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.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
Sex Chromosome Instability In Disorders Of Development
Funder
National Health and Medical Research Council
Funding Amount
$627,633.00
Summary
Chromosomes must be copied and distributed faultlessly into the newly dividing cells for normal development to occur. Factors that affect this process are often associated with health problems such as birth disorders, cancer, premature aging and infertility. This project plans to identify genetic factors that compromise the faithful transmission of chromosomes from cell to cell. Results gained from this project will greatly assist in the diagnosis of chromosome-related disorders.
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.
Chemical And Structural Biology Validation Of Lamin B1 As A New Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$638,272.00
Summary
The validation of new anti-cancer targets is critical for the development of new therapies. We have discovered a small molecule that disrupt the function Lamin B1 during cell division and decreases tumour growth significantly in vivo. With this research proposal, we will investigate the role that Lamin B1 exerts during cell division and why interfering with this protein has such a profound impact on cancer cells.
Developing Cancer Therapies That Target Chromosomal Instability
Funder
National Health and Medical Research Council
Funding Amount
$644,126.00
Summary
A significant reason why late-stage cancers are hard to treat with drugs is because the tumour cells show genetic variability, always producing new variants that sooner or later get around the drugs. We intend to combat this by targeting the ability of cancer cells to vary genetically - we are discovering ways to specifically kill genetically unstable cells. This prevents the cancer from developing drug resistance as well as having less side effects on the patient's normal cells.
Endocytosis And Asymmetric Cell Division In Leukemia.
Funder
National Health and Medical Research Council
Funding Amount
$548,258.00
Summary
Self-renewal allows normal haematopoeitic stem cells to constantly replenish the blood system. Conversely, leukemia stem cells use self-renewal to propagate the disease, and utilise the quiescence phase to evade treatment eradication. We identified that the endocytic gene, Ap2a2 enhances haematopoeitic stem cell self-renewal. Through Ap2a2, we are now investigating the role of endocytosis and self-renewal in leukemia and ex vivo expansion of human haematopoietic stem cells.
Targeting Nucleic Acid Synthesis And Cell Division In Gram-negative Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$966,800.00
Summary
Some bacteria like Acinetobacter species cause infections in hospitals that are difficult to treat because they have acquired resistance to most antibiotics. This project will combine the complementary expertise of five research groups to develop knowledge of, and how to block, three essential processes in these worrying pathogenic species: copying of DNA, RNA synthesis, and cell division. This promises to lead to development of new antibacterial therapies.
Chromosomes must be copied and distributed faultlessly into the newly dividing cells for normal development to occur. Factors that affect this process are often associated with health problems such as birth disorders, cancer, premature aging and infertility. This project plans to identify genetic factors that compromise the faithful transmission of chromosomes from cell to cell. Results gained from this project will greatly assist in the diagnosis of chromosome-related disorders.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.