Using Mouse Models To Decipher The Function Of Caspase-2 In Limiting Aneuploidy Tolerance And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$871,162.00
Summary
Aneuploidy or abnormal chromosome number is a feature of cancer cells. The extent of aneuploidy is often predictive of prognosis and the effectiveness of cancer treatment. We discovered that a tumour suppressing protein, caspase-2, is important for deleting aneuploid cells that may otherwise become cancerous. In this project we will use cancer models to decipher how caspase-2 safeguards against aneuploidy and cancer to better understand how cancer cells can survive and be targeted for treatment.
Antioxidant Enzymes Counter Reactive Oxygen Species From Steroidogenic Cytochrome P450 Enzymes In The Ovary To Limit Aneuploidy Of Embryos
Funder
National Health and Medical Research Council
Funding Amount
$536,978.00
Summary
Many birth defects are due to damage sustained by the eggs before ovulation. Aging allows more damage, hence the advice to have babies earlier in life. However, we believe we have identified a source of damage that happens during late development of the follicle in the weeks before ovulation. Proving this will enable us define when an egg is most at risk of damage and to devise strategies to lower the risk.
The Role Of Centromere Defects In Cancer Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
When cells divide, their DNA must be copied and distributed faultlessly into the new cells. Defects in the factors that control this process will result in serious health problems including cancer. The objective of this project is to identify what these factors are and study how they contribute to cancer. Results gained from this project are expected to significantly increase our understanding of how cancer cells control the replication of their DNA and therefore their own fate.
Molecular Basis For Female Age-associated Decline In Oocyte Quality And Fertility
Funder
National Health and Medical Research Council
Funding Amount
$71,792.00
Summary
Many women cannot have children because of suboptimal egg quality, often due to ageing. In order for novel strategies to be developed for improving egg quality, it will first be important to understand how key factors in eggs are regulated. This project will use state-of-the-art techniques to interrogate a pivotal pathway we have discovered in eggs that could be responsible for age-related decline and could hold the key to new approaches for rejuvenating eggs.
Targeting Chromosomal Instability By Metabolic Stress
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
The most intractable cancers gain and lose DNA as they grow, making them highly variable and drug resistant. We have found that mild disruptions to their use of energy can specifically kill cells with this kind of genetic instability. In this project we will characterize the mechanism by which metabolic stress affects cell division and the survival of genetically unstable cells. Our objective is to find treatments with no effects on normal cells that eliminate unstably dividing cancer cells.
Investigating The Role Of Novel Heterochromatin And Centromere Proteins In Chromosome Segregation
Funder
National Health and Medical Research Council
Funding Amount
$522,896.00
Summary
The equal division of genetic material during cell division is essential so that genetic material is not lost or gained. This process is controlled by a complex array of proteins that replicate the genome, maintain its structural integrity, and equally distribute one copy to each daughter cell. This research aims to study the functions of newly identified proteins required for this process in a single cell yeast model-system and in human and mouse cells.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
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.