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
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
Early Detection Of Infants And Young Children With Autism
Funder
National Health and Medical Research Council
Funding Amount
$268,250.00
Summary
Autism is a severely handicapping condition adversely affecting social interaction, communication, behaviour, interests, and activities. Autism requires treatment at an early age (before 4 years). Despite finding that parents notice problems with their child's development within the first 2 years, on average diagnoses are made around 6 years of age. Treatment for autism should begin as early as possible to improve outcome. Diagnosis requires specialist assessment and these services are limited. ....Autism is a severely handicapping condition adversely affecting social interaction, communication, behaviour, interests, and activities. Autism requires treatment at an early age (before 4 years). Despite finding that parents notice problems with their child's development within the first 2 years, on average diagnoses are made around 6 years of age. Treatment for autism should begin as early as possible to improve outcome. Diagnosis requires specialist assessment and these services are limited. Therefore it is not possible to undertake such assessments with all children who have developmental problems. This project therefore proposes to evaluate a method for screening large populations of children for autism, thus enabling timely and more appropriate referral to assessment services. Previous work by the investigators has developed a potential screening tool (DBC Early Screen) for autism in young children under 4 years with developmental delay that has high levels of accuracy in identifying those infants and children who are at risk of autism and require specialist assessment. This project proposes to undertake a community field trial to assess the accuracy and reliability of this early screen and to establish its suitability for wide use as a population screening tool. The preliminary testing of DBC Early Screen demonstrated that a community field trial was feasible. The results of this study will facilitate the referral of infants and young children to specialist autism assessment services, thus enabling the commencement of appropriate early intervention for children and their families from an early age.Read moreRead less
Long-term Efficacy Of An Oral Health Promotion Program In The Prevention Of Early Childhood Caries.
Funder
National Health and Medical Research Council
Funding Amount
$165,664.00
Summary
The aim of the project is to test the long-term efficacy of oral health promotion program, the purpose of which is to lower the prevalence of tooth decay among young children. Tooth decay affects approximately 1 in 6 children by age of 3 years and 1 in 2 children by age of 5 years. The disease negatively influences all aspects of quality of life of child. Tooth decay is associated with infection, pain, and frequent hospitalisation. The proposed project is a follow-up of an randomised controlled ....The aim of the project is to test the long-term efficacy of oral health promotion program, the purpose of which is to lower the prevalence of tooth decay among young children. Tooth decay affects approximately 1 in 6 children by age of 3 years and 1 in 2 children by age of 5 years. The disease negatively influences all aspects of quality of life of child. Tooth decay is associated with infection, pain, and frequent hospitalisation. The proposed project is a follow-up of an randomised controlled trial (RCT), which started with enrolment of pregnant women. They were randomised into the test and control groups. Mothers in test group received 3 round of preventive oral health information in the form of anticipatory guidance, the first round at enrolment, the second and third at 6, 12 months of age of child respectively. The information was mailed to their home address. All children were examined at age of 20 months of age. The children in the test group had lower prevalence of tooth decay compared to children in control group, (test group 1,7%, control group 9.6%). While the oral health information was effective in preventing decay at 20 months, longer-term follow-up is highly desirable. Therefore, we plan to follow-up the oral health of the children at 5 - 6 years old. It is anticipated, that 75% mothers from the trial will be contactable and will continue with their participation in the study. A third comparative group of children at the same age will be drawn from database of the South Australian School Dental Services to check if the children in the trial are representative of all SA school children. All children will be examined by dentists or school dental therapists after they enter school. The prevalence of the tooth decay and its mangement will be examined and compared among children from test and control groups and children from community.Read moreRead less
Attracting, preparing, and sustaining quality teachers in early education. This project aims to address the chronic shortage of early childhood teachers in Australia, which is compromising quality and return on investment in early education. The project expects to generate new understandings about this specialist teacher workforce through an innovative, ecological, longitudinal design that will track early childhood teachers’ career trajectories and develop a world-first tool to assess early chi ....Attracting, preparing, and sustaining quality teachers in early education. This project aims to address the chronic shortage of early childhood teachers in Australia, which is compromising quality and return on investment in early education. The project expects to generate new understandings about this specialist teacher workforce through an innovative, ecological, longitudinal design that will track early childhood teachers’ career trajectories and develop a world-first tool to assess early childhood teacher quality. Findings are expected to inform policy— including the Australian Government-endorsed 10-year national Workforce Strategy and the Australian Government's Early Years Strategy— to support the future sustained supply of a quality early childhood teacher workforce and improve outcomes for young children.Read moreRead less
Identification Of The Molecular Hallmarks Of Naevi Progressing To Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Melanomas are amongst the most commonly occurring cancers in Australia with >136,000 people living with a previous melanoma diagnosis. One of the highest risk factors for developing melanoma is having a high number of moles (or naevi). It is therefore important to fully understand how and why naevi develop into melanoma. It is hoped that early detection markers will be identified which will help identify early melanomas and as such improve patient outcome.
Early Detection And Early Intervention For Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$2,088,220.00
Summary
Cerebral Palsy (CP) is Australia’s 5th expensive health condition. Early Detection and effective early interventions are vitally needed to improve long-term outcomes. This fellowship develops and tests novel interventions to optimise neuroplasticity by improving early detection and physical, cognitive, psychological and health outcomes in children with CP. Earlier accurate detection of CP will ensure effective treatments utilise critical periods of brain development.