Funded Research

CFRL Pathways to Treat Intractable Lung Infection in CF Lung Transplant Recipients Grant 2023 (sponsored by Cystic Fibrosis Research Limited)

Project Title:  New pathways to treat intractable lung infection in lung transplant recipients with cystic fibrosis

Name:  Amy Pham

Institution: University of Queensland

Value: $48,074

Duration: 1 year

Summary:  Lung transplantation is an invaluable medical procedure that is often the only hope for cystic fibrosis (CF) patients with end stage lung disease. Today in Australia, lung transplantation saves and breathes new life into more than 160 patients a year. However, despite significant advances over recent decades median survival remains unacceptably low at around 5 years. Microbial infection, particularly by Pseudomonas aeruginosa, is one of the key drivers associated with lung dysfunction and rejection post transplantation. Infection is difficult to manage clinically as many are intrinsically resistant to many antibiotics. Our research has identified a specific type of antibody that instead of protecting against infection, actually cloaks and protects the bacteria from immune killing. Termed ‘cloaking antibodies’ when removed restore killing of the bacteria without the need for antibiotics. This research aims to expand the relevance of cloaking antibodies to other common lung pathogens, including Burkholderia spp. which often means lung transplantation is not an option in CF patients. 

Reports: None due 

CFWA Post Graduate Top Up Scholarship 2023 (sponsored by Cystic Fibrosis Western Australia)

Project Title:  Assessing aerosolised bacteriophage to treat antibiotic resistant bacterial infections

Name:  Rohan Flint

Institution:  University of Australia/Telethon Kids Institute

Value: $37,500

Duration: 3 years

Summary:  P. aeruginosa is a prominent respiratory pathogen that is becoming resistant to an increasing number of antibiotics. With antimicrobial resistance (AMR) emerging in many bacterial pathogens at an alarming rate and the number of effective anti-microbial drugs diminishing, novel treatment methods are urgently needed. Phage therapy remains a promising alternative and adjunct to current antibiotics. One aspect to consider for phage therapy is the delivery method, which will vary depending on where infection occurs. Nebulisation and inhalation of bacteriophage remains the preferred approach for AMR respiratory infections, as this enables the delivery of phage(s) directly to areas of bacterial colonisation. However, little is known of the effects of aerosolisation on the stability and function of phages, and this is further complicated by the fact that phage stability varies across individual species. This project will hence assess the effects of aerosolisation on phage viability and resulting activity. Furthermore, identified phage(s) that remain infective after aerosolisation, will then be used to create phage suspensions for preclinical inhaled delivery assessment. Using human cells, we will establish a 3-dimensional model of the airway. We will then establish P. aeruginosa infections and assess the effects of aerosolised phage delivery on bacteria as well as host airway responses

Reports: First Report

Conquer Cystic Fibrosis Lung Health Transplant Grant 2022

Project Title:  Transforming diagnosis of lung transplant rejection

Name:  Herbert Ludewick

Institution: Health and Lung Research Institute, WA

Value: $50,000

Duration: 1 year

Summary:  Lung transplant is a transformative therapy for those patients with end stage CF lung disease. Despite this, half of all lung transplant recipients will die within 6-7 years mainly due to the cumulative effects of the patient’s body rejecting the donor lungs in spite of powerful medications to suppress this normal immune response. Accurate diagnosis of lung rejection episodes and timely treatment can lengthen healthy survival for CF patients receiving lung transplantation.  At present screening for and diagnosing rejection requires regular sampling of the lungs themselves requiring general anaesthesia and the risk of lung collapse and serious bleeding.   It is known that during rejection, more lung DNA is released into the blood. Our project aims to find a signature specific to DNA from the lung and test for it in the blood. In this way a blood test will be able to more accurately and simply, diagnose lung rejection, eliminating the need for, and risks of, regular lung biopsy in transplant recipients.  We believe that transforming the diagnosis of lung rejection in this way, will significantly improve the quantity and quality of CF patients who have undergone lung transplantation.  

Reports:  None due

Cystic Fibrosis Research Limited (CFRL) Innovation Grant 2022

Project Title: Improving detection and assessment of lung disease in young children with cystic fibrosis

Name: Tamara Blake

Institution: University of Queensland

Value:  $80,000

Duration: 1 year

Summary:  In Australia, one in 2,500 babies are born with cystic fibrosis (CF). lrreversible damage to their lungs begins very early in life and often without any symptoms. A significant limitation to early disease detection in patients with CF has been the lack of safe and sensitive measures suitable for use in infants and toddlers. Currently, the only methods available to monitor lung changes is performed under sedation in specialised laboratories. This is often a traumatic experience for patients and their families. We propose to assess the appropriateness of a new, innovative technique that can easily and reliably measure lung function in very young children. Oscillometry can be performed during quiet sleep and is very sensitive to early changes in the CF lung. Results from this pilot study will inform future study designs that will aim to better understand the mechanisms of early CF lung disease and better define the role of new sensitive measures that can monitor disease progression. Use of this technique in this population will also provide parents and physicians with detailed lung health information much sooner than current methods.

Reports: None due
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Abbie Fennessy Memorial Fellowship 2022 (sponsored by Mediplast)

Project Title: Investigations into the associations between exercise, physical activity and sedentary behaviour with glycaemic control in adults with cystic fibrosis after initiation of Trikafta TM.

Name: Tiffany Dwyer

Institution: University of Sydney

Value:  $5,000

Duration: 1 year

Summary:  The aim of the grant is to perform continuous glucose monitoring (CGM) during supervised moderate intensity exercise and unsupervised habitual physical activity, to determine the prevalence of hypoglycaemia and glucose variability in adults with CF after they are established on TrikaftaTM. Comparisons will be made between participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and CFRD. 

Reports: None due
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Cystic Fibrosis Lung Health Grant 2022

Project Title: Does the MetaNeb®, a new airway clearance device, change measure of lung oxygenation, secretion clearance and other measure of lung function in adults with CF when they are well?

Name: Naomi Chapman

Institution: Curtin University, WA

Value:  $5,000

Duration: 1 year

Summary:  The aim of this study is to determine whether in adults with stable CF, a single treatment session using the MetaNeb® produces greater change in measures of secretion clearance and lung oxygenation using fMRI and other measures of lung function compared to normal huff and cough.  We hypothesise that the treatment session that includes the use of the MetaNeb® device will produce greater changes in these measures, when compared with the treatment session that comprises huff and cough alone. 

Reports: None due
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The Dorothy Nell Marzol Innovation Grant 2022

Project Title: Australian-wide surveillance for fungal infection: A national metagenomic analysis across 19 CF centres

Name: Steven Taylor

Institution: South Australian Health & Medical Research Institute

Value:  $80,000

Duration: 1 year

Summary:  Lung infections associated with cystic fibrosis (CF) are devastating. They contribute to both everyday breathlessness as well as the acute lung events. The microbes that cause these lung infections are under constant pressure to adapt and change to the treatments that doctors prescribe to try and eradicate them. Over the last few years, several revolutionary changes have been made to how people with CF are treated. We are already seeing that the main bacteria associated with CF lung infections are declining because of these therapies. However, previously when we see changes to the microbes that cause lung infections, we see emergence of new microbes. This poses great risks as treatment plans for these new microbes are less established. My research will investigate the lung “microbiome” of over 900 samples already collected from people with CF across Australia. This will include looking at the fungi in the lungs, which are often overlooked, but which are known to become more common following changes to treatment. By looking at samples collected before and after starting new treatments, we can identify key microbes to monitor, giving us the best chance to protect people with CF from new infections. 

Reports: 6 month progress report>
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ACFRT Top Up Scholarship 2021

Project Title: The impact of helpful and harmful immune responses in the CF lung

Name: Emma Ledger

Institution: University of Queensland Diamantina Institute

Value:  $15,000

Duration: 3 years

Summary:  Pseudomonas aeruginosa is a highly multi-drug resistant bacteria which causes chronic lung infections in individuals with cystic fibrosis (CF). This bacterium is extremely difficult to eradicate and is a major cause of morbidity and mortality in CF. Our research investigates specific antibodies produced by patients that enhance, rather than clear these bacterial infections resulting in further disease burden.  This project aims to better understand the prevalence, impact, and mechanisms of these ‘bad antibodies’ in individuals with CF by characterising them for the first time within patient sputum and towards the patient’s infecting strain. Additionally, we aim to investigate the impact the latest CF transmembrane conductance regulator (CFTR) modulator therapies have on P. aeruginosa infection and these dysregulated antibody responses. This research is critical for the development of targeted therapies to neutralise these ‘bad antibodies’, clear persistent multi-drug resistant lung infections and improve patient outcomes further in this post-modulator era. 

Reports: Six month progress report
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CFWA Golf Classic Grant 2021 (sponsored by CFWA)

Project Title: Neutrophils in CF

Name: Luke Garratt

Institution: Telethon Kids Institute/University of Western Australia

Value:  $28,000

Duration: 1 year

Summary:  In cystic fibrosis (CF), neutrophils accumulate in areas of the lung as mucus builds up and germs infect the airways. My research has found that in CF airway inflammation, neutrophils choose to actively release their harmful products rather than trying to eat and kill the germs causing infection. In a laboratory model of CF airway inflammation, we have found that only certain germs induce this behaviour. We are now studying how the gene expression of neutrophils determines their function, with the aim to understand whether we can prevent certain functions by inducing or repressing genes within the neutrophil. This CFWA funded project is exploring the ability of new nanoparticle technologies to modify gene expression in neutrophils, as neutrophils are short-lived cells that do not respond to traditional methods. The hope is that this technology could inform a new class of anti-inflammatories for controlling neutrophil behaviour in CF airways.

Reports: Interim Report
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The Cystic Fibrosis Metabolic Monitoring Grant 2021

(sponsored by COSMED Asia-Pacific Pty Ltd)

Project Title: The road map to personalised diet management in children with cystic fibrosis

Name: Hiran Selvadurai and Andrea Kench

Institution: The Children's Hospital, Westmead

Value:  $5,000

Duration: 1 year

Summary:  We  know that people with cystic fibrosis (CF) need more energy from food to grow and fight infections than healthy people. However, there is very little information available on specific macronutrient (carbohydrate, protein and fat) requirements for children with CF. In particular, it is not known how macronutrients contribute towards fueling the body during periods of rest and during exercise. This information is needed so that we can implement personalised nutritional goals. This is particularly important in the context of new CF treatments (modulator medications) which have led to a significant improvement in lung function, weight and quality of life. Further, significant infections such as NTM is a growing problem in patients with CF but it is not clear how these infections impact on macronutrient use and energy expenditure in children with CF. Exciting new technologies now enable us to quantify nutritional macronutrient requirements for children. The purpose of this research study is to ascertain if we can determine macronutrient requirements for children with CF.  

Reports: 6 month progress report
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Ann Maree Bosch Career Fellowship 2021

Project Title: Progressing novel treatment options to improve management of infections in people with cystic fibrosis

Name: Stefanie Bader

Institution: Walter & Eliza Hall Institute of Medical Research

Value:  $10,000

Duration: 1 year

Summary: Bacterial infection is the most common cause of death in people with cystic fibrosis (CF). The immune cells responsible for combating bacteria are often defective in CF patients and can damage the lungs and gut while trying to fight infection. This reaction worsens disease and fails to kill the pathogen. We propose to use a new class of drugs that can tackle this problem in two ways: by killing infected host cells, reducing the number of bacteria and by removing defective immune cells. This approach has the potential to improve quality and length of life in people with CF by addressing disease in the lung and the gut.  The Fellowship would provide an invaluable opportunity for me to travel to a lab in the Netherlands which specialises in CF and the gut. There, I would be able to test our drugs both in in-vivo and organoid models of CF gut disease to gain substantial knowledge on how to apply their techniques to our research at WEHI. This would allow my lab to test a greater array of drugs in Australia. I will share the techniques I learn, not just with my lab at WEHI, but with other CF researchers in Australia. 

Reports: Six month report and Final Report

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Conquer CF (Respiratory) Innovation Grant 2021

Project Title: Establishing a pipeline for repurposing anti-inflammatory drugs to tackle viral-induced exacerbations in children with cystic fibrois.

Name: Samuel Montgomery

Institution: Curtin University/Telethon Kids Institute

Value:  $50,000

Duration: 1 year

Summary:  This study aims to improve the lung health of young children with cystic fibrosis (CF) following a viral infection. Rhinovirus infection (the “cold” virus) is common in young children, often resulting in presentation to hospital emergency departments. This is worsened in children with chronic airway disease such as the inheritable disease cystic fibrosis (CF) where infection with rhinovirus results in deteriorating lung health, sadly often permanently, leading to chronic bacterial infection and increased hospitalisation. Rhinovirus infects the cells lining the airway (the “epithelium”) provoking a large inflammatory response, which can lead to lung damage. We have previously identified a specific type of inflammation which is associated with decreasing lung health in children without bacterial infection. We propose to block this inflammation using a drug, interleukin-1 receptor antagonist, as a new anti-inflammatory treatment for the cold virus in children with CF. We will use a model of the airway in the laboratory to test the safety and effectiveness of this drug to reduce this inflammation. This study aims to provide evidence to progress to a clinical trial, as this drug is already approved for use in other diseases and could be rapidly translated into clinical use for children with CF. 

Reports: None due
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CFWA Golf Committee Contribution to CF Research 2021

Project Title: Does a diagnosis of Tracheobronchomalacia affect health outcomes in children with cystic fibrosis?

Name: Julie Depiazzi and Crystal Bourke

Institution: Perth Children's Hospital

Value:  $5,000

Duration: 1 year

Summary:  Around 41% of young children with cystic fibrosis (CF) in Western Australia have been reported to have tracheobronchomalacia (TBM) seen during bronchoscopy – a condition where parts of the windpipe or airways are floppier than would be considered normal. In the short-term this TBM finding can lead to a change of the child’s daily physiotherapy and airway clearance program, however despite its prevalence, little is known about the long-term impact of TBM. 

The aim of this study is to compare health outcomes of children with CF, both with and without TBM, up to the age of 4 years, and will include imaging, inflammation markers and infection comparisons. We hope our findings will provide clinicians and families with more insight into, if any, long-term impacts of this condition.

Reports: None due
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Conquer CF (GI) Innovation Grant 2021 

Project Title: Short Chain Fatty Acids and Gastrointestinal complications in cystic fibrosis

Name: Josie van Dorst

Institution: University of New South Wales

Value:  $50,000

Duration: 1 year

Summary: Cystic fibrosis (CF) is a life-shortening genetic condition, which causes thick mucus, chronic infection, and inflammation not only in the lungs but also the gut. People with CF also have an imbalance between beneficial and harmful gut bacteria, which are linked to poor growth, gut symptoms, chronic gut inflammation and increased cancer risk. Short chain fatty acids (SCFA) are produced by beneficial bacteria in the gut, mainly from prebiotic dietary fibres. SCFAs fuel the activities of beneficial bacteria and have many important roles in the gut and wider health, including combating inflammation and cancer activity, and regulating the communication with the lungs (gut-lung axis) and the immune system. Despite this, there is limited knowledge regarding SCFA in individuals with CF.

Reports: None due
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Abbie Fennessy Memorial Fellowship 2021 (sponsored by Mediplast)

Project Title: The Early Childhood Project: Circle of Security-Parenting in cystic fibrosis (CF)

Name: Stella Li

Institution: The Children's Hospital, Westmead

Value: $5,000

Duration: 1 year

Summary:  This project focuses on supporting parents of children with CF during the early childhood period (under 5). This is a period that often coincides with CF diagnosis and can be filled with stress, worry, and guilt. We are offering the Circle of Security parenting program which aims to help parents reflect on and meet their child's medical and emotional needs and ultimately strengthening the parent-child relationship.

Reports:  none due
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CFWA Top Up Scholarship 2021

Project Title: Studying how pseudomonias aeruginosa becomes resistant to phage therapy to identify how to prevent it occuring

Name: Andrew Vaitekenas

Institution: Curtin University

Value:  $37,500

Duration: 3 years

Summary:   Psuedomonas aeruginosa causes harmful lung infections in CF lungs and becomes resistant to existing antibiotic treatments. There is a lack of antibiotics being developed and alternative treatments are needed. A therapy using viruses that specifically kill bacteria is effective, but P. aeruginosa can become resistant to this too. My project aims to understand how P. aeruginosa becomes resistant to phages and what this means for the bacteria. I will use this knowledge to develop and test strategies that increase the effectiveness of phage therapy and prevent resistance occurring. These strategies can aid our group in making phage therapy a regularly used therapy, preventing further resistance and treating those with infections that are currently untreatable.

Reports: None due
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Special CF Research Seeding Grant 2021 (sponsored by CFACT)

Project Title: Development of new mucus-thinning drugs for CF patients

Name: Shiyi Xi

Institution: The Walter & Eliza Hall Institute of Medical Research

Value:  $5,000

Duration: 1 year

Summary:   Mucus-based airway obstructions and the complications they cause are a significant source of morbidity and mortality in CF patients. The current leading mucolytic drug Pulmozyme® only works on 70% of patients, and many people would greatly benefit from more effective alternatives. This project will focus on a promising new target for novel mucolytic drugs - a mucus-thickening protein called trefoil factor-3 (TFF3). My lab has generated and identified 15 candidate antibodies that antagonize TFF3 activity and will be evaluated on patient sputum samples. We aim to benchmark the activity of these potential mucolytics against Pulmozyme® and to assess if they have additive of synergistic activities with the current drugs.

Reports: Six month report, Final report

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ACFRT Studentship Grant 2021 (sponsored by CFRL)

Project Title: Investigation of factors influencing glucose control in cystic fibrosis 

Name: Rebecca Keating

Institution: University of Queensland

Value:  $15,000

Duration: 3 years

Summary:   This research project will aim to determine whether the use of DPP4 inhibitors assist in removing blood glucose levels for the entire day in individuals with CF impaired glucose tolerance. It will assess its effects on gut hormoneas, gut microbacteria and inflammation. It will also determine whether using a mixed meal tolerance test may be more useful in determining CF impaired glucose tolerance.

Reports: None due
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Lung Health Grant 2021 (sponsored by FBM)

Project Title: Telehealth to promote mucociliiary clearance in adolescents with cystic fibrosis

Name: Anna Middleton

Institution: The Children's Hospital, Westmead NSW

Value:  $5,000

Duration: 1 year

Summary:   CF adolescents with poor adherence to airway-clearance and exercise will be randomised to a 4-week block of either stationary airway-clearance or the same routine interspersed with short intervals of exercise. Sessions will be supervised by a physiotherapist over telehealth twice a week. After a 2-week wash-out period participants will cross-over to the alternative intervention. Adherence, ease of expectoration, spirometry and exercise perceptions will be measured after each block of therapy. We hope to evaluate whether telehealth in CF adolescents improves airway-clearance technique and adherence and whether the addition of short intervals of exercise interspersed during airway-clearance improves mucociliary-clearance.

Reports: None due
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Innovation Grant 2021 

Project Title: Safety and effectiveness of triple-caftor combinations in cystic fibrosis during pregnancy

Name: Elena Schneider-Futschik

Institution: University of Melbourne

Value:  $80,000

Duration: 1 year

Summary:   The recent approval of the novel CFTR modulator triple combination Trikafta targets the majority of cystic fibrosis (CF) patients, but potentially excludes pregnant women as the clinical efficacy of these important drugs is limited by our lack of understanding what short and long-term effects these drugs could have on developing babies. This project will investigate the entry of the triple combination across the placenta in an animal CF model that replicates a common CF mutation. The project will also assess the potential of maternal administration of these drugs to reduce the amount of CF damage occurring before birth. This innovative approach has significant potential in improving clinical practice worldwide

Reports: None due
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Innovation Grant 2021 (sponsored by CFSA) 

Project Title: Sphingosine-1 phosphate and zinc - novel mediators of vascular dysfunction in children with CF

Name: Andrew Tai

Institution: The University of Adelaide

Value:  $50,000

Duration: 1 year

Summary:   We continue to collect lung and blood samples from children with CF and controls. There was a delay with bronchoscopy procedures for a few months during the recent COVID surge. Samples will be tested in parallel when sufficient numbers are obtained. We have optimised all techniques, completed testing of markers of vascular dysfunction in blood from adult CF patients (as comparators for the paediatric bloods), and are undertaking mechanistic in vitro studies focusing on changes in the sphingosine signalling pathway and markers of endothelial functions in cell lines. Significant changes to date have included an activation of the ET-1/TGFb/pSmad axis in adult CF patients; data that will advise our investigations using the paediatric CF samples. In a mechanistic approach the effects of the CFTR inhibitor CFTRinh172, and CFTR correctors (Ivacaftor and Elexacaftor) are used for testing whether these changes are caused intrinsically by CFTR impairment in the patients cells.  

Reports:   None due

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Conquer CF (Respiratory) Innovation Grant 2020

Project Title: Designing optimal phage cocktails for kids with cystic fibrosis (DOCK-CF)

Name: Ameneh Khatami

Institution: University of Sydney

Value:  $50,000

Duration: 1 year

Summary:   To manage chest infections, children with cystic fibrosis (CF) are exposed to broad-spectrum, toxic antibiotics several times per year. This is only moderately effective, with infections often becoming increasingly difficult to treat due to evolving antimicrobial resistance. Bacteriophages (phages) are viruses that replicate within bacteria, causing highly selective bacterial killing. Since phages do not attack human cells they are safe for clinical use, and their targeted bacterial killing reduces their impact on our healthy microbiome (commensal bacteria). Thus, phage therapy offers a safer and more precise solution than antibiotics.We hypothesise that Pseudomonas aeruginosa and Staphylococcus aureus strains that colonise children with CF can be eradicated effectively by combinations of phages (“phage cocktails”). This would result in reduced lung damage and allow recovery of normal lung growth, improving the life expectancy of children with CF. In addition, reduced toxicity and microbiome effects compared to antibiotics would improve quality of life for patients and their families. This proposal aims to identify phages with ‘killing’ activity against the main strains of these bacteria isolated from a large cohort of children with CF.  Research outcomes will feed into a translational pipeline to investigate this promising therapy in children with CF within 5 years.

Reports: Interim Report

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Golf PhD Top Up Scholarship 2020 (sponsored by CFWA)

Project Title: Me, myself and I: An exploratory study of self-concept in adults with Cystic Fibrosis (CF) in an evolving era of care.

Name: Maggie Harrigan

Institution: University of Western Australia

Value:  $37,500

Duration: 3  years

Summary:   The PhD study explores self-concept (sometimes called self-identity) e.g. how you view yourself, a sense of who you are as a person in the various aspects of life. Outside CF, self-concept has been widely associated with improved health, however there is currently a lack of self-concept research within CF. I will be examining levels of self-concept within the adult CF community and associations between self-concept, mental, social and physical health. The study will also explore the potential impact of evolving CFTR modulator treatments on self-concept.  As CF treatments evolve, what is means to have CF continues to change, potentially bringing new opportunities and challenges.  Amidst this change it is pertinent to develop our understanding of the social and emotional needs of those living with CF.  

Living with cystic fibrosis during the COVID-19 pandemic: a social connectedness perspective

Reports:  none due

Golf PhD Top Up Scholarship 2020 (sponsored by CFWA)

Project Title: Investigating an alternative therapeutic agent for the treatment for bacterial infections in kids with cystic fibrosis

Name: Joshua Iszatt

Institution: Curtin University

Value:  $37,500

Duration: 3  years

Summary:   This project is focused around the development and investigation of a therapeutic agent that could be used to treat multi-drug resistant bacteria that frequently cause persistent lung infections in children with cystic fibrosis.

Reports:  Progress report

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Ann Maree Bosch Fellowship 2020

Project Title: The Gut-Lung Axis in early cystic fibrosis (GLAX-CF)

Name: Katherine Frayman

Institution: Murdoch Children's Research Institute

Value:  $9,500

Duration: 1 year

Summary:  My research explores the development of the gastrointestinal and lower airway microbiota during the first two years of life in newly diagnosed infants with cystic fibrosis, and their relationship to each other, to lower airway inflammation and to clinical manifestations of disease. It will examine the impact of continuous antibiotic prophylaxis on the microbial milieu in both niches, and its relationship to clinically relevant outcomes. Ultimately, my research aims to highlight opportunities for intervention, for example, modification of the gastrointestinal microbiota with pro-, pre- or antibiotics, in order to influence respiratory phenotype. The Ann Maree Bosch Career Fellowship will enable me to travel to the United States to establish key collaborations with the University of Washington and Seattle Children’s Hospital, Washington and attend the North American Cystic Fibrosis Conference.

Reports:  None due 

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Conquer CF (GI) Innovation Grant 2020

Project Title: Towards understanding gut host-microbe interactions and personalised probiotic therapy in cystic fibrosis using organoid-derived 2D intestinal models

Name: Keith Ooi

Institution: University of New South Wales

Value:  $50,000

Duration: 1 year

Summary: Cystic fibrosis (CF) is a life-shortening genetic condition, which causes thick mucus, chronic infection, and inflammation in the lungs and gastrointestinal (GI) tract. People with CF have an imbalance in their GI bacterial population (microbiome) known as “dysbiosis”, and chronic GI inflammation, both of which are linked to poor growth, GI symptoms and increased cancer risk. A survey of CF patients and clinicians globally has ranked GI symptoms 2nd in priority, ahead of respiratory issues, yet no GI-specific therapies currently exist. Stem cells obtained from gut biopsies from people with CF can be used to grow 2-dimensional and 3-dimensional organoid culture systems which replicate real life (“mini guts”). We will investigate the host-microbe interactions involved in GI dysbiosis, inflammation and malignancy, using CF patient-specific intestinal organoids. We believe this study will provide a crucial step towards personalised therapies based on host-microbe interactions with the aim of reducing GI complications in CF. Successful personalised therapies would revolutionise CF treatments and other conditions subject to host-microbe interactions. 

Reports: 6 month report

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Abbie Fennessy Memorial Fellowship 2020

 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia)

Project Title: CF Physio.com:  development of interactive and education videos of inhalation therapy and airway clearance

Name: Jen Hauser & Jenny Bishop

Institution: Royal Hobart Hospital & Westmead Hospital

Value: $5,000

Duration: 1 year

Summary:  CFPhysio.com is an educational website which currently translates the TSANZ clinical practice guidelines “Physiotherapy for CF”, and evidence based educational literature into a practical, self-paced, educational resource for physiotherapists. The website currently provides a platform for education and learning of evidence-based physiotherapy management in cystic fibrosis, for physiotherapists. Since its official launch in August 2019, over 400 physiotherapists have registered and used the site. A second stage of the project is proposed, including the provision of educational resources for individuals with CF, carers, family, friends, employers, teachers etc, including video content of inhalation therapy and physiotherapy treatment techniques. 

Reports:  Final Report

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Innovation Grant 2020

Project Title: Enhancing the innate ability of CF macrophages to kill and clear MABS

Name: Abdullah Tarique

Institution: University of Queensland

Value: $80,000

Duration: 1 Year

Summary: Currently 13-20% of patients with CF are infected with Mycobacterium abscessus (MABS) and there is growing concern that increasing incidence of MABS infection is leading to accelerated pulmonary decline, and to reduced survival. MABS are notoriously difficult to treat, in part because of widespread antibiotic resistance, thus necessitating the use of toxic drug regimens. We herein propose to evaluate an alternative approach to clear MABS by boosting the anti-bacterial responses of CF patients using novel therapeutic agents. Macrophages are the professional killer cells that kill bacteria including MABS from the lungs. Sputum and venous blood are the two main sources for macrophage researchers. Due to inadequate volume of patient’s specimen available for research, macrophage researchers struggle in getting enough macrophages from patients’ specimen which thereby limit macrophage research in CF. We herein propose to develop an immortalized CF macrophage cell line that will offer indefinite supply of CF macrophages to the researchers to investigate macrophage defect in CF as well as finding out ways to improve their anti-microbial responses in CF.

Reports: Final Report

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Ann Maree Bosch Career Fellowship 2019

Project Title: Targeting a forgotten cell to prevent cystic fibrosis lung disease

Name: Shivanthan Shanthikumar 

Institution: Murdoch Children's Research Institute

Value: $9,000

Duration: 1 year

Summary:  The life expectancy for someone born with cystic fibrosis (CF) today is only 44 years. In CF the major cause of shortened life expectancy, as well as reduced quality of life, is lung disease. A major cause of lung disease in CF is excessive inflammation which causes to irreversible lung damage. Currently a number of treatments are used in CF such as antibiotics and chest physiotherapy, however no treatments target inflammation. There are new treatments which address the malfunctioning ion channel which causes CF, however these treatments only target specific certain genetic mutations, and so not all patients benefit from them. Any treatments aimed at inflammation in CF would benefit all patients, and could be used together with existing and new treatments. There are a number of different cell types that contribute to inflammation, however one that has not been investigated is the alveolar macrophage. These cells only exist in the lung and are one of the initial cells that trigger an inflammatory response. There are multiple types of alveolar macrophages in CF lungs, and thus far they have not been studied. The overall aim of my research is to identify targets for treatment relating to alveolar macrophages.

Reports: Final Report

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Innovation Grant 2019 CFCC Victoria

Project Title: Colorectal Cancer

Name: Keith Ooi

Institution: University of New South Wales

Value: $50,000

Duration: 1 Year

Summary: Adults with cystic fibrosis (CF) now face new complications such as colorectal cancer (CRC). The cause is unknown but gut inflammation and gut bacteria imbalances are possible causes. The risk for CRC in CF is high enough that new CRC screening guidelines recommend colonoscopy for patients >40 years and for post-transplant patients >30 years old. Performing colonoscopies in adult CF patients is complex due to comorbid diseases including poor lung function and diabetes. Non-invasive screening tests are needed, similar to faecal occult blood testing (FOBT) used for general population screening. While FOBT utility in CF remains unclear, other stool tests for gut inflammation (calprotectin and M2-PK) have shown promise in detection of CRC and polyps in the general population. They are elevated in children with CF and may be potential early markers of future CRC in adults with CF. To investigate this further, we will invite patients who meet criteria for CRC screening to provide stool samples prior to their scheduled colonoscopies. Markers of gut inflammation including calprotectin and M2-PK, FOBT and imbalances in gut bacteria will be assessed and compared with incidence of CRC and number of adenomas. Predictors for colorectal cancer and precancerous lesions will also be assessed.

Reports: 6 month report

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CFWA Golf Classic Scholarship - WA Top Up Grant 2019

Project Title: Exploring the therapeutic potential of phage therapy to treat Pseudomonas aeruginosa infection in people with cystic fibrosis

Name: Renee Ng

Institution: University of Western Australia

Value: $37,500 

Duration: 3 years

Summary: This study aims to explore a new treatment option for patients with bacterial lung infections using bacteriophages (‘phages’), a virus that targets and “eats” bacteria, eradicating them. Phage therapy is cheaper causes no side effects which is seen with currently used antibiotics. This project aims to understand if phage therapy can kill the bacteria and reduce the inflammation caused by infection.

Reports:  Final Report

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CFWA Golf Classic Scholarship - WA Top Up Grant 2019

Project Title:  Does the MetaNeb®, a new airway clearance device, change lung function in adults with cystic fibrosis when they are well and when they are hospitalised for a lung infection?

Name: Naomi Chapman

Institution: Curtin University

Value:  $37,500

Duration: 3 years

Summary:  Cystic fibrosis (CF) is an inherited lung disease that causes excessive airway secretions, damaging airways and leading to chronic infection. Clearing the airways is a vital component of their care and is believed to reduce lung infections and slow disease progression. Although there are a range of techniques used to clear airway secretions, there is no evidence to support one over others. Therefore, the choice of technique is based largely on patient/therapist preference. This project will look at the effects of a new airway clearance device called the MetaNeb®, on lung function, secretion clearance and CF related symptoms in adults with CF who are well and those hospitalised with a respiratory exacerbation or chest infection. If this device is shown to be more effective than the commonly used techniques, this would be of great clinical significance as it will assist in guiding clinical use of the device throughout CF centres in Australia and internationally.

Reports:  None due

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