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Awarded $501,106

Bringing the benefits of precision medicine to children in Western Australia

Timo Lassmann, Jenefer Blackwell, Gareth Baynam, Alistair Forrest

Genome medicine, fuelled by ever decreasing sequencing costs, is rapidly making its way into the clinic.

National and international programs, prominently including the Global Alliance for Genomics and Health (GA4GH) and the Australian Genomics Health Alliance (AGHA) are accelerating the adoption of sequencing-based genetic tests and lead efforts in standardization and data sharing.

While genomics is also a key component in P4 medicine, allowing us to understand an individual's predisposition to disease, disease progression and response to treatment, P4 medicine has a much broader scope aiming at disease prevention and prominently involving consumers. Here we have assembled an array of innovative technologies (whole genome sequencing, advanced data analytics, induced pluripotent stem cells, CRISPR/CAS9 genome editing) into a pipeline to accelerate the discovery of causes of disease.

While being highly complementary to local and global genome medicine projects the pipeline will lay the foundation for health-focussed research programs at the Telethon Kids Institute. To demonstrate the utility of our approach we will target children suffering from rare diseases. We will apply a panel of complementary screening technologies to build a molecular portrait of each patient so to discover potential causes of disease. We will validate candidates using patient-derived cell lines or induced pluripotent stem cells (iPSCs). We aim to increase the diagnostic rate for children suffering from rare diseases (currently at 30%) and will explore opportunities for drug repurposing.

Awarded $500,000

Towards the establishment of the PREVAIL Centre, a Centre for PREcision in VAccine ImpLmentation at the Telethon Kids Institute

Tom Snelling, Jason Waithman, Anthony Bosco, Pat Holt, Anita Van Den Biggelaar, Yue Wu, Bree Foley, Marie Estcourt

Vaccines are estimated to have reduced global deaths of infants and children by 95% since the beginning of last century, and continue to save millions of lives a year. However, the mechanisms by which vaccines protect children is poorly understood for many vaccines, and we are still unable to predict how a child will respond to a vaccine. Vaccine failures and adverse events associated with immunisation are a major reason why some parents are reluctant to get their children vaccinated; this poses substantial risk to the on-going success of vaccination programs.

Understanding how and why children respond differently to vaccines is likely to have significant impact on how vaccine programs of the future are implemented. The development of 'omic' technologies in recent years now makes it possible to understand how the whole of a person's body responds to a vaccine and to align this information with how well vaccines protect or cause reactions.

This project value-adds to existing studies being conducted by the Wesfarmers Centre of Vaccine and Infectious Diseases, including a clinical trial looking at infant responses to different types of whooping cough vaccine and their relationship with allergy. This funding allows us to build on this existing work by exploring the transcriptomic and cellular phenomic profiles of infants following routine vaccination. These data will be aligned with clinical outcomes using computational analysis to generate a model for predicting how an individual will respond to a vaccine.

Such models are essential if we are to realise our vision of a personalised rather than a one-size-fits-all approach to vaccination. Establishing a collaboration of clinicians, immunologists and systems biologists across Telethon Kids will harness the strengths of the Institute to make the most of clinical data obtained in infant vaccine studies. The program will initially focus on children with particular disease-risk phenotypes, but will ultimately lead to optimizing health and wellness for all children

"The vulnerable epithelium in cystic fibrosis"

Stephen Stick, Anthony Kicic, Anthony Bosco, Robert Hancock, Paul Watt

A systems biology approach will be utilised to assess the efficacy of current treatment regimens in children with CF. This proposal will provide the opportunity to establish integrated analyses of bioinformatics in CF as well as the development of a personalised screening tool for therapeutic compounds.

Through meta-analysis of omics datasets, molecular signatures will be identified to gain insights into the underlying biological processes of CF. These findings will then be complemented by the generation of stably transfected airway epithelial cells for high-throughput screening of therapeutic molecules to potentially revolutionise the current approach in personalizing treatment for individuals with cystic fibrosis”

"Development of an urgently needed bedside test for diagnosis and monitoring of persistent bacterial bronchitis and bronchiectasis – a pilot study"

Mark L Everard, Dr. Stacey Reinke, Prof David Broadhurst, Michael Bunce, Dr. Andre Shultz, A/ Prof Robert Trengove, Dr Shannon Simpson

The overarching goal of this project is to develop a rapid, non-invasive test for identifying lower airway microbial perturbations associated with bacterial bronchitis.

Timely diagnosis of bacterial bronchitis will prevent the development of long-term morbidity and structural lung damage characterised by bronchiectasis. In participants with already established and irreversible bronchiectasis, we will be able to monitor progress and predict, or even prevent, future exacerbations.

This approach will direct personalised antibiotic treatment of respiratory infections by (1) determining which individuals require antibiotic treatment and (2) ensuring a more appropriate choice of antibiotic (3) allowing for the earlier treatment of infections before irreversible structural airway damage occurs.

For information about the Personalised Medicine Centre for Children, please contact:

Mitali Manzur
Program Coordinator Personalised Medicine
Phone +61 8 6319 1305
Email Mitali

video

Telethon Kids Institute community lecture featuring Professor Leroy Hood