A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.
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.
Defining The Role Of Glycosylation In Basement Membrane Failure During Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$824,664.00
Summary
This project aims to utilize mutations within the zebrafish fkrp gene to understand the pathogenic basis of the human diseases associated with mutation of this gene which results in a spectrum of muscular dystrophies. By generating models of alleles that represent the range of phenotypes seen in humans we will have a directly translatable model system to human pathology.
Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
Modulation Of MicroRNA Activity In The Testis: A New Paradigm For Male Fertility?
Funder
National Health and Medical Research Council
Funding Amount
$419,170.00
Summary
Sperm production in the testis is driven by the reproductive hormones, follicle-stimulating hormone (FSH) and testosterone. In this grant, we will investigate how a new class of molecules, called microRNAs, act to transmit the signals from FSH and testosterone to the cellular machinery of the testis, particularly at junctions between cells. This information has the potential to impact on our understanding of the causes of male infertility.
Evaluation Of Molecular Mechanisms Driving Metastasis Using Integrated Intravital Imaging
Funder
National Health and Medical Research Council
Funding Amount
$885,271.00
Summary
Metastasis is the leading cause of cancer-associated death. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and 3-dimensional model systems that mimic the disease, we will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Haematopoietic Stem Cell Glycome Regulates Outcome Of Niche Interactions
Funder
National Health and Medical Research Council
Funding Amount
$913,729.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a factor in the BM which when blocked, puts normal HSC to sleep helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. This factor also helps leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Mechanisms By Which Endothelial Selectins Regulate Normal And Malignant Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$708,742.00
Summary
Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a molecule in the BM which when increased during inflammation, awakens normal HSPC. We previously showed this molecule also helps leukaemia and other cancer stem cells resist chemotherapy. We have now identified the mechanism why. These proposed studies open new therapeutic avenues to sensitise cancer stem cells to therapy enabling long-term cure.
Glioblastomas are the most common and lethal brain tumours and 5 years after diagnosis only 20% of patients diagnosed with a glioblastoma will be alive. The poor survival rate is due to the ability of these tumours to extensively penetrate into the surrounding healthy brain tissue making complete surgical removal very difficult. Our research aims to discover how the glioblastoma cells can penetrate neighbouring brain tissue.