Regulation Of Endosome Function By The AAA-ATPase Vps4
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signal ....Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signalling protein from one side of the membrane where signalling occurs to the other side where signalling cannot occur and where the signalling protein can be degraded. Interestingly, it has recently been discovered that some viruses (including the AIDS virus) use the same MVB sorting mechanisms to escape from infected cells. Instead of undergoing MVB sorting into an internal compartment and getting degraded, however, the virus is able to use the same mechanism to flip out of the cell. How MVB sorting occurs is not known, but the mechanism has been conserved through evolution and even microbes like yeast can perform MVB sorting of proteins. We are investigating a component of the MVB sorting mechanism known as Vps4 which is present in both human cells and in yeast cells. Since the human Vps4 and yeast Vps4 seem to function in the same way, and since powerful molecular genetic approaches can be used in yeast to elucidate how proteins function (some of which are not possible with human cells), we are using yeast to investigate Vps4 function. Once we understand how the yeast Vps4 works, we will be able to test if human Vps4 works the same way. Understanding the MVB sorting mechanism will give us information on how cells prevent uncontrolled growth and division and may also help us find ways of preventing AIDS infection.Read moreRead less
I am a geneticist using multidisciplinary genetic and genomic approaches to study transcriptional mechanisms and molecular pathogenesis in autoimmunity and haematological malignancies.
Development And Pre-Clinical Evaluation Of A Silicone Dressing For Scar Remediation
Funder
National Health and Medical Research Council
Funding Amount
$163,577.00
Summary
This research is aimed at exploiting advanced polymers as a new therapy for patients with burn related scars, as well as people who are genetically predisposed to scarring due to abnormal healing. In order to progress to clinical trials, the technology needs to be tested on an animal scar model. Successful outcome of these tests will allow the industry partner, Tissue Therapies, to proceed with a clinical trial, paving the way to a therapeutic product available for scar treatment.
Elucidation Of The Gene Regulatory Networks That Cause Alzheimer's Disease In Down Syndrome;
Funder
National Health and Medical Research Council
Funding Amount
$782,418.00
Summary
People with Down syndrome have an extra chromosome 21 and all develop Alzheimer's disease. We are able to delete different parts of chromosome 21 in Down syndrome stem cells and turn these cells into the two main cell types of the brain. By comparing the occurrence of Alzheimer disease with gene expression changes in these gene-edited cell types we can identify the gene-regulatory pathways that cause Alzheimer's disease in Down syndrome and identify novel therapeutic targets for sporadic Alzheim ....People with Down syndrome have an extra chromosome 21 and all develop Alzheimer's disease. We are able to delete different parts of chromosome 21 in Down syndrome stem cells and turn these cells into the two main cell types of the brain. By comparing the occurrence of Alzheimer disease with gene expression changes in these gene-edited cell types we can identify the gene-regulatory pathways that cause Alzheimer's disease in Down syndrome and identify novel therapeutic targets for sporadic Alzheimer's disease.Read moreRead less
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
The Proteins Associated With The Neurotrophin Retrograde Transport Signalling Endosome
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
According to estimates taken from the Australian Bureau of Statistics population projection series, during the next forty years the incidence of Alzheimer's disease or a related dementia in Australia is predicted to increase by 254%. One of the key issues in neurobiology is to understand the mechanisms regulating the survival of nerve cells. Nerve Growth Factor (NGF) acts to cause nerve cell survival by being transported from the target tissue to the cell body in a discrete organelle described a ....According to estimates taken from the Australian Bureau of Statistics population projection series, during the next forty years the incidence of Alzheimer's disease or a related dementia in Australia is predicted to increase by 254%. One of the key issues in neurobiology is to understand the mechanisms regulating the survival of nerve cells. Nerve Growth Factor (NGF) acts to cause nerve cell survival by being transported from the target tissue to the cell body in a discrete organelle described as the Signalling Endosome. This process is termed Retrograde Axonal Transport. The signalling endosome is assembled in the nerve terminal and also contains proteins normally activated by NGF known as Second Messengers. Neurodegenerative diseases, such as Alzheimer's disease, occur due to the death of nerve cells and a disturbance of the retrograde axonal transport of NGF may contribute to this death. NGF has been shown to have clinical potential as it can promote neuronal repair and survival after injury. However clinical trials have demonstrated an unacceptable toxicity for this protein. Therefore, another approach taken to produce the restorative benefits of NGF is to stimulate second messenger pathways downstream from the NGF receptor. This approach could provide important new therapeutic potentials as we can target more selective components of these survival pathways and have a greater chance to find less toxic drugs. This project will identify the second messengers normally accompanying NGF from the nerve terminal which promote nerve cell survival. We will describe the way these proteins are recruited to the signalling endosome. Survival of nerve cells requires the activation of these proteins and we shall determine where this occurs. Understanding the molecular basis for the delivery of the retrograde survival signal in neurons is vital if new therapeutic strategies for the treatment of neurodegenerative disease and traumatic nerve damage are to be developed.Read moreRead less