Therapeutic Targeting Of Ribosome Biogenesis In Cancer And Ribosomopathies
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
My fellowship application will build on my international leadership in understanding growth control in human disease. My vision is to uncover the molecular mechanisms governing the loss of normal control of the synthesis of the molecular machines, termed ribosomes, that are responsible for synthesising all cell proteins. I will translate these findings into new paradigms to treat patients suffering from diseases such as cancer and ribosomopathies, that are associated with ribosome dysfunction.
Restoration Of P53 Activity In Tumours: A New Approach Involving The P53 Coactivator ANKRD11.
Funder
National Health and Medical Research Council
Funding Amount
$465,990.00
Summary
p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer functio ....p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer function in mutant p53 leading to tumour regression.Read moreRead less
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.
I am a cancer biologist determining the mechanisms controlling growth and proliferation of cancer cells and use transgenic models of malignancy and genetic approaches to identify new therapies for targeting growth control in the treatment of cancer.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
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.
RNA Polymerase I: A Novel Target In The Treatment Of MYC Driven Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is dysregulated during cancer leading to the hypothesis that it may be causative in the malignant process. This application will test this hypothesis using novel inhibitors or ribosome biogenesis in a mouse genetic model termed E�-MYC that faithfully that replicates human B-cell lymphoma. These studies will uncover novel mechanisms in malignant transformation and identify new therapeutics in the treatment of human cancer.
Role Of Chromatid Cohesion In Colon Biology And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$628,422.00
Summary
Rad21 is a gene, present in many species and essential for accurate chromosome separation and DNA damage repair. Based on its known function in different species, we predict that its� dysfunction fuels cancer progression by promoting genetic instability, which is commonly associated with human cancers. This study will use unique mouse mutant models to investigate the function of this potential cancer-causing gene in colon cancer.