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.
Astrocyte Regulation Of Ammonia And Glutamate In Neonatal Hypoxia-Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$523,804.00
Summary
Lack of oxygen is a common problem for newborn infants, ocurring during events such as a difficult labour, and can lead to brain damage. We have discovered that a protein in the brain which normally removes ammonia (a toxic product of metabolism) is rapidly lost after a brief period of low oxygen. We propose that a build up of ammonia in the brain may be a key damaging event in hypoxia-related brain injury, and that it will be ameniable to therapeutic intervention.
PROTECTING THE PRETERM FETAL BRAIN FROM HYPOXIA AND INFECTION: A HEALTHY START TO LIFE.
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. In recent years it has become evident that infections in the mother may be linked to both premature bi ....Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. In recent years it has become evident that infections in the mother may be linked to both premature birth and brain damage. It has been proposed that certain chemicals (cytokines), which are released during an infection, can cross the placenta to the fetus causing inflammatory changes that lead to brain damage. We have shown that an inflammatory inducing chemical (bacterial endotoxin) administered to immature fetal sheep induces brain damage similar to that seen in cerebral palsy. This provides an excellent model for testing agents that are known to block the action of cytokines and other markers of inflammation; currently there is no effective strategy for the treatment or prevention of hypoxia and inflammatory induced injury of the brain partly due to our ignorance about how and when the damage is occurring. We will test the effects of two chemicals; N-acetyl cysteine, which is known to block the generation of inflammatory cytokines, and the naturally occurring glycoprotein erythropoietin, which prevents death of neurons (apoptosis). We hope that by blocking these pathways we may be able to prevent brain injury from occurring when the immature fetus is exposed to an infection during gestation. We expect that this project will provide important novel information that helps us to understand how infection in the mother can cause brain injury in the fetus and provide a new approach for strategies to prevent or treat brain injury.Read moreRead less
Single-chain Antibodies For Directed Stem Cell Homing And Targeting Of Effector Cells In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$596,677.00
Summary
Regenerative cellular therapy e.g. with adult stem cells is a promising novel medical therapy. However, until now there is no reliable method to direct cells to areas where they are needed. We aim to develop a biotechnological approach based on genetically tailored antibody molecules that will allow cell targeting. As a pilot project we will test whether this approach improves lipid deposition and hardening of arteries.
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.