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.
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.
Investigating The Apoptotic Function Of Bak And Bax
Funder
National Health and Medical Research Council
Funding Amount
$476,271.00
Summary
Proper regulation of how and when cells die is crucial for the development and maintenance of a healthy body and mind. We shall investigate the key proteins that are ultimately responsible for killing a cell with the long term view to identify ways to target these proteins for the treatment of conditions including neurodegenerative and cardiovascular diseases.
Role Of Bak And Bax Membrane Anchors In Targeting And Apoptotic Pore Formation.
Funder
National Health and Medical Research Council
Funding Amount
$352,319.00
Summary
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak and Bax proteins are members of the Bcl-2 family of apoptosis regulators, and play a pivotal role in mediating cell death. By defining how these proteins form a pore in mitochondria, the point of no return in cell death, will help the development of novel anti-cancer agents that target the Bcl-2 family in general, and Bak and Bax in particular.
Deciphering Activation Of The Apoptotic Cell Death Program
Funder
National Health and Medical Research Council
Funding Amount
$577,109.00
Summary
Apoptosis is the cell death mechanism by which unwanted, damaged or excess cells are removed from the body. It is critical for normal development and immune system function, and is deregulated in a number of diseases including cancer, neurodegeneration and autoimmunity. We shall determine how apoptosis is controlled by a family of proteins called the Bcl-2 family, thereby providing insight for the development of novel therapies.
Alternative Mechanisms To Initiate Apoptotic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Cell death is essential for our well being. As insufficient cell deaths can lead to cancers, promoting cell killing is a promising new avenue for treating this disease. However, current approaches are not fully optimal because we do not completely understand how the switch for cell death is flipped on. Our project seeks to answer this important question and we anticipate that a better understanding of this basic process will enable improved treatment for diseases such as cancer.