Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
The cells that produce and maintain our cartilage, known as chondrocytes, do so by sensing changes in the mechanical environment, but precisely how chondrocytes detect these changes is not known. We are investigating the role of ion channels that are opened in direct response to mechanical movements within the cartilage.This project plans to identify the specific molecules that are participating in this process and to determine if they are therapeutic targets for treatment of osteoarthritis
Transient Tissue ‘priming’ Via FAK Inhibition To Impair Pancreatic Cancer Progression And Improve Sensitivity To Gemcitabine/Abraxane
Funder
National Health and Medical Research Council
Funding Amount
$643,848.00
Summary
The success of cancer drugs is dependent on many factors including the properties of the tumour tissue. As a tumour grows it changes the tissue around it, and this affects response to treatment. Combining classical biology with engineering to generate 3D models that mimic tumours, along with cutting-edge imaging technology and mouse models, we will target FAK-controlled cancer cell pathways that sense tissue changes, together with already approved cancer drugs to improve patient outcome.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.
Biosensor Imaging In Preclinical Pancreatic Cancer Targeting: Taking Cancer Targeting To New Dimensions.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Using cutting-edge imaging technology and 3D models that mimic cancer, we can map areas of poor drug response within distinct 'stages' or regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug response in order to improve the encouraging anti-cancer profile of new or current drugs in pancreatic cancer.
Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the ....Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the-art cell biology and proteomic technologies, the project aims to investigate how molecular chaperones orchestrate these changes and in doing so, improve understanding of the fertilisation cascade and open up new contraceptive strategies.Read moreRead less
Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplo ....Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplored. This study extends our successful mutational analysis of cellulose synthesis in Arabidopsis and initiates the molecular analysis of organisms making cellulose with distinctive properties. It will significantly advance knowledge of cellulose biosynthesis and identify novel genes for fibre improvement.Read moreRead less
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less