Interferon Epsilon As A Novel Regulator Of Host-bacterial Interaction In Homeostasis, Infection And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$843,088.00
Summary
Gut infections are a leading cause of death worldwide and healthcare use in Australia. Inflammatory bowel disease (IBD) is incurable and affects 1/200 young Australians. Type I interferons (T1IFNs) are important to control gut infections and IBD by interacting with particular bacterial species in the gut. We discovered one T1IFN, IFNε, in human gut. It protects against models of IBD in mice. We will use mouse and human samples to find bacterial or interferon treatments for infections and/or IBD.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Strain-level Characterisation And Visualisation Of The Mucosal Microbial Communities Associated With Inflammatory Bowel Disease (IBD) For The Development Of Novel Biotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$1,181,878.00
Summary
Australia has one of the highest incidence rates in the world of Inflammatory Bowel Disease (IBD), a debilitating inflammatory condition of the gastrointestinal tract. Cutting-edge molecular and visualisation technologies will be used to examine the role of the gut microbiome in IBD, and identify specific members of this community to be used as new therapies to suppress inflammation and improve outcomes for patients with IBD.
A Practice Change For Patients With Severe Chronic, Clinically Unexplained Gastrointestinal Symptoms: A Randomised, Controlled Intervention To Assess Efficacy And Cost-effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$1,276,080.00
Summary
Unexplained chronic gastrointestinal symptoms are extremely common and costly to the health system. Currently patients are managed in the hospital setting with the 'typical' face-to-face office-based model which sees the clinician spending valuable time gathering information and often treatments (e.g. allied health) delivered in a non-standard way. This project will evaluate the effectiveness of a new standard best-practice clinical model with a structured technology enabled management approach.
HTLV-1 is a lifelong infection of immune cells that sustains high infection rates up to 45% in key Australian communities. Despite HTLV-1 causing serious malignancy and inflammatory co-morbidities that shorten lifespan, few biomedical interventions are available. We will examine how the virus grows and alters immune responses to cause disease. With this, we can develop antiviral treatments to reduce virus infected cells, and make new diagnostic biomarker assays suitable for remote settings.
The Role Of Host Proteases In Modulating Enteric Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,267,155.00
Summary
Bacterial pathogens that cause gut diseases result in 2.5 million deaths per year. The gut is a complex environment consisting of numerous factors that must be balanced to maintain enteric health. When these factors are unbalanced, disease can occur, and infections can cause imbalances. This project will increase our understanding of the role that host proteins play in gut infections, providing knowledge critical for developing improved strategies for disease treatment and prevention.
Immuno-metabolic Interactions Of The Fungal Superbug Candida Auris
Funder
National Health and Medical Research Council
Funding Amount
$674,105.00
Summary
Infections threaten hospital patients and undermine our ability to use advanced medical treatments for conditions such as cancer. Candida auris is an emerging superbug causing infections in hospitals and nursing homes that are commonly resistant to front-line antifungal therapy. To build the knowledge foundation for improved treatments, this proposal aims to define how C. auris escapes immune defences and understand the metabolic mechanisms that shape immune responses and infection outcomes.
Antibiotic Potentiators As An Alternative Therapeutic Option For The Treatment Of Extensively Drug-resistant Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$856,858.00
Summary
Antibiotic mono-therapies are increasingly ineffective for hard-to-treat bacterial infections, forcing clinicians to rely on combinations of antibiotics. Our project has identified compounds that have weak to no antimicrobial potency in their own right, yet when combined with an existing antibiotic they potentiate its activity and restore its ability to treat resistant infections. These antibiotic potentiators are exciting alternatives to current therapies with reduced risk of induced resistance
Identifying How The Enteric Nervous System Regulates Gut Permeability In Autism
Funder
National Health and Medical Research Council
Funding Amount
$448,643.00
Summary
This project aims to investigate causes of increased gut permeability in neurological disorders including autism and will apply neuroscience, immunological and microbiology techniques to clarify the causes of increased gut permeability in a well-characterised genetic mouse model of autism.
Targeting Inflammatory Skin Disease Using An Immune-modulatory Human Signal Peptide
Funder
National Health and Medical Research Council
Funding Amount
$698,836.00
Summary
Effective drugs are desperately needed for the improved treatment of inflammatory diseases. We will determine how a modified human peptide, which we have discovered and can make, works to suppress harmful skin inflammation. We will design new formulations to deliver our drug to the skin in order to better treat psoriasis, an autoinflammatory skin disease. We will also trial our new drug in models of atopic dermatitis a debilitating skin disease for which there is limited treatment options.