Does IRAP Contribute To Alzheimer's Disease Pathology?
Funder
National Health and Medical Research Council
Funding Amount
$743,042.00
Summary
Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or pro ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progression of Alzheimer’s disease pathology.Read moreRead less
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many post-transcriptional events that govern how efficiently the genetic information is ultimately converted to protein molecules. In this project we will investigate the molecular mechanisms of several proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), that appear to play regulatory roles in many of these steps. These proteins appear to affect the longevity and replication of cells, the important chemical changes that take place in RNA after it is transcribed and before it is translated, the movement of the modifed RNAs through the cell and the efficiency of translation. Because of these central functions they are involved in development of tissues such as the brain, and in diseases including lung, skin and brain cancers, and rheumatoid arthritis. In this project we will focus on two RNA molecules, one vital for myelination in the central nervous system and the other for memory.Read moreRead less
Obesity In The Elderly: Impact Of Weight Loss Therapy On Physiology And Function.
Funder
National Health and Medical Research Council
Funding Amount
$613,213.00
Summary
The aim of this study is to assess the safety, tolerability, weight-loss efficacy, change in lean body mass and impact of cognition of three approaches to treat obesity in the elderly. We will compare dietary advice, an energy reduced diet and a very low calorie diet. All three groups will also have an exercise program. This study will be of major assistance in developing management guidelines for obesity in the elderly, which will likely be an emerging public health issue.
Improving Weight Loss By Intermittent Use Of Very Low Energy Diet: The TANGO Diet Trial (Temporary Phases Of Accelerated Weight Loss For Noticeably Greater Outcomes)
Funder
National Health and Medical Research Council
Funding Amount
$660,736.00
Summary
Very low energy diet (VLED) is being increasingly used for the treatment of obesity, but the resultant weight loss is usually transient, partly because it induces powerful adaptive responses that inhibit weight loss and promote regain. We have shown that 'taking a break from dieting' for 2 weeks reduces these adaptive responses. In this project we will thus test whether weight loss outcomes with VLED can be improved via intermittent use, where periods on the VLED are alternated with 'breaks'.
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
Osteocytes (OY) are the most abundant cell type in bone whose high density and viability are essential for healthy bone. We have found that vitamin K, vitamin D and strontium, promote human OY differentiation. We will test these in novel models of human OY differentiation and survival, and in animal models of bone loss associated with vitamin D deficiency, menopause and glucocorticoid treatment. Our work will lead to a better understanding of human OY and give a new approach to treat osteoporosi ....Osteocytes (OY) are the most abundant cell type in bone whose high density and viability are essential for healthy bone. We have found that vitamin K, vitamin D and strontium, promote human OY differentiation. We will test these in novel models of human OY differentiation and survival, and in animal models of bone loss associated with vitamin D deficiency, menopause and glucocorticoid treatment. Our work will lead to a better understanding of human OY and give a new approach to treat osteoporosis.Read moreRead less
Identification Of Microbiome Control Of Weight Loss During Dietary Intervention In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$644,667.00
Summary
We will develop diagnostic tests that enable prediction of the optimal weight loss diet for patients. Obesity is a growing problem in Australia and weight loss is of proven health benefit. Dieting is capable of delivering useful weight loss but long term success rates are poor. The variable success rates are linked to differences in gut microbiota. Diagnostic tests based on the gut microbiota in stool samples will allow identification of the optimal weight loss diet for individuals.
Accelerated Longterm Forgetting In Children With Genetic Generalised Epilepsy: An Investigation Of The Temporal Trajectory And Contribution Of Executive Skills.
Funder
National Health and Medical Research Council
Funding Amount
$107,204.00
Summary
The aim of this study is to determine which factors influence forgetting in typically developing children and in children with epilepsy. Specifically, we want to establish how forgetting occurs over time and whether it is influenced by other cognitive/thinking skills, such as strategies used to remember information, attention or resistance to interference. Moreover, we are interested in whether retention rates are affected by different types of learning materials (i.e. visual versus verbal).
The Role Of Mitochondrial DNA In Age-related Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$260,475.00
Summary
Hearing loss is an extremely common and under-studied age-related disability, affecting 39% of Australians aged 50 years or older. Both genetic and environmental factors may contribute to the development of age-related hearing loss. Human genetic material (DNA) resides in two places in body cells; the nucleus and in organelles called mitochondria. This is due to the fact that mitochondria were derived from bacteria that were engulfed by the cell back in primordial life. Although this genetic mat ....Hearing loss is an extremely common and under-studied age-related disability, affecting 39% of Australians aged 50 years or older. Both genetic and environmental factors may contribute to the development of age-related hearing loss. Human genetic material (DNA) resides in two places in body cells; the nucleus and in organelles called mitochondria. This is due to the fact that mitochondria were derived from bacteria that were engulfed by the cell back in primordial life. Although this genetic material is different to nuclear DNA, it has an essential role in helping to provide energy for the cell. Genetic mutations in the DNA residing in the mitochondria have been associated with a number of conditions, usually affecting tissues that require large amounts of energy, such as the brain, muscle, heart, retina and the cochlea of the ear. The commonest clinical manifestation of mitochondrial disease is thought to be hearing loss. This project investigates the role that abnormal mitochondrial DNA plays in the development of hearing impairment by studying subjects from a representative Australian community who participated in a large population study of hearing loss. We will assess whether different sectors of mitochondrial DNA predispose particular individuals to the development of hearing loss or accelerate its onset. The Blue Mountains Hearing Study is able to take into account other factors known to be associated with hearing loss (industrial noise exposure, diabetes, smoking).Read moreRead less
How well people perform in everyday situations is often determined by memory function. When required to perform under stress memory performance is often affected. The effect of a psychological stress test on memory function in healthy volunteers and the ability of a dietary supplement, tyrosine, to prevent the effects will be studied. The data may suggest that depletion amino acids is responsible for the decrements in performance that are evident after an acute stressor.