Molecular Mechanisms Of Mitotic Progression And The Anti-cancer Properties Of Anti-mitotic Agents
Funder
National Health and Medical Research Council
Funding Amount
$466,492.00
Summary
Mitosis is the final stage of the cell division cycle 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 mitotic proteins co-operatively function to complete this process. This research will increase our understanding of the cell division errors that contribute to cancer development, ultimately identifying new targets for cancer therapy.
Defining The Role Of Microphthalmia-associated Transcription Factor (MITF) In Melanoma Heterogeneity By Real-time Cell Cycle Imaging
Funder
National Health and Medical Research Council
Funding Amount
$613,705.00
Summary
Metastatic melanoma is highly therapy-resistant. Modern targeted therapy is promising but suffers from rapid onset of drug resistance. Tumours consist of zones of fast growing cells next to zones of dormant cells. This tumour heterogeneity is one of the reasons for cancer drug resistance, as cells in different growth states respond differently to drugs. By understanding the causes of tumour heterogeneity we will set the basis for innovative clinical approaches against this devastating disease.
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.
Identifying The Mechanism Of The G2 Phase UV Checkpoint And Repair Response Commonly Defective In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$569,656.00
Summary
The UV component of sunlight is the major environmental factor driving the development of melanoma. UV radiation can directly mutate genes resulting in their inability to perform normal functions which may contribute to cancer. Despite the high number of mutations directly attributable to UV radiation, the mechanisms known to repair these mutations are generally normal in melanoma. This research will investigate a repair mechanism we have identified that is commonly defective in melanomas.
Synthetic Lethality Screen Targeting A Defective Checkpoint In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$552,121.00
Summary
All cancers have defects in the mechanisms that regulate normal cell growth and division. These defects provide a growth advantage for the cancer, but can also be an Achilles Heel. In this project we will investigate targeting a defective control mechanism we found in a high proportion of melanomas. We will identify genes that when inhibited combine with the defective control to specifically kill tumour cells with this defect. Normal tissue is protected by its intact regulatory mechanism.
Real-time Imaging Of Cell Cycle Progression In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$526,911.00
Summary
Melanoma is the most aggressive skin cancer and is highly therapy resistant, reasons of which are poorly understood. Here we hypothesise that differences in the growth capacity of melanoma cells in different tumour regions contribute to therapy resistance. We will use a novel microscopic system that allows us to visualise division of individual melanoma cells in intact tumours in real time. Using this system, we will test the effects of targeted therapies on melanoma cell growth and survival.