Examining The Contribution Of Mutant DNMT3a In The Development And Sustained Growth Of Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$820,880.00
Summary
Experimental models of Acute Myeloid Leukaemia (AML) have been valuable tools for studying this cancer. Recent analysis of human cancer genomes identified novel mutated gene products implicated in AML. To study the involvement of these genes in the development and sustained growth of AML, we will generate new experimental models that express the mutated forms of these newly described genes. These studies will assist in the development of improved treatments for patients with AML.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
The Mechanisms Of Epithelial Cell Survival That Govern Thymus Function
Funder
National Health and Medical Research Council
Funding Amount
$620,967.00
Summary
The thymus is an organ dedicated to the production of crucial immune cells, called T lymphocytes. Cancer treatments, such as radiation or chemotherapy, destroy thymic function and impair immune recovery in patients. We aim to uncover molecular processes that govern the life and death decisions of cells in the thymus. Our goal is to then use this information to develop treatments to protect this critical organ from damage and improve immune recovery following radiation or chemotherapy.
Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
Development Of Small Molecule Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$621,558.00
Summary
Cancers rely on the deregulation of key cellular pathways. Along with biological and genetic tools, small molecules are powerful probes to understand these mechanisms. During the course of this research program, we will develop new and drug-like molecules that reinstate the cell death process to combat malignancies. This research will bring important advances for potential chemotherapies and create probes to better understand the biology of programmed cell death processes.
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.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
The balance between cellular survival and death must be tightly regulated. Cells respond to viral infection by self-destructing, thus limiting viral spread to other cells. Viruses have evolved ways to subvert this defensive cell suicide. This project will define and characterise viral factors that maintain host cell survival during infection. These may be targets for the development of new anti-viral therapies and vaccines.
Controlling Life And Death Of Dendritic Cell Subsets For Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$639,577.00
Summary
Dendritic cells are pivotal in orchestrating immune responses; for example, they can turn immune cells into assassins to kill virus infections. Their function is so diverse that different dendritic cells do different jobs. There are many genes that control life and death of cells but those that are important for each specialised dendritic cell have not been comprehensively studied. Drugs that affect the proteins made by such genes selectively may be a new way of controlling immune responses.
The Cell Death Mechanisms That Control Regulatory T Cell Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$583,782.00
Summary
A central question in immunology is how to prevent destructive immune responses (e.g. autoimmune disease) and initiate productive immune responses (e.g. against cancer). A major breakthrough in this area was the discovery of special immune cells, called a Regulatory T Cells. We propose to discover the genes that determine whether these cells live and die. We will use this information to control appropriate numbers and function of Regulatory T Cells to modify the immune system.