Investigation Into The Roles Of Ena/VASP-Like And Protein Phosphatase 4C In DNA Damage Repair Via Homologous Recombination
Funder
National Health and Medical Research Council
Funding Amount
$57,139.00
Summary
The repair of DNA damage is a critical cellular mechanism that exists to ensure genomic stability. This project aims to investigate the role of the proteins Ena/VASP-Like and Protein Phosphatase 4C in DNA damage repair via homologous recombination. The DNA damage response pathway is an important area in the study of cancer and ageing, and the potential role of PP4C and EVL in homologous recombination needs to be investigated further.
Characterisation Of Two New Kinases In The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$550,602.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Gish and Fray kinases control tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
Role Of Oxidative Stress In Activating ATM To Protect Against Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
ATM is the protein defective in the human genetic disorder ataxia-telangiectasia (A-T). This project is designed to investigate how this protein is activated by oxidative stress. The study is largely a mechanistic one, to investigate changes occurring in ATM as part of the activation process. There is evidence that ATM exists in the cytoplasm in neuronal cells and understanding its function in these cells may assist in understanding the basis for neurodegeneration in A-T.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and ....Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and immune cell death via the non-canonical inflammasome. We do not currently understand how some immune pathways are turned on or off. This project will yield fundamental insight into mechanisms of mammalian inflammasome, inflammation and anti-microbial responses.Read moreRead less
The overall goal of the program is to develop novel approaches to slow the progress or prevent neurodegeneration in patients with rare human genetic disorders. The second program is designed to develop novel therapeutics from snake venom proteins. These include proteins with anti-bleeding activity and those with application in wound healing. The third program involves the development of novel biomarkers for the early detection and prognosis in prostate cancer.
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