Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Toward Effective Targeted Therapies For Acute Myeloid Leukaemia (AML)
Funder
National Health and Medical Research Council
Funding Amount
$551,345.00
Summary
Standard chemotherapy for acute myeloid leukaemia (AML) is highly toxic, and has not changed in over 40 years. We will conduct a world-first clinical trial incorporating ABT-199 (Venetoclax) to target BCL2 into the standard-of-care treatment for AML. A second initiative will explore the potential for small molecule inhibitors to simultaneously target both BCL2 and its related partner MCL1, to create a “chemotherapy-free” regimen for AML. These studies promise to herald a new era in AML therapy.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Unlocking Hidden Cancer Drivers Using Transcriptome Data
Funder
National Health and Medical Research Council
Funding Amount
$700,473.00
Summary
New sequencing technologies allow us to get an unbiased look at the molecular signalling in a tumour. However this information is very complex and need specialised methods in statistic and computation in order to make new discoveries. Here will will develop analysis methods to find novel transcriptional variants in cancer and then test them in the lab in order to understand if our discoveries are responsible for causing cancer.
Circulating Tumour DNA To Monitor Treatment Response And Resistance In Chronic Lymphocytic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$876,950.00
Summary
Many cancers shed small amounts of DNA (ctDNA) into the patient’s bloodstream and recent advances in genomic technologies now allow levels of ctDNA to be accurately measured in the blood. Changes in ctDNA levels have potential to be used as specific markers of disease progression and/or response to cancer therapy. This project will evaluate if ctDNA can be used to monitor treatment responses and individualise treatment decisions in patients with chronic lymphocytic leukaemia.
The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Motor Functioning In Young People With Attention Deficit Hyperactivity Disorder – Combined Type: A Three-dimensional Motion Analysis Study.
Funder
National Health and Medical Research Council
Funding Amount
$477,065.00
Summary
Attention deficit hyperactivity disorder –combined type (ADHD-CT) is a complex neuropsychiatric disorder with a progressively devastating impact on psychosocial development. The first objective of this study is to use 3D-motion analysis to ‘probe’ the underlying brain dysfunction which characterises ADHD-CT. The second objective of this study is to improve our understanding of the link between movement problems, and (a) injury proneness, and (b) social-communicative problems, in children with AD ....Attention deficit hyperactivity disorder –combined type (ADHD-CT) is a complex neuropsychiatric disorder with a progressively devastating impact on psychosocial development. The first objective of this study is to use 3D-motion analysis to ‘probe’ the underlying brain dysfunction which characterises ADHD-CT. The second objective of this study is to improve our understanding of the link between movement problems, and (a) injury proneness, and (b) social-communicative problems, in children with ADHD-CT.Read moreRead less
Improving The Neonatal Transition In Infants With A Congenital Diaphragmatic Hernia
Funder
National Health and Medical Research Council
Funding Amount
$551,644.00
Summary
Congenital diaphragmatic hernia is a common congenital abnormality and occurs when the diaphragm fails to separate the abdominal and thoracic compartments before birth. This prevents the lung from growing properly and so at birth, the lung is unable to take over the role of gas exchange without considerable assistance. As a result, these infants are at high risk of death or significant disability and this application is focused on improving care and reducing morbidity in these infants.