Structural Investigations Of The Bax And Bak Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$275,509.00
Summary
Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeut ....Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeutics.Read moreRead less
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.
Is The Tumour Suppressor Activity Of P53 Independent Of Its Transcriptional Role?
Funder
National Health and Medical Research Council
Funding Amount
$162,920.00
Summary
To become cancerous, a cell must avoid death. As such, cancer cells often contain defects in cell death pathways which render them resistant to pro-death stimuli, including many chemotherapeutic drugs. To design new and better cancer therapies, it is essential that we understand the critical molecular processes that control cell death. This will allow the development of more effective ways to either reset, or bypass, defects in cell death pathways which have contributed to cancer formation.
Understanding How BH3-only Proteins Initiate Apoptosis In Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$481,124.00
Summary
Failure to initiate cell death is a hallmark in the development of the majority of cancers and killing all tumour cells is essential for effective cancer treatment. A group of proteins termed the BH3-only proteins normally sense cell stress to trigger cell death. Their dysregulation contributes to cancer and failure to respond to chemotherapy. Understanding how these proteins function to induce cell death will allow the design of drugs that mimic this activity for improved cancer therapy.
Mechanisms Of Mcl-1- And Bcl-2-mediated Resistance To Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$439,796.00
Summary
Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TR ....Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TRAIL).Read moreRead less
Mechanisms Regulating Mitochondrial Outer Membrane Permeabilisation During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$306,562.00
Summary
Apoptosis is a form of cell suicide that is vital in human development and health by removing damaged or unwanted cells in a regulated manner. Disturbances in this pathway are known to be the cause of cancers and other diseases. This research will investigate how the pivotal step in cell death, termed mitochondrial outer membrane permeabilisation (MOMP) is regulated.
Defining The Stage Specific Requirements For Bcl-2 Family Members In The Development And Maintenance Of B Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Both vaccinations and pathogenic infections provoke an immune response. Our immune system ñmemorizesî this response, enabling a faster and stronger reaction upon re-encounter. This memory requires specialized cells of the immune system, some of which secrete antibodies and some of which patrol the body. Remarkably, these cells can live for decades in humans and provide immunity. In this project we will study the roles of specific proteins regulating the generation and survival of memory cells.
Investigating Mitochondrial Outer Membrane Permeabilization During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$88,065.00
Summary
Cancer cells often contain defects which prevent their death. To kill cancer cells we must either reset or bypass these defects. Release of cytochrome c from mitochondria is a critical event in cell death and proteins that block this event render cells resistant to many cancer therapies. My research will determine how cytochrome c release occurs, how this event is regulated and how to kill cancer cells in which cytochrome c release is blocked.
The Bcl-2 Life/death Switch - Why Do Some Bcl-2 Proteins Kill Cells Whilst Others Promote Their Survival?
Funder
National Health and Medical Research Council
Funding Amount
$375,510.00
Summary
The cells of all animals possess the ability to commit suicide. When this natural process of cell death is dysfunctional, diseases such as cancer arise. Our aim is to understand the molecular mechanisms that underlie this process by providing atomic resolution snapshots of key components of the cell death machinery. By understanding the fine details of cell death regulation we can develop new drugs that target and kill rogue cells such as those found in tumours.