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
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.
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.
Targeting To Mitochondria Of Tail-Anchored Proteins. Defining The Molecular Apparatus Of Targeting.
Funder
National Health and Medical Research Council
Funding Amount
$254,751.00
Summary
The cells of the body have an intricate and dynamic internal architecture, with the components (proteins, lipids, and nucleic acids) of the cell carefully arranged. It is widely viewed that just how each component finds its place in the cell, the cellular adressing system, is of critical importance. This was recognized this year by the award of the Nobel Prize in Medicine to Dr. Gunter Blobel for his work on the signals that direct different proteins to their correct destination. One such destin ....The cells of the body have an intricate and dynamic internal architecture, with the components (proteins, lipids, and nucleic acids) of the cell carefully arranged. It is widely viewed that just how each component finds its place in the cell, the cellular adressing system, is of critical importance. This was recognized this year by the award of the Nobel Prize in Medicine to Dr. Gunter Blobel for his work on the signals that direct different proteins to their correct destination. One such destination is the mitochnondria, the particles in the cell that produce chemical energy. The work in this proposal is designed to define precisely the molecular apparatus that targets a group of proteins to mitochondria. This group, proteins that are inserted into the mitochondria at one end of the protein, includes a variety of critical proteins, including those that determine the life or death of a cell. We will define both the address contained within those proteins, and the machinery on the mitochondria that recognizes that address, and ensures that those proteins will become part of the mitochondria. This research has two applications. By understanding the address, we will be able to decode the vast amount genomic data that is being produced, to predict exactly which proteins are delivered to mitochondria. Secondly, by understanding the targeting machinery, we may begin to design molecules that can inhibit its function, and thus manipulate the delivery of those proteins that affect cell life and death.Read moreRead less
Detailed images of protein molecules underpin our understanding of biological function and our attempts to find new medicines to counter biological malfunction. Proteins belonging to the so-called Bcl-2 family determine whether a cell lives or dies and, because failure to die on cue is a hallmark of many cancers, high resolution images of these molecules will reveal new targets for cancer therapies.
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.