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These are increased in patients with pathological blood clots, such as those causing heart attack and stroke, but are also increased in a blood cancer called essential thrombocythaemia (ET), in which clotting complications are common (40% patients) and responsible for 40% of deaths. Until now, no blood test has been able to predict which ET patients will develop blood clots or progress to fibrosis/leukaemia.

This intellectual property protected assay is performed on standard patient blood samples on a clinical flow cytometer – thus has potential to be adapted for use in diagnostic labs around the world. The additional innovation involves coupling with their novel mathematical algorithm to enumerate a particular sub-population of platelets that appears highly predictive of further blood clots (including stroke) in ET patients.

This project is supported in partnership with The NSW Community Foundation, The NSW Community Foundation – Nicholas and Phillis Pinter Trust, the Vernon Sinclair Fund (all managed by Equity Trustees) and NFMRI. This innovation has successfully gone through a development phase proof of concept and internal validation using blood from ET patients, and funding provided will help support further validation studies across different flow cytometry platforms.

To do so they will modify a new type of retinal camera that they have developed for human use, in order to image the eyes of mice that have been genetically modified to demonstrate features of Alzheimer’s disease. This will enable A/Prof van Wijngaarden and his team to compare their imaging findings in living mice with comparable images from humans and also with mouse retinal tissue studies that will measure the levels and subtypes of amyloid beta. This evidence will be important to gain approval for the use of this imaging technology in the clinic. Doing so would mean that it will be possible to detect people with or at risk of Alzheimer’s disease in the course of routine eye examinations. Detecting the earliest stages of the disease may eventually enable the commencement of disease-modifying treatments at the right time, before irreversible brain damage occurs. 
 
This project is funded in partnership between The Mason Foundation (managed by Equity Trustees) and NFMRI.

 Dr. Ooi then started his own independent laboratory and devised a platform that can genetically engineer GMP-ready Tregs specific for any self-protein. These cell products are called Targeted Tregs.
Dr. Ooi has applied his unique platform to develop Targeted Tregs specific for lupus. Lupus patients suffer from multi-organ dysfunction due to an autoimmune response that attacks its own tissues. Using lupus patient blood samples to devise a novel humanised mouse model of lupus, Dr. Ooi has shown that the lupus-specific Targeted Treg product effectively stops the pathogenic autoimmune response and effectively cures disease.
In addition to the lupus-specific Targeted Treg product (which led to a large research collaboration and commercialisation deal with a multinational pharma company) , Dr. Ooi has developed and filed patents for Targeted Tregs specific for other severe autoimmune diseases including Sjogren’s syndrome and autoimmune vasculitis.
This project is funded in partnership between The Mason Foundation (managed by Equity Trustees) and NFMRI

Both PI3K and BET inhibitors have been developed and show significant clinical activity, particularly in the context of blood cancers. However, the ‘addiction’ of a cancer cell to a particular pathway or process (ie. PI3K, BET) is not absolute. Therefore, the innovation of dual-targeting cancer drugs represents a potential step-change technology, taking the established models of cancer treatment, such as combination therapies, to a new level and attempting to defeat cancers on multiple fronts in a single compound. A dual acting drug puts the two activities in the ‘same place at the same time’, potentially enhancing drug synergy, reducing toxicity and drug resistance. The general concept is gathering traction in the research community and our studies to date of this dual targeting paradigm (PI3K and BET inhibition) shows great promise. 

Prof Shortt and Prof Thompson’s teams have demonstrated that targeting both PI3K and BET proteins together has synergistic anticancer activity, in part due to the ability to prevent cancer cell adaptation and resistance to the inhibition of each target in isolation. NFMRI funding will help support further therapeutic efficacy studies.

Extensive evaluation of this vaccine in mouse models of Zika infection has shown that it induces strong immunity and confers complete protection against systemic Zika infection. Funding from NFMRI is helping to progress the development a novel Zika virus vaccine by completing pre-clinical evaluation of this Zika virus DNA vaccine enabling Phase I Human Clinical Trials, and generating data for regulatory filing. 

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 60-70% of all cases. A major contributor to the spread of AD throughout the brain is the transmission of an abnormally-folded protein called tau. Tau is released from diseased brain cells and taken up by healthy cells, triggering misfolding and aggregation of tau within those cell. Thus, AD spreads throughout the brain. The aim of this project is to engineer an innovative nanotechnology that can target and disrupt tau pathology. If successful, such a strategy would lead to modification of the brain mechanisms of AD and the potential development of a treatment strategy that would be of significant benefit to the millions of individuals currently suffering from AD.

Funding from The Mason Foundation (managed by Equity Trustees) and NFMRI is supporting further engineering of the nanotechnology platform, as well as evaluation of its safety for neurological indications.

 

Prof. Thomas’ team’s work has focused on the cell-surface protein, Angiotensin-Converting Enzyme 2 (ACE2), which all strains of SARS-CoV-2 use like a ‘door’ to access and infect cells of the respiratory tract.  
 
Over the last 16-months, they have discovered and developed an RNA therapy that triggers vulnerable cells of the lungs to preferentially generate soluble ACE2, a short form of ACE2 that can’t be used by the virus to enter the body. Instead it acts as a natural decoy-receptor to prevent SARS-CoV-2 infections. At the same time, the expression of the cell-surface door (ACE2), capable of facilitating virus entry, is reduced by their therapy. They have now proven this novel treatment works to prevent coronavirus infection in lung cells and have also shown that it is highly effective in inducing protective changes in ACE2 in the lungs of healthy mice. They also believe this strategy may also reduce the viral load in infected patients and therein protect people’s health. 
 
NFMRI funding supported proof-of-concept studies, including pharmacokinetic studies, to ensure the best dose can be efficiently and safely delivered using a nebulizer.

to restore communication and independence to those severely paralysed by enabling direct brain control of a computer, Nicholas is now working to expand the potential clinical applications of his technology through development of a Stentrode suitable for efficacious cortical stimulation.  
  
“By combining our ability to record information from the brain with technology that can deliver information to the brain, we can offer hope to treating a wide range of previously untreatable neurological conditions” 

Together with his team, they aim to develop tools that carry the promise of achieving therapeutic efficacy following a single systemic administration of an adeno-associated viral (AAV) vector. Specifically, the project enabled development of two key tools:
(1) novel, human lung-tropic AAV vectors for safe and efficient targeting of the basal cells, which give rise to human airway epithelium (HAE). To increase safety and efficacy, the AAV vectors will be specifically de-targeted from the human liver, which is the primary target of most AAVs following systemic delivery. (2) AAV-based gene editing strategy to correct CF causing mutations in the fibrosis transmembrane conductance regulator (CFTR) gene in the basal cells. 

Combination of those two novel technologies will form the basis of a powerful gene therapy approach to cure cystic fibrosis. The project will also lead to the development of a novel dual liver-lung preclinical model that will enable preclinical studies not only in the area of gene therapy, but also will be an invaluable tool to other researchers studying the disease and/or developing novel therapeutic options for CF. 

Funding provided by the Cure 4 Cystic Fibrosis Foundation and NFMRI is supporting the preclinical validation of the gene therapy approach to cure CF.

with antibodies that recognise these toxic proteins; this is called ‘immunotherapy’. To date, all Abeta immunotherapy trials have had serious efficacy and/or safety concerns, in part because the body’s immune response to the therapy has resulted in inflammation in the brain. Professor Parker and his team have developed a new type of drug that has the advantage that it does not promote inflammation in the brain and can more effectively cross the ‘blood-brain barrier’, a barrier which protects the brain from infection but can also block the transport of drugs. 
 
They have tested the drug in brain cells in the lab and found that their novel drug technology successfully increases the removal of toxic Abeta material without promoting increased inflammation. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI is enabling Professor Parker to complete important pre-clinical trials in animals to take this therapy a step closer to the clinic. This technology holds great promise for future development and has drawn preliminary interest from industry partners. 

Current molecular testing to identify changes in cancer DNA for the above clinical uses is expensive as specialist pathologists and scientists who rely on complex equipment are needed, which often affects patient outcome. It is also slow due to a combination of time for tissue transport to the central test lab and then time taken to perform the assay. The aim of this research was to validate an inexpensive (<$100 compared with $1000s using current technologies), rapid and sensitive method to detect genetic mutations that can be used on blood from patients with any tumour type. The identification of such changes will enable screening, diagnosis, prognosis, selection of patients for particular therapies and monitoring of response to treatment. The basis of the assay is an innovative biosensor that detects the presence of abnormal cancer DNA on binding through a change in electrical current. The novel biosensor method Professor Fox and his team are developing will enable a reduction in the time-critical analyses by days to ensure timely reporting that will help realise the improved outcomes of precision oncology.

Funding provided by State Trustees Australia Foundation and NFMRI has supported further development of the biosensor as well as experiments to delineate the performance characteristics and capabilities of the biosensor to identify different types of mutant DNA.

Two recent studies have provided strong evidence for a potential causal link between the pathogenic oral bacterium Porphyromonas gingivalis and AD. There are also reports of oral bacterial proteolytic enzymes and genomic DNA, particularly those of P. gingivalis and Treponema denticola, in the brain tissue of AD sufferers. Professor Dashper’s and Dr Catherine Butler’s research sought to demonstrate a causal link between specific oral bacteria and the onset and progression of Alzheimer’s disease. If successful, this may open a whole new field of research into the bacterial aetiology of Alzheimer’s disease. 

Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI has enabled further development of this project. 

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).

An additional component for this existing project was approved to enable Dr Lesley Cheng to collaborate with A/Prof Anthony White at the QIMR.

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 are being used to further develop the proof-of-concept of the technology in a preclinical animal model of CF.

Most current therapeutics are only partially effective, providing temporary relief to a subset of patients. There is significant interest in the development of orally bioavailable agents, with more significant and sustained efficacy and which treat a broader IBD patient group. While a number of small molecule immunomodulators are in use or development, the therapeutic utility of these is compromised by their systemic immunosuppressive effects (opportunistic infection and increased cancer risk through reduced immunosurveillance) and off-target effects. Consequently, there is considerable interest in the development of GI-directed agents that can exert a GI-specific immunomodulatory effect. Recently, small molecule sphingosine-1-phoshate-1 (S1P1)-receptor modulators (eg ozanimod and etrasimod) have emerged as a new class of orally bioavailable immunosuppressive agent showing great promise in IBD clinical trials (Phase II/III). However, these agents suffer from dose-limiting adverse effects on non-GI organs. 

Funding from NFMRI is supporting a proof-of-concept to a new class of orally administered, GI-directed S1P1-receptor modulators as more effective treatments of IBD with negligible systemic exposure and improved efficacy and safety profiles. 

These toxic proteins can be removed by a process called autophagy (auto = self, phagy = eat) which is a crucial recycling system within cells. The research group lead by Prof Roger Pocock (Monash University) and co-investigators Dr Patrick Ejlerskov (University of Copenhagen) and Prof David Rubinsztein (University of Cambridge) identified an ancient genetic mechanism that promotes autophagy to reduce neurotoxic aggregate-prone proteins associated with PD and HD. This genetic mechanism was initially identified in a worm model by the Pocock laboratory and subsequently the same mechanism was shown to function in human cells by Dr Ejlerskov when working in the Rubinsztein laboratory. The presence of an identical mechanism controlling the removal of toxic aggregate-prone proteins in distant species (worms and human cells) indicates its importance through evolution. This study was published in the internationally-recognized journal eLife (2019) and the same research group was invited to write a review on this research area in the journal Autophagy (2020). The innovation of this research was the identification of a novel pathway that can be manipulated to remove neurotoxic aggregate-prone proteins that cause neurodegenerative disease. Funding from NFMRI supported the validation of these findings in the brain of a mouse model of neurodegenerative 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 helped develop the therapy towards first-in-human clinical trials for patients with severe heart dysfunction after heart attack.

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. This project was supported by The NSW Community Foundation, The NSW Community Foundation – Nicholas and Phillis Pinter Trust, the Vernon Sinclair Fund and NFMRI. Funding provided helped support clinical validation of the assay in an accredited diagnostic facility.

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 has supported safety and efficacy studies.

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 has enabled retinal camera prototype development and clinical studies to validate the technology against their state-of-the-art research camera. This project was supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees).

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 provided support for the research plan incorporating a rat model and rabbit model study to demonstrate safety and efficacy in two established animal models of vessel injury and healing – key criteria for attracting future investment. These two models would 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 provided the necessary data package to enable investors to confidently drive the technology to the next stage of development and toward clinical translation.

NFMRI supported the validation of 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 were uniquely available via a collaborator already performing human clinical trials for treatment of Malaria infections. NFMRI funding has helped 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 is also expanding 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 was supported in partnership with the generous funding from the NSW Department of Primary industries and NFMRI.

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 sought to 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 supported in vitro toxicity studies for this project.

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 has helping develop the therapy towards proof-of-concept and supporting optimisation, efficacy and safety studies.

Her team has identified that a small sub-population of cancer cells survives various drugs by entering a slow-cycling dormant state. These dormant cells do not proliferate (they sleep) during the therapy, but after the removal of drugs they resume proliferation and continue to grow. A/Prof Munoz and her team have identified a new epigenetic enzyme that enables dormant cells to survive cytotoxic therapy.

IBD (Crohn’s and colitis) results from excessive immune reaction in the gut giving rise to considerable pain and discomfort. If not effectively treated, significant damage can be done to the gut, often requiring surgical intervention. Also, IBD is a significant risk factor for cancers of the alimentary canal. Currently IBD is treated with a variety of different immunosuppressants. These have varying levels of success with different patient groups and a number of these can lose efficacy over time. They nearly all involve broad suppression of the immune system throughout the body. This can have adverse effects, such as increased susceptibility to viral and bacterial infections and increased cancer risk. In this program, we are seeking to develop gut-specific immunosupressants. These will only suppress the immune system of the gut, leaving immune responses elsewhere in the body unaffected. These new drug agents will provide more effective and safer approaches to the treatment of IBD.

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 was 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.

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.

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.

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.

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).

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.

This approach is based on the use of the entire parasite which is made non-infectious by treatment with a chemical agent. For the human malaria parasite (Plasmodium falciparum) vaccine manufacture involves in vitro culture of the malaria parasite followed by chemical treatment. This has since been administered as a single dose to eight volunteers who all developed strong cellular immune responses. Since the vaccine has been shown to be safe and well-tolerated, Prof Good’s team now plans to undertake a Phase Ib trial, which will involve 36 volunteers and test the efficacy of the vaccine. NFMRI funding would help support the vaccine manufacture for this trial. The associated clinical trial and activities are already funded via other sources, including Rotary.

A/Prof Sutton believes that by preventing disruption of this barrier, either before or after H.pylori infection, that they may completely prevent the development of gastritis. A/Prof Sutton wishes to test this vaccine in clinical trials, but to do so he needs to optimise the manufacturing process of the vaccine antigen in order to be able to produce the antigen in sufficient quantity and quality for taking into clinical trials. NFMRI funding will help support optimisation of the manufacturing process for the vaccine antigen. Luinabio, one of the most experienced company in Australia for producing recombinant vaccine antigens used in clinical trials would be contracted by A/Prof Sutton to carry out this work.

Importantly, in experimental systems, reduction in levels of 14-3-3 protein in lung cancer cells has been shown to block cancer cell growth and cause cell death. Therefore, 14-3-3 protein represents a promising ‘molecular target’ for the development of new anti-cancer treatment for lung cancer. Several other laboratories in the world have attempted to generate drugs to interfere with14-3-3, but without much success. Through Dr Woodcock’s research, they have found a novel way to inactivate 14-3-3 protein which already shows greater promise. Based on their knowledge of 14-3-3 protein structure and function, they have identified chemical compounds that selectively inactivate 14-3-3 and have shown that these compounds kill lung cancer cells and reduce lung cancer tumour growth in an animal model. They are currently evaluating these compounds in more relevant models of human lung cancer to assess the potential of our 14-3-3-targeting compounds as anti-cancer drugs for lung cancer. This project is supported thanks to generous funding from the NSW Community Foundation, the NSW Community Foundation – Nicholas and Phyllis Pinter Trust (both are managed by Equity Trustees) and NFMRI. Our combined funding will help support the assessment of pharmacokinetic properties of the drug compounds by scientists at CDCO and analysis of those compounds’ properties using RPPA. These studies will enable Dr Woodwock to fully assess the drug-like properties of those compounds and their potential efficacy for lung cancer.

A vaccine for the Zika virus is urgently required because there is no therapy, and the link with microcephaly in children born to mothers who were infected during pregnancy demands that women of child-bearing potential be immunised. As canonical vaccines (eg. live attenuated vaccines) require a considerable period of development, a DNA vaccine that can be generated in a matter of weeks represents an attractive alternative.In this proposal, Prof. Gowans’ team examine the efficacy of novel DNA vaccines designed to elicit cell-mediated immunity to the Zika virus non-structural proteins or Zika neutralizing antibody in mice. Thus, a major component of the project is to examine the immune responses in mice and pigs, and the protective efficacy of the vaccines in mice, with a view to identifying the most appropriate strategy to further develop for follow up studies in human clinical trials.This project is supported thanks to generous support from the NSW Department of Primary Industries.

These diseases induce excessive levels of hepcidin, which in turn promotes iron storage, thus preventing its release into the blood leading to severe and debilitating anaemia. Prof Richardson has discovered that hepcidin is bound in the blood by a specific protein and has since developed an analogue that leads to urinary excretions of excessive hepcidin. NFMRI support will enable commercialisation of this optimal analogue.

His technology can record brain signals and convert them into useful commands that can be used to control computers, wheelchairs, exoskeletons and/or prosthetic limbs. Translation of existing brain machines is hampered by invasive surgical procedures, which require access the brain and lead to immune reactions that are causing device failure within months. Dr Opie and his team have already done enormous progress since receiving a $1.3m seed funding grant from the Defence Advanced Research Projects Agency – having already developed an implantable stent-electrode array that can record neural information from within a blood vessel, mitigating risks associated with open brain surgery. NFMRI support will help them translate this research into clinical translation via the conduction of a world-first human trial in 2018. To meet this milestone, they must first manufacture the technology in an FDA approved and ISO certified facility and conduct the necessary preclinical experiments to demonstrate reliability, efficacy and safety.

OAC is increasingly common due to growth of the major risk factors: chronic reflux and obesity. Although effective treatments are available for early OAC, outcomes remain poor because most cases are diagnosed at advanced stages due to the lack of practical and effective screening tools. A/Prof Hill has identified and patented a panel of readily translatable glycoprotein biomarkers, which can differentiate OAC from benign conditions and healthy controls. Her research program is in the process of evaluating these markers in large patient samples, as a step toward development of a diagnostic test that can be introduced into clinical practice. NFMRI support helped develop one embodiment of the innovation, the clinical immunoassay. Working with industry partner Precision Antibody, they aimed to generate monoclonal antibodies that recognise the three best biomarkers for use to generate immuno-assays. Successful completion will enable the development of a practical diagnostic test based on our biomarkers.

His team has developed and optimised a series of potent and specific inhibitors of HPGD2S that are orally bioavailable and efficacious in in vivo animal models. NFMRI’s support will provide access to additional research studies and facilities to profile the compounds on human bronchial epithelial cells in order to study respiratory function. These studies will aid in the selection of drug candidates, which will provide efficacious treatment for the cause, not symptoms, of asthma. The funding in particular will provide access to external collaborator Asterand Bioscience in order to accelerate the identification and validation of their drug candidates.

However, the presence of radiotherapy-resistant cells within the tumours of a significant minority of patients can lead to treatment failure resulting in relapse and death. Additionally, there are currently no biomarkers in clinical use which can identify resistant tumours to allow the proper tailoring of radiotherapy treatments to individual patients. Our group seeks to identify and characterise “microRNA” master regulators which control the processes of radiotherapy resistance in breast cancer. In preliminary work we identified a novel microRNA, called miR-1274a, which when at high levels in breast cancer cells significantly increases their resistance to radiotherapy. In the current study we aim to further investigate miR-1274a. We hypothesize that the miRNA itself or the genes that it regulates may be valuable biomarkers of radiotherapy resistance, and therefore could form the basis of diagnostic tests which may be useful in the clinic. In addition, we hypothesize that by treating radioresistant breast tumours with synthetic miR-1274a inhibitors in vivo, we can re-sensitise them to radiotherapy, thereby improving the efficacy of this vital treatment in otherwise recalcitrant tumours.

This research has found that cells surrounded with inflammation appear to move further because the inflammation makes it easier for tumour cells to propel themselves through tissue. The more inflammation in the proximity of a tumour cell, the faster glioblastoma cells travel. This project will make this the first group to report that drugs turning off the activity of an inflammatory protein called MK2 are effective in blocking inflammation in brain tumours. Blocking inflammation may prevent the invasive spread of cancer cells into healthy brain tissue, thus preventing the formation of novel tumours and potentially improving patient’s response to temozolomide (Temodal) during chemotherapy.

Importantly, such therapy can reduce the burden of asthma. However, most vaccines are based on pollens of temperate rather than subtropical grasses. Optimised vaccines based on subtropical grass pollens are needed to provide more specific and effective allergen desensitisation treatment for patients in subtropical regions. Here we aim to utilise our intellectual property and know how pertaining to subtropical grass pollen allergens to develop a new method to measure and standardise the allergen content of subtropical grass pollen allergy vaccine products. The outcomes will have the potential to meet the growing need of patients in subtropical regions of Australia, Asia, Africa and America. An additional utility for this novel method is in outdoor allergen monitoring.

We have made a synthetic version of this molecule and have conducted an extensive array of in vitro studies. Our current data look very promising, and indicate that this molecule targets two enzymes that play a key role in the initiation and progression of Alzheimer’s disease. We believe that this molecule will serve as a template for the development of a whole new class of compounds that could be used in the fight against Alzheimer’s disease. However the in vivo efficacy of the compound we have developed must first be determined. In the studies outlined here-in we will test this molecule in a mouse model of Alzheimer’s disease. Our laboratory currently lacks the technical expertise to conduct these in vivo studies. Therefore we will collaborate with the laboratory of Prof David Small (Menzies Research Institute, University of Tasmania) who is a leading expert in the field of Alzheimer’s disease research.

This collaborative research group has drawn together experts in cardiac fibrosis, cell signalling pathways, enzyme assays, medicinal chemistry and metabolomics to help identify a suitable biomolecular target for fibrosis and to design drug molecules to inhibit this target. The focus has been on a class of lipid signalling molecules called sphingolipids, which control cell functions particularly during infection, inflammation and wound healing. Support from NFMRI will enable A/Prof Flynn to access both internal collaborators such as the Monash Centre for Drug Candidate Optimisation and external collaborators such vivoPharm to assist with targeted studies.

The research is novel and will lead to the development of personalised genomic medicine in which an individual can be uniquely assessed for the likelihood of developing liver cancer, enhance diagnosis, determine the risk of cancer spread and responses to treatment.

Currently, the most effective treatment for cataract is surgery, which involves removal of opaque cellular material and insertion of a plastic intraocular lens into the remaining capsular bag. Although initially effective in restoring sight, a complication of surgery is the development of a secondary cataract. A major focus of this research has been to identify ways of maintaining the normal lens cell phenotypes and provide conditions that promote regeneration of normal lens structure and function. To achieve this goal, greater understanding is required on the factors that maintain epithelial cells and promote their growth and differentiation into the highly elongated and oriented/aligned fibres that determine lens optical properties. In other words, the team needs to find out how to recapitulate normal developmental processes in order to successfully regenerate lenses after cataract surgery.

This promises to maximize the benefit of specific treatments and reduce harmful side effects. A key part of this process is finding biomarkers that predict response to particular treatments. The aim of this research project is to identify biomarkers in lung cancer and mesothelioma that can be used to help select the best treatment for every individual patient. The team is investigating abnormal expression of protein and amplification of genes in lung cancer and mesothelioma that can potentially determine how well a patient will respond to treatment or how quickly or slowly their disease is likely to progress. This research has provided new diagnostic capability at Royal Prince Alfred Hospital and is now scaling up to assist more patients in need.

There is currently no effective treatment for metastatic disease. Recently, a promising new class of anticancer drugs (Histone Deacetylase inhibitors or HDACi that are less toxic than conventional therapies, but can enhance their activity) have been identified. These novel, non-toxic agents may have the potential to improve the management of eye melanoma.This project aims to examine the potential for these agents to be used in eye melanoma sufferers.

In order to design effective strategies for the treatment and detection of glioma, it is important to understand the underlying genetic mutations, which lead to disease. Recent studies have found that the isocitrate dehydrogenase (IDH) gene is mutated in 70-80% of some glioma subtypes, suggesting it may be an early mutation that plays an important role in the development of brain cancer. It is thought that IDH mutations may contribute to cancer by changing patterns of methylcytosine and hydroxymethylcytosine on DNA, thereby changing gene expression to favour cancer development. This study aims to validate this theory by investigating how patterns of methylation and hydroxymethylation change in gliomas, and whether they differ between gliomas with and without IDH mutation.

This promises to maximise benefit of specific treatments and reduce harmful side effects. A key part of this process is finding biomarkers that predict response to particular treatments. The aim of our research project is to identify biomarkers in lung cancer and mesothelioma that can be used to help select the best treatment for every individual patient.

It has now established a potentially major advance in detecting functional loss by utilising the phenomenon of binocular interaction as a means of enhancing early defects. This study will explore this concept extensively and lead to a better understanding of the pathophysiology of early glaucomatous damage by comparing subjective thresholds, objective functional signals monocularly and binocularly, with structural changes all in the same individual. The technique will aid in the diagnosis and management of glaucoma – a disease that currently is one of the 3 most common causes of blindness in the western world. Earlier diagnosis of glaucoma and/or earlier detection of progression would enable earlier institution of appropriate therapy to help preserve vision among our elderly, and would be another step toward reducing the burden of glaucoma-related morbidity in the world.

While unique gene defects have been discovered in some AML types, the cause of the leukaemic transformation remains unknown in a significant proportion of cases. This shortcoming in understanding AML hampers the ability to cure the disease. Abnormal alterations in small regulatory genes called microRNAs have recently been shown to be involved in the development of many cancers. Studies using gene chip technology have uncovered previously unknown abnormalities in microRNAs in unique subtypes of AML. In this study, the research team postulated that microRNAs contribute to the development of subtypes of AML in two ways: by enhancing cell survival and preventing blood cells from reaching maturity. The new knowledge generated by this research will lead to a better understanding of the biology of this rapidly fatal cancer. This may aid in the invention of diagnostic tests and target specific drugs, thus improving patient survival.

However, the tumour cells themselves upset this normal process and so the normal process of so-called immune control is destroyed, or at least suppressed. Prof Joshua and Dr Brown have been trying to identify how this suppression works and to identify ways to allow the normal anti-tumour immune control to be restored. This work has identified several important new mechanisms and has in several cases identified how to correct the deficiencies.