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.
Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Discovery Early Career Researcher Award - Grant ID: DE180101075
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understandin ....Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understanding of the biological mechanisms that protect the central nervous system from harmful inflammation and thus improve our knowledge of the immunobiology of the brain and eye.Read moreRead less
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
Designing new generation adjuvants for allergy and parasite vaccines. Allergy vaccines have the potential to provide a permanent cure against many allergic diseases, currently affecting 20-30 per cent of people in developed countries. This project will study how allergy vaccines work and how we can improve their effectiveness and safety.
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
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
Controlling apoptotic cell death in health and disease. Regulating how and when cells die is crucial for the development and maintenance of a healthy body and mind. This project will investigate the proteins that are responsible for controlling cell death with the view to identifying novel ways to target these proteins for the treatment of disorders such as cancer, neurodegenerative disease and autoimmunity.