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.
Coordination Of Withdrawal From The Cell Cycle By Transcriptional Repression
Funder
National Health and Medical Research Council
Funding Amount
$271,650.00
Summary
Cancer is characterised by changes in several fundamental cellular processes including the failure of the cancer cells to stop growing in response to the body's normal stop signals.. When cells normally stop growing there is profound changes in the activity of many genes. This proposal aims to investigate how these changes in gene activity are brought about. We propose that a recently discovered family of genes called SWI-SNF work with two other families of genes (the Mad-family and Rb-family) t ....Cancer is characterised by changes in several fundamental cellular processes including the failure of the cancer cells to stop growing in response to the body's normal stop signals.. When cells normally stop growing there is profound changes in the activity of many genes. This proposal aims to investigate how these changes in gene activity are brought about. We propose that a recently discovered family of genes called SWI-SNF work with two other families of genes (the Mad-family and Rb-family) to bring about the cessation of cell growth. If our proposal is proven it will open new avenues to evaluate the growth properties of human cancers and may lead to novel strategies to inhibit cell growth.Read moreRead less
Tyrosine Kinases And Phosphatases In Cell Cycle Checkpoint Responses
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. ....In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.Read moreRead less
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.
Neogenin Regulates Progenitor Division And Interneuron Migration In The Developing Forebrain
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
In humans, mutations in genes controlling the production of new neurons in the embryonic brain result in severe disruption of the adult cortex. This project tests the hypothesis that one cell surface molecule, Neogenin, regulates the birth of new neurons and their subsequent travels through the developing brain to form the neocortex. The outcome of these studies will provide fundamental insights into the aberrant processes that underlie human mental retardation, epilepsy, dyslexia and autism.
Cell Cycle Regulation, Haemopoietic Stem Cells And Myeloproliferation.
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
My research has focused on understanding how the process of cell division can result in different outcomes for adult blood stem cells. I am interested in determining the role of bone and blood vessels in the regulation of blood stem cells and in the development of blood diseases (myeloprolifertive disease). I will also determine the effects of changing the cell cycle with drugs to improve transplantation of blood stem cells.
Cell Division And The Regulation Of Immunoglobulin Switch Recombination At The Molecular Level
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
The B lymphocyte is an important cell in the immune response as it generates protective antibody against invading pathogens. The effectiveness of an antibody response partly depends on the type of antibody made (there are eight different types). This attribute alters as the immune response progresses in a poorly understood and highly complex way. However, our recent studies have revealed a simple underlying order that can be dissected using new methods. The key to the underlying simplicity is a ....The B lymphocyte is an important cell in the immune response as it generates protective antibody against invading pathogens. The effectiveness of an antibody response partly depends on the type of antibody made (there are eight different types). This attribute alters as the immune response progresses in a poorly understood and highly complex way. However, our recent studies have revealed a simple underlying order that can be dissected using new methods. The key to the underlying simplicity is a cell division clock used to relate and promote cell changes. Here we intend to apply this new concept and the new methods to dissecting the molecular events associated with linking division to the changing properties of antibody selection. Our aim is to accurately model the process of changing antibody types at both the molecular and whole tissue levels. These studies will give us new insights into how the immune response may be directed to make the most appropriate (effective) response during infection and vaccination.Read moreRead less
ISG60, A Novel Interferon-induced Protein: Cell Growth Inhibitory Actions
Funder
National Health and Medical Research Council
Funding Amount
$197,030.00
Summary
The interferons are signaling molecules produced by cells as part of an early warning sytsem to alert nearby tissue cells and immune cells to defend themselves against an impending viral attack or aberrant growth of cells. We have discovered ISG60, a new member of a group of proteins called the ISG54 family. The production of this family of proteins is turned on in all cells responding to the interferons. Exactly what the members of the protein family do within cells remains to be established. H ....The interferons are signaling molecules produced by cells as part of an early warning sytsem to alert nearby tissue cells and immune cells to defend themselves against an impending viral attack or aberrant growth of cells. We have discovered ISG60, a new member of a group of proteins called the ISG54 family. The production of this family of proteins is turned on in all cells responding to the interferons. Exactly what the members of the protein family do within cells remains to be established. However, by preparing cells which produce the ISG60 protein, we have found that it severely affects their growth, slowing the growth rate down and making the cells divide abnormally to become large, containing many nuclei and others dying. We propose that ISG60 binds to the structures involved in cell division and we have preliminary evidence that ISG60 interacts with an important protein involved in cell regulation, the retinoblastoma protein (pRb). The aim of this project is to more fully understand the role of ISG60 in cells. In particular, we aim to determine if ISG60 interacts with other important proteins inside cells. We shall explore the relationship of ISG60 function inside cells in greater detail as it should provide new insight into ways in which cell growth is regulated. This study will also provide insight into how the slowing of cell growth makes the cells less suitable for viral infection and reproduction, as well as providing new approaches for preventing the growth of cancer cells.Read moreRead less