To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that c ....To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that can kill tumour cells more effectively by directly triggering the normal death switch of the cell.Read moreRead less
Learning The Mechanisms Of Programmed Cell Death And Tumour Suppression To Develop Novel Cancer Therapies
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
Our bodies prevent the development of cancer through tumour suppressive processes, which also affect the outcome of cancer therapy. Programmed cell death (apoptosis) is one such process, and defects in apoptosis promote cancer development and impair the response of tumour cells to anti-cancer therapies. My laboratory uses molecular biology and cell biology approaches to investigate the mechanisms of cell death and tumour suppression, partnering with pharma to develop novel cancer therapies.
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.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
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.
Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained a ....Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained and if this balance is lost then disease may result. A reduced level of cell death may result in cancers while too many dying can contribute to degenerative diseases such as Alzheimer's disease and stroke. Currently many of these diseases do not have effective treatments. We will determine the three-dimensional structures of key proteins involved in programmed cell death and use this information to design drugs that can interfere with the molecular processes involved in signalling cell death. Such drugs may prove useful new therapies in a wide range of diseases caused by a breakdown in the biochemical paths to cell death.Read moreRead less
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.