Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Targeting Cytokine Signalling In Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$917,626.00
Summary
Systemic lupus erythematosus is a disease where the immune system attacks normally healthy tissues. The spontaneous overproduction of signalling molecules called interferons in lupus plays an important role in the severity of the disease. We have found that two proteins, named Bcl6 and PLZF, are important in controlling the interferon response in lupus patients. We propose that identifying how these proteins act to control interferon will aid in developing new treatments for lupus.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100066
Funder
Australian Research Council
Funding Amount
$440,000.00
Summary
Mass Cytometry: A breakthrough in multidimensional systems biology. Mass cytometry - a breakthrough in multidimensional systems biology: Mass Cytometry by Time of Flight marries the resolution, specificity and sensitivity of atomic stable isotope mass spectrometry to the high-throughput, single-cell analytical advantages of flow cytometry. Using molecular probes conjugated with stable isotope tags, a large increase is possible in the number of simultaneous quantitative measurements in complex sa ....Mass Cytometry: A breakthrough in multidimensional systems biology. Mass cytometry - a breakthrough in multidimensional systems biology: Mass Cytometry by Time of Flight marries the resolution, specificity and sensitivity of atomic stable isotope mass spectrometry to the high-throughput, single-cell analytical advantages of flow cytometry. Using molecular probes conjugated with stable isotope tags, a large increase is possible in the number of simultaneous quantitative measurements in complex samples. These parameters, denoting cell type, function and signalling status, will make possible future advances in the understanding of the diversity of cell phenotype and function with a systems biology approach. Read moreRead less
Control of cell fate decisions in neurogenesis: use of embryonic stem cells to investigate key signalling systems and gene expression programs. Human embryonic stem cells (hESC) have the potential to provide an unlimited source of specific subtypes of human neurons for basic studies in neuroscience and biomedical applications. The use of hESC is limited at present by a lack of control over lineage commitment during differentiation in vitro. This project will use engineered reporter hESC lines t ....Control of cell fate decisions in neurogenesis: use of embryonic stem cells to investigate key signalling systems and gene expression programs. Human embryonic stem cells (hESC) have the potential to provide an unlimited source of specific subtypes of human neurons for basic studies in neuroscience and biomedical applications. The use of hESC is limited at present by a lack of control over lineage commitment during differentiation in vitro. This project will use engineered reporter hESC lines to investigate which cell signalling pathways and gene expression programs are involved in controlling cell fate. The project will result in improved protocols for hESC differentiation allowing enrichment of cultures with specific neuronal subtypes, and significant advances in the understanding of neuronal lineage commitment and maturation during brain development. Read moreRead less
How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth contr ....The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth control, cell fate specification, cellular signalling and eye vision. These discoveries are likely to enhance international collaborations and stimulate new research.Read moreRead less