Regulated Shuttling Of Beta-catenin And IQGAP1 Between Nucleus And Plasma Membrane In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,703.00
Summary
Inherited gene mutations that cause colon cancer kill 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by age 75. Activation of the beta-catenin protein is a critical switch in the path to colon cancer. We discovered that beta-catenin, and another protein it interacts with called IQGAP1, move between different cellular compartments. We plan to study this process in more detail, as it relates to how beta-catenin works and to understanding its role in cancer.
Targeting Of The APC Tumour Suppressor To Mitochondria: Implications For APC Regulation And Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$390,116.00
Summary
Inherited mutations in the APC gene cause colon cancer, and kills 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by the age of 75. APC mutations change cells in different ways, triggering the cancer process. We have discovered a new pathway, involving altered movement of APC to mitochondria in tumour cells. This study will investigate how this cancerous change may help our understanding of colon cancer progression.
Escape From BRAF-induced Human Melanocyte Senescence In The Genesis Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$601,776.00
Summary
Melanoma is the most lethal form of skin cancer and activation of the MAPK growth pathway is a crucial step in the initiation of this cancer, but alone is insufficient, as most melanocytes with active MAPK exist in a growth arrested state. The mechanisms responsible for arresting melanocytes in the presence of active MAPK will be investigated. This project will discover why some melanocytes develop into melanomas whereas most do not.
Insertion and assembly of proteins and lipids into biological membranes. We propose a multi-disciplinary approach to this fundamental biological problem and have established collaborations with experts in the USA, UK and Austria. Benefits from this research program fall into two discrete types. Firstly, detailed knowledge of the mechanism what is now a poorly understood biological process of cellular membrane assembly, with the prospects for using the knowledge for intervention into diseases suc ....Insertion and assembly of proteins and lipids into biological membranes. We propose a multi-disciplinary approach to this fundamental biological problem and have established collaborations with experts in the USA, UK and Austria. Benefits from this research program fall into two discrete types. Firstly, detailed knowledge of the mechanism what is now a poorly understood biological process of cellular membrane assembly, with the prospects for using the knowledge for intervention into diseases such as cancer. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia.Read moreRead less
Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which in ....Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which involves the cleavage of the cell membrane to produce two daughter cells. Here, we aim to characterise the mechanism(s) of CMAP function and to identify and characterise CMAP binding proteins to further understand the mechanisms involved in the final stages of cell division to maintain genomic stability.Read moreRead less
Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by ....Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by FOXO proteins. Although very basic in nature, these projects will identify how FOXO proteins regulate muscle cell building and wasting and, therefore, present a potential therapeutic target for muscle wasting diseases, making this project highly significant.Read moreRead less
Regulation and function of a novel protein tyrosine phosphatase. A cell's ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular processes that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-depe ....Regulation and function of a novel protein tyrosine phosphatase. A cell's ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular processes that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-dependent signalling. We have identified a novel human protein tyrosine phosphatase and we aim to characterise its regulation and biological function.Read moreRead less
Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less