Mechanisms Underlying Efferent Feedback In The Vestibular System
Funder
National Health and Medical Research Council
Funding Amount
$491,475.00
Summary
The balance system has a remarkable, but poorly understood capacity for self-repair. An intrinsic feedback mechanism, the Efferent Vestibular System or EVS is thought to play a major role in this self-repair. Surprisingly, we know little about EVS function in animals or humans. We will study the EVS in mice and humans to gain a better understanding of how it works. This information will then drive the design of therapies that improve and restore balance in disease, injury, or ageing.
Gene Therapy For Preventing Progressive Sensorineural Hearing Loss And Restoring Hearing
Funder
National Health and Medical Research Council
Funding Amount
$549,848.00
Summary
This proposal aims to study the clinical feasibility and safety of gene therapy in the guinea pig cochlea for preventing progressive hearing loss and restoring hearing. Two cell survival genes (GDNF and BDNF) will be studied for preserving sensory (hair) cells and hearing nerves, while a gene called Atoh1 will be investigated for its ability to regenerate new hair cells and restore hearing after the onset of progressive hearing loss.
Our vestibular system provides us with the important sense of balance. When it fails we suffer debiltating bouts of vertigo and dizziness. A great deal is known about how balance signals are sent from the inner ear to our brains, but virtually nothing is known about the important signals the brain sends to the inner ear. In this study we will use a new perparation develped in our laboratory to examine how these essential brain signals control the function of our balance organs.
Development Of Human Sensory Receptors Of The Inner Ear
Funder
National Health and Medical Research Council
Funding Amount
$418,281.00
Summary
Normal development of our special sense organs is crucial for sight, taste, hearing, and balance. The balance system mediates important postural and eye reflexes that are essential for movement and vision. Abnormal development of the balance system results in dizziness, vertigo, gait deficits, and impaired learning and reading ability in children. This study will investigate how the organs of balance mature and connect with nerve fibres of the inner ear during human development.
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Microenvironmental Regulation Of Blood Cells By Retinoic Acid Receptor Gamma.
Funder
National Health and Medical Research Council
Funding Amount
$958,428.00
Summary
Vitamin A deficiency causes profound effects in humans, with anaemia and an inability to fight infection being consequences of vitamin A deficiency on blood cells. We have evidence that these effects of vitamin A deficiency occur via one of the receptors for vitamin A. Furthermore, these effects are due to changes in the non-blood cells that help to make blood cells. By understanding how this occurs we may identify better treatments for patients with impaired immune systems.
The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
The Role Of EphrinB1 Reverse Signalling In Osteogenic Differentiation During Skeletal Development And Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$567,292.00
Summary
The present proposal will identify the importance of ephrinB1 during the deregulation of bone remodelling that occurs in osteoporosis, by deleting ephrinB1 in committed osteoblast precursor cells in a mouse model of osteoporosis. Knowledge gained from this proposal could potentially translate into alternative therapeutic treatment strategies for patients with osteoporosis with the use of Eph/ephrin targeted drugs currently being developed for cancer treatment.
B1a B Cells: Atheroprotective Mechanisms And Therapeutic Application
Funder
National Health and Medical Research Council
Funding Amount
$547,180.00
Summary
Atherosclerosis-related heart attacks and strokes remain leading causes of global deaths despite use of potent lipid-lowering drugs. Thus, another therapeutic option is urgently needed. Our laboratory found that B1a B cells protect against atherosclerosis. We will study the therapeutic efficacy of expanding B1a cells by different approaches in atherosclerosis. Our proposal for clinical translation is to reduce mortality from atherosclerosis-based heart attacks and strokes.