Current Research

Active Research Projects

Prof Marc PellegriniWalter and Eliza Hall Institute of Medical Research$175,000 over 1 year
Eradicating life-threatening infections in people with cystic fibrosis
The Burkholderia cepacia group of organisms, or microbes, are causing major morbidity and mortality in people living with cystic fibrosis as they have become resistant to most antibiotics. In Australia alone, evolution of drug resistant infections, particularly in the respiratory system, account for 6,300 deaths per year and more than 120,000 hospitalisations per year. These microorganisms, which invade and replicate inside our cells, can be efficiently eliminated by killing the host cell, fundamentally disrupting the microorganisms’ life cycle and rendering the pathogen unable to develop resistance to therapy. Professor Pellegrini’s team at the Walter and Eliza Hall Institute of Medical Research have proven that this can be done without causing collateral damage to tissues or organs.
 
The fundamental breakthrough was identifying a way to specifically kill infected cells and this was achieved by harnessing a mechanism that our bodies naturally use to dispose of unwanted cells called apoptosis, or programmed cell death. Professor Pellegrini’s team has showed that infected cells are completely reliant on a protein called “cellular inhibitor of apoptosis proteins” (cIAPs) for their survival, but that these proteins are dispensable in healthy cells. After years of research, Professor Pellegrini’s team found a class of drugs called SMAC mimetics, which potently inhibit this protein and cause the death of the infected, but not uninfected cells. This mechanism of killing infected cells offers a platform that could be used to treat many types of infection, but the current focus is on treating infections where there is significant resistance to current antibiotics.
 
Funding provided by the Cure4Cystic Fibrosis Foundation and NFMRI will be used to further studies to support and assist with the design of clinical trials.
A/Prof Sarah VreugdeThe University of Adelaide$175,000 over 2 years
A novel treatment for Non-Tuberculous Mycobacteria lung infections in cystic fibrosis patients
Associate Professor Sarah Vreugde is targeting Non-Tuberculous Mycobacteria (NTM) lung infections in cystic fibrosis patients, which cause severe infection and lung function decline. NTM lung disease is caused by bacteria that are common in the environment and are rapidly rising in prevalence, particularly in those with cystic fibrosis. NTM are naturally resistant to antibiotics and even disinfectants and so, are challenging to treat. Sarah’s technology is unique because it is the only treatment in (pre)clinical development that targets the bacterial iron metabolism, which enables the bacteria to thrive and survive.
 
Funding provided by the Cure4Cystic Fibrosis Foundation and NFMRI will be used to further develop the proof-of-concept of the technology in a preclinical animal model of CF.
A/Prof James ChongThe University of Sydney$200,000 over 1.5 years
Development of novel recombinant human platelet derived growth factor therapy for prevention of ischemic heart failure
This project will develop a novel recombinant human Platelet Derived Growth Factor protein therapy for acute ischemic cardiovascular disease. Cardiovascular disease remains our greatest source of death and disability, accounting for billions of dollars in health care costs. The major single cause for this is “heart attack”. Despite significant progress in medical and interventional therapies for heart attack, patients can still lose up to a billion heart muscle cells. This is due to the heart’s inability to regenerate (unlike other organs such as the skin and liver) and down-stream health issues including heart failure, heart rhythm abnormalities and recurrent chest pain occur. A/Prof Chong’s results show that in both rodents and the more clinically relevant porcine model, human PDGF-AB treatment administered after heart attack decreases scar, increases heart function, decreases heart rhythm abnormalities and increases new blood vessel formation. The overarching aim is to progress this experimental therapy into human patients suffering from heart attack and heart failure.  
 
Funding provided by NFMRI will help develop the therapy towards first-in-human clinical trials for patients with severe heart dysfunction after heart attack.
A/Prof Bernard FlynnMonash University$110,400 over 1 year
Sphingosine Kinase-1 inhibitors for the treatment of pulmonary hypertension
Pulmonary hypertension is a major unmet medical need. A significant body of evidence from a number of different research groups has implicated a certain class of lipids called sphingolipids as key drivers of pulmonary hypertension progression. In particular, the enzyme known as sphingosine-kinase-1 (SK1) which produces a sphingosine-1-phosphate (S1P) is of particular relevance to pulmonary hypertension. A/Prof Flynn’s group has generated inhibitors of SK1 that are both more selective and more “drug-like” (able to be administered orally) than existing agents representing a safe and effective means of treating pulmonary hypertension.
 
Funding provided by NFMRI will help develop the therapy towards proof-of-concept and will help support optimisation, efficacy and safety studies.
Dr Wei DengUniversity of New South Wales$101,825 over 1 year
Nanostrategy for X-ray triggered chemotherapy towards rectal cancer treatment
This innovative technology stems from Dr Weng’s research that photodynamic therapy (PDT) agents can be triggered by low dose X-ray radiation. The stimulated PDT agents produce active species which destabilise liposome structure. Inspired by this discovery, her team creatively combined two existing clinical techniques used in cancer treatment – radiation and chemotherapy through a nanoparticle drug delivery mechanism. The innovative aspect of this technology is the radiation-triggered instant drug release from the liposomes at the tumour site. Using very low radiation doses, the drug is released and becomes significantly more toxic to cancer cells than current administration. What’s more, as cytotoxic drugs can only be released within the radiotherapy field (confined to the tumour site), any toxicity to other healthy tissues is largely reduced.

In this manner, this technology has demonstrated impressive anticancer efficacy in a mouse model by one-dose injection and single irradiation. This innovation will be applicable to treat deep tumours due to high penetration depth of radiation.

Funding provided by NFMRI will help support safety and efficacy studies.
Dr James Blackburn Garvan Institute of Medical Research$144,865 over 2 years
Improving sarcoma cancer diagnostics through implementation of a novel fusion gene test
This innovation consists of the development of a clinical test for fusion genes in sarcomas and other solid cancers – the Solid FuSeq test – that surpasses the performance of molecular diagnostic assays currently employed in standard pathology labs. Using multi-gene sequence enrichment, this broad-spectrum assay screens for all fusion gene events in a single test while detecting individual fusion genes with high sensitivity. The Solid FuSeq test also facilitates the discovery of new fusion events and therefore potentially novel therapeutic targets. Whilst sarcoma patients would be the first to benefit from this innovative molecular diagnostic, the Solid FuSeq assay is designed such that all solid tumour cancer patients would benefit from the assay.

Funding provided by NFMRI will help support clinical validation of the assay in an accredited diagnostic facility.
A/Prof Nuri GüvenUniversity of Tasmania$144,300 over 2 years
Pre-clinical assessment of toxicity to select drug development candidates against mitochondrial dysfunction
While more than 90% of cellular energy is produced by mitochondria, dysfunctional mitochondria lead to organ failure, disease and even death. Dysfunctional mitochondria are associated with a vast number of diseases and conditions, ranging from neurodegenerative and metabolic disorders to inflammatory conditions, cancer and ageing in general. Despite this prevalence in a multitude of diseases, there is still a striking lack of approved drugs that aim to directly restore mitochondrial function. This project will select drug development candidates from a novel class of short-chain quinone compounds developed at the University of Tasmania.  These new compounds effectively protect cells against mitochondrial dysfunction. More importantly, two of those compounds effectively protect against disease pathologies in several unrelated rodent models associated with mitochondrial dysfunction.

Funding provided by NFMRI will help support in vitro toxicity studies.
Dr Peter van WijngaardenCentre for Eye Research Australia$250,000 over 2 years
Translating an eye imaging biomarker for Alzheimer’s Disease to the clinic
Dr Wijngaarden’s research group has recently developed a novel imaging method that allows them to non-invasively detect the accumulation of amyloid beta in the retina. Their research has utilised a state-of-the-art, costly camera that images the retina sequentially with 90 different wavelengths (colours) of light. They have identified that 3 wavelengths of light carry most of the amyloid beta signal, suggesting that a modified, low cost retinal camera may be used as a screening test for Alzheimer’s disease. NFMRI funding will enable retinal camera prototype development and clinical studies to validate the technology against their state-of-the-art research camera.

This project is supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees).
Dr Lesley ChengLa Trobe University$75,300 over one year
Specificity testing and cross-laboratory validation of a blood test for Alzheimer’s Disease
This research aims to accurately detect Alzheimer’s disease (AD) within a time-frame to allow positive lifestyle changes and ultimately therapeutic intervention. The work is based on the discovery that small vesicles, called exosomes, are released from cells acting as distinct indicators of the health status of the tissues from which they derive. Exosomes thus represent disease biomarkers. The novel hypothesis surrounding Dr Cheng’s research is that exosomes secreted from brain tissue migrate across the blood brain barrier into the blood where brain biomarkers are readily detected. This is equivalent to a ‘liquid biopsy’ of the brain reflecting neurological status. In preliminary studies she has already identified a panel of 16 serum exosomal miRNAs that are altered in AD compared to heathy patients. NFMRI funding will help validate the specificity of these potential AD biomarkers. Therapeutic strategies aimed at limiting neurodegeneration and improving quality of life in AD require methods to diagnose and monitor the disease in pre-clinical patients. Currently, definitive diagnosis of AD is only possible post-mortem or through PET neuroimaging that requires expensive equipment, highly trained operators and cerebrospinal fluid (CSF) collection. In comparison, blood is a conveniently collected, less-invasive source of biomarkers. Funding will enable this critical work to go full term and be translated to a reliable, economically viable, routine pre-clinical AD screen.

This project is supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees).
A/Prof Anthony WhiteQIMR Berghofer Medical Research Institute$100,000 over 1 year
A personalised medicine approach for screening neuroinflammatory drug efficacy in Alzheimer’s Disease
A/Prof White’s team has developed a unique approach to screening drugs that target the brain’s resident immune cells (microglia) on a person-by-person basis. They are able to generate microglia from a person’s blood cells (monocytes) in 2 weeks at a cost of ~$50/person. These cells can be screened for the ability of different drugs to enhance their protective functions, allowing them to determine which drugs will likely benefit each patient. With access to large Alzheimer’s disease cohorts they are in a unique position to establish a screening platform for patient-specific drug efficacy, allowing physicians to prescribe a drug treatment regime tailored to an individual’s own microglia. Patient microglia responses can then be monitored over time. NFMRI funding will support research to screen patient specific potential drugs.

This project is supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees).
Dr Sanjaya KuruppuMonash University$90,000 over one year
Improving the efficacy of a new venom-derived drug for Alzheimer’s Disease
Dr Kuruppu’s preliminary data demonstrates that administration of his team’s originally discovered peptide can prevent the formation of amyloid beta plaque. Inability to get peptides across the blood brain barrier is a significant factor that impedes the development of drugs for neurodegenerative diseases. Previous studies have shown that L-arginine can improve the blood brain barrier permeability of drug leads. This research grant will enable Dr Kuruppu to determine if co-administration with L-arginine will facilitate the uptake of the peptide by the brain, thereby preventing amyloid beta build-up and associated behavioural changes. The results of this study can add significant value to their original discovery helping to fast track it towards the clinic.

This project is supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees).
Prof Roger ChungMacquarie University$183,488 over 1 year
Preclinical evaluation of novel therapies for clearance of TDP-43 in amyotrophic lateral sclerosis
Professor Chung’s team recently identified mutations in a specific gene (CCNF) as the cause of amyotrophic lateral sclerosis (ALS) in a large Australian family. A number of different mutations in the CCNF gene were identified by their international collaborators, and more recently by other international research groups. CCNF encodes a component of the protein that is a central regulator of protein degradation within cells. Because abnormal accumulation and aggregation of a protein, called TDP-43, inside motor neurons is the key pathological hallmark of the disease, it is possible that defective CCNF might contribute to a common convergent mechanism that leads to the abnormal protein aggregation that causes ALS.

To explore this further, Professor Chung’s team have successfully undertaken further experiments and screening. The data generated from these experiments and screenings has provided compelling evidence.

NFMRI funding would be used towards a study that will provide strong pre-clinical evidence of efficacy for a proposed gene therapy.  This is essential data for advancing this innovation through commercial development.  This discovery is currently protected through a PCT that is due for conversion to National Phase in 2019, and potential commercial investors (pharma etc) that they have approached have indicated that positive indications in a pre-clinical mouse study are required before they can consider the innovation for investment.
Dr Clare Stirzaker
Garvan Institute of Medical Research
$141,834 over one year
Liquid biopsy monitoring for triple negative breast cancer: a novel epigenetic test
Dr Stirzaker and her team have performed the FIRST genome-wide profiling study on DNA methylation (epigenetics) in Triple Negative Breast Cancer (TNBC). Funding from NFMRI would be used to develop this TNBC-specific blood-based biomarker test, by providing access to the sensitive methylation assay that has been developed in the laboratory of Prof Trau and Dr Korbie at the University of Queensland. This assay is particularly important as it allows, for the first time, up to 50 methylation signatures to be tested on the same clinical sample in one test. In addition, the test employs next-generation sequencing which allows unprecedented sensitivity to be achieved, critical to accurately detect tumour methylation in a blood sample when circulating tumour DNA may comprise only 1% of the total circulating free DNA.

This project is supported in partnership with the generous funding from the NSW Community Foundation, the NSW Community Foundation – Nicholas and Phyllis Pinter Trust (both are managed by Equity Trustees) and NFMRI.
Dr Adam Taylor
Griffith University
$50,000 over 1.5 years
Liposome delivery of a chikungunya virus vaccine candidate: a solution to vaccine production bottlenecks
Dr Taylor has had several partnering discussions with industry around licensing or co-development of their live-attenuated chikungunya virus (CHIKV) vaccine candidate. This highlighted a single barrier for investment: production limits. The modifications that make the virus safe and effective for use as a vaccine, prevent rapid, large-scale production of the virus. It simply doesn’t replicate fast enough. In response to this feedback, they have developed an alternative vaccine delivery vehicle that removes the need for in vitro scale up, and therefore, removes the production limit. NFMRI funding will enable conduct of efficacy testing on the new formulation to confirm immune response and storage efficacy. This type of late pre-clinical research activity is not typically funded through NHMRC, but is critical to obtaining the required data to entice an industry partner, and consequently, bridge the ‘valley of death’. CHIKV is transmissible between animals and humans via a mosquito vector. As global temperatures are rising, the mosquito populations in South-East Asia and Queensland are migrating south and their prevalence in New South Wales is increasing.

This project is supported in partnership with the generous funding from the NSW Department of Primary industries and NFMRI.
Dr Steven Wise
Heart Research Institute
$95,022 over one year
Durable treatment of peripheral artery disease
Dr Wise is seeking support for an injectable treatment for peripheral artery disease. Peripheral artery disease has a significant impact on the health of humans, affecting over 2.3 million Australians and 200 million people globally. There is currently no lasting effective treatment, and thousands of cases result in amputations each year. This intervention has the potential to provide an urgently needed improved treatment option.

NFMRI funding provides support for the one-year research plan incorporating a rat model and rabbit model study that will demonstrate safety and efficacy in two established animal models of vessel injury and healing – key criteria for attracting future investment.

These two models will complete the optimisation and proof-of-concept stages for the technology (rat model), before going head-to-head with current clinical practice in arteries of increasing anatomical similarity to humans (rabbit). Together these studies will provide the necessary data package to enable investors to confidently drive the technology to the next stage of development and toward clinical translation.
A/Prof Joanne Macdonald
University of Sunshine Coast
$140,550 over 1.25 years
A rapid, sensitive and portable molecular genetic test for diagnosis of Malaria in blood
In a project previously funded by the Bill and Melinda Gates Foundation, A/Prof Macdonald and her team developed rapid assay technology for the detection of Malaria (Plasmodium falciparum) in mosquitoes. Support is now required to validate the rapid and sensitive Malaria test for detecting subclinical infection levels at a collaborating institute by testing it on human samples containing low levels of infection. These samples are uniquely available via a collaborator already performing human clinical trials for treatment of Malaria infections. If it can be demonstrated that the test has higher sensitivity and can detect subclinical parasite levels, then the test will be well positioned to attract funding and investment for development into both the clinical detection market, as well as the market for tests that can assist with community screening for eradication programs.

NFMRI funding will also help to determine the optimal manufacturing reagents to achieve the best possible sensitivity, specificity and reliability of testing kits, to provide further confidence for potential investors that our test can be reliably manufactured. The team will also expand the assay to detect other malaria strains such as P. vivax, which will extend the number of countries the tests can be employed in, as the relative prevalence of Plasmodium strains differs between countries.

This project is supported in partnership with the generous funding from the NSW Department of Primary industries and NFMRI.
A/Prof Janet DaviesQueensland University of Technology$99,953 from 2018 to 2019
Point of care diagnosis for hay fever and asthma; development and validation of rapid subtropical specific IgE tests
This project proposes to use allergen molecules of subtropical grass pollen for more specific tests and treatments to assist people allergic to grasses in subtropical regions. Approximately 15% of the Australian population suffers from allergic diseases and the devastating effect of such allergies was felt in the recent thunderstorm asthma event in Melbourne where over 12,000 people were affected and 9 reportedly died. After identifying and characterising all the key allergens of two major subtropical grass pollens and making headway in subtropical grass pollens research, A/Prof Davies is proposing to partner with Abionic SA, a Swiss company that has developed an instrument that quickly measures levels of sensitivity to allergens in doctors’ rooms, to investigate whether recombinant version of their pollen allergens are effective as a more specific and rapid point of care diagnostic test for grass pollen allergy in warmer regions of the world. NFMRI funding would help support optimal generation and purification of two quality assessed recombinant allergen components, as well as trialling these component on a new point of care diagnostic platform. The pre-commercial research will advance the innovations quickly for commercial uptake.

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