibrosis Doctor of Philosophy Doctorate Full Time Ms Harshavardini Padmanabhan
  • Position: Associate Professor
  • Phone: 81619181
  • Email: martin.donnelley@adelaide.edu.au
  • Fax: 81619192
  • Campus: Womens & Childrens Hospital
  • Building: WCH - Gilbert Building, floor G
  • Org Unit: Women's and Children's Health
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