The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.
UNDERSTANDING FOCAL ADHESION DYNAMICS IN CELL MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$268,944.00
Summary
Metastatic (secondary) cancers are a frequent cause of patient mortality. Central to the development of metastasis is cell motility-movement. A key component of cell movement is the way that cells bind and release the extra-cellular matrix as they move. By understanding how the dynamics of cell interaction with the matrix are regulated, we will identify molecules that are critical to the development of metastatic cancer and thus novel targets for inhibition of metastasis.
Regulation Of Cell Proliferation By The Actin Cytoskeleton
Funder
National Health and Medical Research Council
Funding Amount
$607,795.00
Summary
The architecture of cells defines both their shape and function. It has been known for a long time that cell architecture controls the growth of cells and in particular their capacity to proliferate. We have identified part of the architectural system which controls this process. In this project we will establish how this works and its role in the body. This research will test whether this part of the cell�s architecture is a suitable drug target for the treatment of disorders in cell growth.
Induction Of Senescence In Cells That Use The Alternative Lengthening Of Telomeres (ALT) Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$474,048.00
Summary
Approximately 10-15% of all cancers depend on Alternative Lengthening of Telomeres (ALT) for their continuing growth. A key aspect of many successful cancer treatments is that they force cancer cells to undergo a form of permanent growth arrest called senescence. In this study we will investigate characteristics of ALT-positive cancer cells that may make them especially vulnerable to senescence. This may be exploited in the future as a therapeutic strategy for cancers that depend on ALT.
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
The Role Of The M6P-IGF-II Receptor In Regulating Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
We will investigate if a cell surface protein that suppresses the growth of breast cancer cells is also able to reduce the cancer spreading to other organs. The part of the molecule required for this effect will be identified so that smaller forms of the protein can be tested to inhibit tumour spread. Genes and proteins altered by the presence of this protein in breast cancer cells will be examined to determine how the protein suppresses tumours and to identify novel tumour markers.
The Molecular Mechanisms Of Abscission To Complete Cytokinesis
Funder
National Health and Medical Research Council
Funding Amount
$736,337.00
Summary
Cytokinesis is the final stage of cell division that produces two daughter cells. Incorrect localisation and modification of proteins that regulate this process cause cell division errors potentially leading to cancer. This project will characterise how key cytokinesis proteins function co-operatively to complete cytokinesis. This research will increase our understanding of the cell division errors that contribute to cancer development, ultimately identifying new targets for cancer therapy.
Using Drosophila To Define An Epithelial Cancer Stem Cell
Funder
National Health and Medical Research Council
Funding Amount
$552,988.00
Summary
Cancer is a complex disease that involves the mis-regulation of genes and aberrant cell-cell communication . To help gain a better understanding of these processes it is possible to examine simpler systems. This proposal uses a unique cancer model in flies to understand how a change in cell fate can endow cells with the ability to continue dividing and invading surrounding tissues, thus driving cancer development.
A Single Nucleotide Resolution Map Of A Cancer Associated Neochromosome
Funder
National Health and Medical Research Council
Funding Amount
$567,350.00
Summary
Neochromosomes (NCs) are large chromosomes which are not usually found in a normal cell. Well differentiated liposarcoma (WDLPS) is a tumour which is almost universally associated with the presence of NCs. We are using the approach of purifying the NC from a series of WDLPS cell lines, and using new techniques to derive the DNA sequence of the neochromosome. We will use this information to identify the genetic factors on the NC which are involved in the initiation or progression of WDLPS.
The overall incidence of primary brain tumours in the Western world is 10 per 100,000 people. Unlike many other tumours, these occur in patients of all ages and comprise the second most common tumour type among children and young adults. Most brain tumours remain incurable. We are using our expertise in the field of neural stem cell research to characterise tumour cells responsible for resistance to treatment, with the final goal of identifying new targets for therapeutic intervention.