Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
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.
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.
Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
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.
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
Determining recurrence risk in breast cancer is crucial, as more than half of all recurrences occur after 5 years. However, optimal management of breast cancer is hampered by the challenges in finding rational preventative and predictive targets. Our vision is to find targets responsible for progenitor cell expansion, as candidates for prevention, and to find markers of relapse, to predict early versus late responders to therapy.
Understanding The Biological Regulation Of MLKL And Its Role In Necroptotic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$656,979.00
Summary
Cell death is a normal process that permits the growth and defence of our vital tissues. One kind of cell death, necroptosis, is characterized by the swelling and bursting of cells. When cells ‘explode’ in this uncontrolled way they provoke an inflammatory response. This may be a factor behind illnesses ranging from colitis to cardiovascular disease. Understanding necroptotic cell death may pave the way for new therapies for those that suffer from these devastating conditions.