Defining The Molecular Events That Initiate The Genesis Of Lymphatic Vessels.
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including lymphoedema, cancer and inflammatory diseases. The focus of this application is to determine the molecular events that initiate the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
Dissecting The Embryonic Blood-endothelial Regulatory Code And Investigating Its Role In Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$646,389.00
Summary
Cancer initiating cells acquire stem cell characteristics and multiply within a supportive environment that helps maintain and propagate malignant cells. Identifying the normal hierarchy of gene control within blood stem cells and designing therapies that target cancer cells is the ultimate goal of this body of work.
Defining The Role Of VEGF And Vascular Formation In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$636,417.00
Summary
Aberrant neural crest cell development gives rise to common congenital malformations such as cleft lip and/or palate and cardiac outflow tract defects that effect over 1% of all births. As the aetiology of these disorders are largely unknown it is critical to understand the cell and molecular mechanisms coordinating NCC development such that alternative therapies may be devised to target the underlying pathological defects and to provide definitive diagnostic / prognostic tools.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
Determining recurrence risk in breast cancer is crucial, as more than half of all recurrences occur after 5 years. However, optimal management of breast cancer is hampered by the challenges in finding rational preventative and predictive targets. Our vision is to find targets responsible for progenitor cell expansion, as candidates for prevention, and to find markers of relapse, to predict early versus late responders to therapy.
Understanding The Biological Regulation Of MLKL And Its Role In Necroptotic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$656,979.00
Summary
Cell death is a normal process that permits the growth and defence of our vital tissues. One kind of cell death, necroptosis, is characterized by the swelling and bursting of cells. When cells ‘explode’ in this uncontrolled way they provoke an inflammatory response. This may be a factor behind illnesses ranging from colitis to cardiovascular disease. Understanding necroptotic cell death may pave the way for new therapies for those that suffer from these devastating conditions.
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 different transcription factors in the Hippo pathway operate to control tissue growth. 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 For Regulation Of Myc Transcription And Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$645,347.00
Summary
We aim to use the animal model system, the vinegar fly, to investigate mechanism for cancer initiation. The fly has been studied for over 90 years and has proved an excellent genetic model for understanding the complex processes leading to abnormal cell growth, which is associated with the early stages of human cancer. The high level of conservation between fly genes and human cancer genes means these studies will provide novel insights into the genetic mechanisms underlying tumour formation.