Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
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.
Mechanisms For Regulation Of Myc Transcription And Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$645,347.00
Summary
We aim to use the animal model system, the vinegar fly, to investigate mechanism for cancer initiation. The fly has been studied for over 90 years and has proved an excellent genetic model for understanding the complex processes leading to abnormal cell growth, which is associated with the early stages of human cancer. The high level of conservation between fly genes and human cancer genes means these studies will provide novel insights into the genetic mechanisms underlying tumour formation.
The Role Of A New Class Of Chromatin Organising Hub
Funder
National Health and Medical Research Council
Funding Amount
$1,145,450.00
Summary
Within the cell nucleus, specific proteins weave DNA into structured loops that are vital for normal cell function. By studying the molecules involved, we have uncovered a ‘dock’ that controls this DNA architecture. We will define the components and function of this ‘dock’, and the resulting rapid cell death that occurs if it is disrupted. We will explore this cell death pathway thoroughly because we think it may help us to develop new cancer therapies.
Caspase 8 Apoptotic Signalling Induced By The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The death of cells of our body can be an active and purposeful process. Programmed death occurs in response to infection or as a defence against cancerous changes. If a virally infected cell can die prior to replication of the virus, this will control the infection. We have investigated cell death in response to DNA found in the cytoplasm of cells, which can be an indication of infection. The novel cell death pathway we are characterising is relevant to defence against infection and tumours.
Regulation Of Ribosomal Gene Transcription By C-MYC During Differentiation And Lymphomagenesis.
Funder
National Health and Medical Research Council
Funding Amount
$287,261.00
Summary
A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however ....A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however, is not well understood. We have identified a novel process to link a cancer causing gene c-MYC to the control of protein production in cells through regulation of rRNA synthesis. Our experiments will examine the hypothesis that c-MYC directly affects the production of rRNA . Finally we will test the link between the ability of c-MYC to cause malignant growth of cells and its role in increasing synthesis of rRNA. These findings may lay the basis for new treatments for disorders of regulated cell growth such as cancer.Read moreRead less
How The Bcl-2 Protein Family Controls Apoptosis And Impacts On Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
Impaired cell death (apoptosis) is now recognized as an important step towards cancer and a major barrier to effective therapy. The discoveries on apoptosis by Professor Jerry Adams and colleagues have galvanized the search for drugs that engage the cell’s apoptotic machinery as a new way to treat cancer. His proposed studies aim to clarify how apoptosis is controlled and how the control goes awry in cancer, and to determine how such drugs can be most effectively used to improve cancer treatment ....Impaired cell death (apoptosis) is now recognized as an important step towards cancer and a major barrier to effective therapy. The discoveries on apoptosis by Professor Jerry Adams and colleagues have galvanized the search for drugs that engage the cell’s apoptotic machinery as a new way to treat cancer. His proposed studies aim to clarify how apoptosis is controlled and how the control goes awry in cancer, and to determine how such drugs can be most effectively used to improve cancer treatment.Read moreRead less
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.
The Role Of The Polarity Protein, Par3, In Haematopoiesis And Leukaemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$589,777.00
Summary
Understanding the factors regulating blood production is critical to understanding how blood cancers occur and for the development of new therapies. Evidence is emerging of a vital role for the evolutionary conserved ‘polarity’ proteins in blood production and leukaemia This project will elucidate the role of the polarity protein, Par3, in normal and malignant blood cells, providing valuable insight into how Par3 regulates blood formation and the onset and severity of leukaemia.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.