Understanding and preventing disease
Understanding and preventing disease
Research underpins our knowledge of disease. Understanding history, sociology, ethics, biology, chemistry and physics is critical to the management and prevention of disease.
La Trobe researchers work in partnership with bioscience institutes, health providers, industry and government to make discoveries in fundamental sciences that improve diagnostics, therapeutics and clinical outcomes across a range of diseases.
La Trobe's research into Understanding and Preventing Disease contributes to the following United Nations Sustainable Development Goals (SDGs)
Selected impact stories
Leading Team: Eliza Hawkes, Jodie Palmer, Alexandra Romano
Follicular Lymphoma (FL) is a type of slow growing blood cancer that affects lymph nodes and the lymphatic system, parts of the immune system that are integral to fighting disease. As patients with FL are predominantly aged over 65 and may require treatment multiple times over their disease course, novel regimens which maintain or enhance efficacy and minimise toxicity are highly desirable. The TOP-FLOR trial (NCT05788081), led by the Olivia Newton-John Cancer Research Institute (ONJCRI) in collaboration with Bristol-Myers Squibb, is investigating a new combination of immune system activating therapies to see how effective this combination is in patients who have had no previous drug treatment for their Follicular Lymphoma. The trial aims to reduce treatment side effects and improve long-term treatment effectiveness for patients.
Leading Team: Oliver Klein, Jodie Palmer, Kylie Wilkie, Andreas Behren, Jonathan Cebon
Whilst rare cancers make up more than 20% of all cancer diagnoses, they are individually very rare (~2/100,000), and treatment options for patients are limited. Challenges to accessing clinical trials and new treatments related to rare cancers are particularly acute for Australians living in rural, regional and remote areas (a third of Australians). The MoST CIRCUIT trial for advanced rare cancers is led by the Olivia Newton John Cancer Research Institute (ONJCRI). Thanks to ONJCRI’s collaboration with the ReViTALISE project, Omico MoST program, Minderoo foundation and Australian Teletrial Program, the trial has provided access to patients in regional and rural areas who would not normally have accessible treatment options. Building on findings from an earlier 120 patient study, 240 Australian and New Zealand patients have been enrolled, with the aim of identifying and confirming a clinically effective treatment for rare cancers using the immune stimulating anti-cancer drugs Ipilimumab and Nivolumab. In 2023, the Rare Cancer Leadership Team at ONJCRI were awarded the Victorian Comprehensive Cancer Centre (VCCC) Alliance’s Outstanding Changemaker award.
Leading Team: Jacqueline Orian
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system which can cause symptoms ranging from numbness and weakness to an inability to walk. It affects over 30,000 people in Australia. The mechanisms underlying neurodegeneration, or nerve loss in MS are not well understood. La Trobe researcher Jacqueline Orian established a new paradigm for understanding the mechanisms behind MS by asserting that platelets play a neurodegenerative as well as neuroinflammatory role, opening the possibility of using novel strategies for platelet-targeted treatments to tackle the disease. Orian and her team developed a new laboratory model that better represents the disease, tweaking the induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE) to slow its rate of progression in mice. By studying this model Orian and her team confirmed the entry of platelets into the brain and spinal cord and found that platelets are drivers of inflammation and neurodegeneration. In collaboration with Professor Peter from the Baker Institute and with funding from MS Australia, the Orian laboratory demonstrated that a novel drug (originally created at the Baker Institute to treat atherosclerosis) specifically targeting disease-associated platelets can halt disease progression. Given that inflammation is fundamental to autoimmune diseases (including rare diseases), platelet targeting drugs have broad therapeutic potential which Orian is now focussed on investigating.
Read more about the Orian Neurodegenerative diseases Research Group
Leading Team: Nick Reynolds
Dr Nick Reynolds – a member of the La Trobe Institute for Molecular Science - has spent 15 years researching protein aggregation, in which damaged proteins bind together into masses known as amyloids. Amyloids are the molecular hallmark of a number of neurodegenerative diseases including Alzheimer’s and Parkinson’s. But in 2022, Reynolds and collaborators from Swinburne University of Technology, Peter MacCallum Cancer Centre, ETH Zurich and the University of Luxembourg published a paper in Nature Communications which was one of the first to propose the role of aggregated amyloid proteins in triggering the neurological effects associated with COVID-19. The paper contributed to the development of a new field of enquiry in relation to virus development, in which amyloid structures and the associated inflammation that they cause had previously been overlooked. With funding from the EU Joint Programme on Neurodegenerative Disease research (JPND), the group of collaborators, led by Josh Berryman from the University of Luxembourg, formed CovAmInf, an international working group whose function is to advise the European Union on the developing research and understanding of novel coronavirus SARS-COV-2 infection, amyloid diseases, and chronic inflammation, so that this science can be used to shape scientific priorities and public policy in the future. The group recently published SARS-CoV-2 infection as a cause of neurodegeneration in The Lancet: Neurology, a summary and analysis of clinical data from the past five years.
Leading Team: Andreas Behren and Ashleigh Poh
Lung cancer is the leading cause of cancer death in Australia. It is rarely detected early due to the lack of a screening program, with 80% of patients presenting with inoperable metastatic disease. The lack of access to tissue has limited researchers’ ability to study lung cancer, improve outcomes and overcome the greatest challenge in relation to metastatic lung cancer, which is the development of resistance to treatment. The Olivia Newton-John Cancer Research Institute ONJCRI (La Trobe University’s School of Cancer Medicine) is leading a $4 million project Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance (TRACKER) to create Australia’s first advanced lung cancer biobank with funding from the Australian Government’s Medical Research Futures Fund (MRFF) and in kind support from project partners and supporters across Australia.
The project was conceived and developed by clinician-scientists Dr Tracy Leong and Dr Sagun Parakh (Austin Health), researchers at the ONJCRI (Associate Professor Andreas Behren, Head of the Tumour Immunology Laboratory and project lead, and Postdoctoral Research Fellow Dr Ashleigh Poh), the Peter MacCallum Cancer Centre (Dr Stephen Wong) and the Walter and Eliza Hall Institute (WEHI). It has been co-designed and developed by consumers with lived experience from the onset. Their impact can be seen in the design of the non-surgical and a minimally invasive approach to acquiring samples through endobronchial ultrasound, liquid biopsies, and the collection of bronchoalveolar lavage fluid, providing valuable biospecimens for research in cases where patients would not have undergone surgical biopsies. These samples will be collected over the course of a patient’s cancer journey, from initial diagnosis and throughout their treatment, providing a unique longitudinal bio and data bank which will allow researchers to investigate the dynamic changes in cancer behaviour under treatment pressure leading to treatment resistance.
Collection and research sites for TRACKER include hospitals in Victoria, New South Wales , Queensland, South Australia and Western Australia which will build on the number and type of samples available for analysis. Samples will be logged in a virtual biobank, making them available to researchers on request for analysis. All applications are reviewed by the consumer committee to ensure that the projects align with the interests of patients. The data generated by research using biobank samples must also be shared and fed back into the biobank database so that it can be accessed for future research, avoiding the siloing of information. Making the samples available to centres and researchers nationally leverages collaborative expertise in analytics and infrastructure. All samples are collected, stored and processed in such a way that they can be analysed using any methodological approach, allowing centres to generate results using specific analytical approaches - genomics, transcriptomics, epigenetics, and proteomics – which can then be integrated and harmonised as a multi-omics dataset through the biobank with the aim of more rapidly identifying novel biomarkers and targets for therapeutic approaches.
Leading Team: Begona Heras and Jason Paxman
Antibiotics have proved revolutionary in the treatment of disease and infections, but their use places an evolutionary pressure on bacteria to adapt and survive, increasing rates of antimicrobial resistance and raising fears of the next pandemic. Research led by Professor Begona Heras at La Trobe University is investigating innovative methods for combatting major WHO declared pathogens through understanding virulence factors – the molecular weaponry of pathogens which allow them to evade and resist treatment - at the molecular scale. A particular group of proteins Heras is investigating are involved in the development of biofilms – structures which protect bacteria from antibiotic activity and which are responsible for up to 80% of persistent infections in humans. In this context, Heras’ patented discovery of the role of a key autotransporter protein in biofilm formation and the development of molecules that inhibit this scaffold protein that block biofilms opens up the possibility of developing further inhibitors which can be used against pathogens which carry these proteins, including E. coli, the primary contributor to anti-microbial resistance related deaths in humans. The goal of this approach is not to kill or stop the replication of bacteria (as with antibiotics), but rather to disarm the pathogens so that they can be cleared effectively by our immune system.
Leading Team: Joseph Tucci
Antibiotic resistance is one of the biggest problems facing medicine today. One possible solution is the use of bacteriophages - viruses that specifically attack bacteria, as therapeutic agents. The La Trobe team led by Professor Joseph Tucci have isolated and characterised bacteriophages against bacteria which give rise to periodontitis, diabetic ulcers, pneumonia and sepsis. Some of these bacteria are also oncobacteria known to worsen breast cancers, colorectal cancers, and gastric cancers. Professor Tucci is collaborating with the Olivia Newton John Cancer Research Institute, the Melbourne Dental School, Flinders University, and International partners, on translation pathways for this work, which is being progressed to animal models, representing a significant step in the preclinical pipeline. Another innovation by Professor Tucci’s lab is a novel assay for detecting levels of endotoxin in bacteriophage formulations. It is more robust and sensitive, as well as significantly cheaper, than commercial alternatives. Following publication, it is likely to be adopted for use in clinical trials involving bacteriophages.
Leading team: Kevin Huynh, Peter Meikle, Corey Giles and Amy Liang
Lipidomics involves the use of mass spectrometry to identify and profile the abundance of different lipid species, a diverse series of hydrophobic and amphiphilic molecules that are central to all of biology. Lipids diversity span hundreds of defined classes and subclasses, with thousands of individually unique species. In human plasma, lipid profiling can be used to better understand changes to metabolism in health and disease.
One of the challenges of lipidomic analysis – as with early Whole Genome Sequencing (WGS) – is that comprehensive profiling of the thousands of lipids and lipid sub-classes can be a costly, time and resource intensive endeavour. The Baker Department of Cardiovascular Research, Translation and Implementation at La Trobe features the only high-throughput lipidomic platform in Australia, and has performed some of the largest reported clinical and population lipidomic studies. However the current analytical throughput still limits the feasibility of lipidomics in larger (n > 10,000) studies.
A research team including Kevin Huynh, Peter Meikle, Corey Giles and Amy Liang is developing a high throughput methodology which substantially increases the speed and efficiency of the lipidomics process, without losing biological information. A machine learning pipeline and reference library is being developed which will derive the full coverage of the plasma lipidome, from a short, 2-minute sweeping mass spectrometry scan. This reference library will be generated using plasma from 10,000 people, whilst the models developed to extrapolate results from this data will be tested against a further 5,000 people. Subsequent new samples would only need 2-minutes to perform the lipidomics profiling.
The methodological approaches developed at the Baker Department are already included as application notes for liquid chromatography mass spectrometry products sold by Agilent – a global leader in advanced scientific instrumentation operating in over 110 countries – in order to sell their instruments. The new machine learning models being developed at the Baker will remove existing limitations on the rate at which samples can be profiled at scale, allowing a better understanding of the relationship between lipids and disease.
Leading team: Professor Katherine Harding and Professor Nicholas Taylor
Many patients face long waiting times for outpatient and community health care. Waiting for services can result in physical deterioration and reduced engagement in services, and has also been associated with anxiety and decreased levels of community participation. The model developed by the La Trobe team, known as “Specific Timely Appointments for Triage” or STAT, targets clinics providing outpatient services over multiple appointments in community settings. STAT has been successfully implemented by service providers across states in Australia and New Zealand, and has consistently reduced waiting time by 20-40%, with some services reporting to have eliminated waiting lists.
Over the last 2 years (2021-2023) the Victorian Department of Health commissioned a review of the Demand Management Framework for Community Health. The old framework, which relied heavily on an outdated emphasis on triage tools, has been replaced by a new Demand Management Toolkit which draws on the principles of the STAT model and advocates its use as a way to manage demand for these services. Following receipt of a $200,000 by the Department of Health Victoria to support the implementation of the new Toolkit, the La Trobe University / Eastern Health team are conducting a series of workshops throughout 2024 for community health providers across Victoria, supported by a suite of resources, and an online community of practice for clinicians to work together to reduce health service waiting times. PhD student Kate Noeske will run a program of research alongside this implementation project, investigating how the model works when implemented at scale.