Testing A Combination Of 2 Clinical Drugs, An IAP Inhibitor And P38 Inhibitor, To Treat AML
Funder
National Health and Medical Research Council
Funding Amount
$200,890.00
Summary
Current treatments only cure 50% of Acute Myeloid Leukaemia (AML) patients, and novel approaches to treatment are desperately needed to improve survival of patients with leukaemia. One new drug, Birinapant, is currently being tested in clinical trials to treat AML. I have found that some AMLs are resistant to Birinapant treatment but the addition of a second drug (called “p38 inhibitors”) can now overcome this resistance. I will test how effective combining these two drugs can be to treat AML.
Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and p ....Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and plasticity in the T cell antigen receptor (TCR) network; and infer rules linking spatial organisation and signalling activities in intact T cells. Contextualising the TCR signalling network is expected to reveal the origin and use of network plasticity for T cell decision-making. Such information could be invaluable for the design of vaccines and immune-modulating drugs.Read moreRead less
Inhibiting pathological signalling in haematopoietic disease. Certain leukaemias and other blood diseases are caused by the mutation of one particular molecule, called Janus Kinase (JAK), inside our bodies. This project aims to understand the biochemical details of these diseases by studying this mutated molecule in detail. The project will aim to provide the information for developing effective therapeutics against these diseases.
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less
Mechanisms Of Regulation Of Ribosome Biogenesis And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
The PI3K/AKT signalling pathway drives many cancers and until recently was thought to do so by preventing cancer cell death. We have shown this pathway also regulates the synthesis of ribosomes, the cellular “factories” that make protein and by interfering with PI3K/AKT regulated ribosome synthesis, can kill cancer cells. We aim to establish the mechanisms underlying this regulation of ribosome synthesis and to test the hypothesis that ribosome biogenesis is a novel target for cancer treatment.