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.
Promoting Intestinal Stem-cell Mediated Regeneration Following Damage: A Critical Role For Neuregulin 1
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Diseases, infections and pathologies are common clinical problems of the intestine in humans that can lead to loss of intestinal tissue. Individuals with these conditions can experience nutritional problems and severe cases result in death. Promoting regeneration of the damaged tissue is critical to re-establish intestinal function. In this study, we will examine the regenerative potential of a growth factor called Neuregulin1 in the intestine with the aim of facilitating tissue regeneration.
Small Molecule Apoptosis Inhibitors To Define The Bak Activating Switch
Funder
National Health and Medical Research Council
Funding Amount
$713,687.00
Summary
Tissue loss due to excessive apoptosis is a contributing factor to organ transplant failure and other diseases characterised by too much cell death. Using an innovative cell-based screening approach, we have identified a first in class series of molecules that potently block cell death driven by the apoptosis effector Bak. By unravelling the molecular target of our unique inhibitors and characterising their mode of action, we hope to uncover a new facet of Bax and Bak biology.
Investigating The Role Of Mutant P53 And MCL-1 In The Sustained Growth Of MYC Lymphomas And Strategies For Targeted Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,940.00
Summary
A large number of human cancers have abnormal expression of a protein called MYC, leading to rapid growth. We found that when another protein called MCL-1 was inactivated, the lymphomas regressed. Importantly, mutations in the tumour suppressor gene called p53 are frequently found in cancer cells and we noticed that this could reduce the dependency on MCL-1. We aim to investigate this further in this grant proposal, in part using a novel drug that targets MCL-1.
The Role Of The Pro-survival Bcl-2 Family Member A1 In The Development And Sustained Growth Of Lymphomas.
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
The death of cells, which is regulated by a complex interaction between cell survival and killer proteins, is an important mechanism to prevent cancer. In this proposal we aim to understand the function of one of the cell survival proteins in cancer development and maintenance. This will help to develop novel therapeutic drugs specifically targeting this cell survival protein, thereby eliminating specifically the cancer cells and minimizing collateral damage of healthy tissues.
Dual Targeting Of Myc And Apoptosis Pathways For Improved Blood Cancer Treatment Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$754,685.00
Summary
Cancer cells frequently possess defects in genes called MYC and BCL-2 that control their growth and survival. Our preliminary studies have shown that combining novel reagents that specifically target MYC plus BCL-2 leads to enhanced lymphoma cell killing. In the proposed research, we will further develop these reagents and evaluate their ability to treat blood cancer in mice. We expect our approach will provide new avenues for treating cancer patients that respond poorly to current treatments.
Microtubule Severing: A Role In Mammalian Oocyte And Embryo Viability?
Funder
National Health and Medical Research Council
Funding Amount
$620,251.00
Summary
In all cells, cell division is controlled by a microtubule based structure known as the spindle. Abnormal function of this spindle leads to loss and gain of chromosomes that in oocytes causes early embryo loss and in cells of the body it causes cancer and cell death. We will investigate a family of proteins that modify microtubules and explore the role they play in ensuring cell division happnens safely.
Examining The Contribution Of Mutant DNMT3a In The Development And Sustained Growth Of Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$820,880.00
Summary
Experimental models of Acute Myeloid Leukaemia (AML) have been valuable tools for studying this cancer. Recent analysis of human cancer genomes identified novel mutated gene products implicated in AML. To study the involvement of these genes in the development and sustained growth of AML, we will generate new experimental models that express the mutated forms of these newly described genes. These studies will assist in the development of improved treatments for patients with AML.
The Mechanism Of Cell Death In Response To Cytoplasmic DNA, And Its Role In Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$517,897.00
Summary
DNA in mammalian cells is in a structure known as the nucleus. Retroviruses such as HIV generate DNA outside the nucleus in the cytoplasm, and detection of DNA in the cytoplasm can lead to cell death, as a defence. All cells carry the remnants of ancient retroviruses in their nuclear DNA. These are normally inactive but may contribute to cancer when activated. This project investigates how normal cells die with cytoplasmic DNA, and whether a defect in this process promotes development of cancer.
Deciphering The Role Of Scribble In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$628,789.00
Summary
Scribble is a protein that controls the orientation and organization of all cells within our body. Mutations in the Scribble gene are found in many cancers and also in some patients with spina bifida, however how these mutations cause these diseases is not understood. Here we propose experiments that can be used to link Scribble mutations to specific cellular functions. This information will help us design new therapies to treat diseases driven by tissue disorganization such as cancer.