Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
Solving the puzzle of complex disease - genes and their interactions with the environment. Many human diseases are caused by the interplay of genetic predisposition (nature) and the environment (nurture); but their causes remain a mystery, since much past research has focused on these aspects in isolation. This project will aim to better understand these complex diseases using a multi-factorial approach that brings both nature and nurture together.
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100537
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neural regulation of immunity following brain injury. Following a brain injury, the brain tries to protect itself by blocking all inflammation. However, this renders the host with impaired immunity and increased risks to infections. The project aims to delineate the mechanisms behind this response, with the expected outcome of highlighting the important interplay between the nervous and immune system.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100210
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
In-vivo, high-resolution, whole animal imaging . The purchase of state-of-the-art live-animal imaging equipment for use by researchers at The Australian National University and The University of New South Wales. This equipment will aid the study of many aspects of normal biology and disease including cancer, inflammation, autoimmune diseases and blood vessel disorders.
Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Building child health through maternal wellbeing. Chronic diseases partly originate in the health & social circumstances of previous generations, during pregnancy, and in conditions during infancy and childhood. This project will draw from three community studies the researcher established to investigate how aspects of women's health affect their children's health and identify new opportunities for disease prevention.