Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
How Does Paternal Obesity Influence Offspring Glucose Tolerance?
Funder
National Health and Medical Research Council
Funding Amount
$503,398.00
Summary
Obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. We have shown that normal females mated with obese fathers consuming high fat diet, produce offspring who develop glucose intolerance and impaired insulin secretion. This work will examine the mechanisms underlying this effect in the rat, testing a novel role for environmental factors in the father on disease in offspring that may be relevant to the growing obesity epidemic.
The Structure And Function Of The Apical Domain In Insulin Secreting Beta Cells.
Funder
National Health and Medical Research Council
Funding Amount
$571,741.00
Summary
Loss of control of insulin secretion is causal in diabetes and therefore its understanding is a key goal to shed light on the disease. We have recently identified a new domain in the insulin secreting cells, called the apical domain. This proposal will define the role of this apical domain in controlling insulin secretion. The outcomes could provide new insights into how diabetes develops and new targets for therapies.
The Preferential Release Of Young Insulin Secretory Granules.
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
The aim of this study is to investigate the cause of reduced glucose induced insulin secretion in type 2 diabetes. In pancreatic beta-cells, insulin is packaged and stored in secretory granules (SGs). Upon stimulation, these SGs deliver insulin to the bloodstream. It is known that insulin SGs exist in two functionally distinct pools; and one pool is preferentially secreted upon stimulation. How a cell can differentiate the two SG pools is unclear, and we will address this issue in this project.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
Studies Of The Effects Of Asymmetric Hearing Loss On The Brain
Funder
National Health and Medical Research Council
Funding Amount
$920,076.00
Summary
Hearing loss impairs the normal development and maintenance of auditory pathways. Irreversible pathologies persist when hearing is not restored in a timely manner. While cochlear implantation is the accepted treatment for profound sensorineural hearing loss, there is significant variability in outcomes. Some of this variability is linked to the degree of hearing asymmetry. Thus, we propose to study brain changes in the auditory system that accompany asymmetric hearing impairment.
SENSORIMOTOR AND AUTONOMIC DYSREGULATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$50,406.00
Summary
Specific genetic mutations can lead to widespread changes in the body. Here we are looking at the congenital Hereditary and Sensory Autonomic Neuropathies, the most common of which primarily affects Eastern European Jews. Affected individuals have difficulty walking and controlling their blood pressure, and also have an indifference to pain. This series of experiments aims to increase our understanding of the underlying neurophysiological disturbances.
Information Encoding By Temporal Structure Of Afferent Spike Trains
Funder
National Health and Medical Research Council
Funding Amount
$231,175.00
Summary
Our ability to sense, discriminate and interpret touch stimuli underpins some of the most crucial functions of the human hand that relate to object exploration and manipulation. The fundamental mechanism of how nerve impulses generated by tactile receptors are interpreted by the nervous system is not understood. Only by discovering the underlying neural encoding mechanisms can we appreciate the functional impairments in patients and learn to identify them before they become widespread and irreve ....Our ability to sense, discriminate and interpret touch stimuli underpins some of the most crucial functions of the human hand that relate to object exploration and manipulation. The fundamental mechanism of how nerve impulses generated by tactile receptors are interpreted by the nervous system is not understood. Only by discovering the underlying neural encoding mechanisms can we appreciate the functional impairments in patients and learn to identify them before they become widespread and irreversible.Read moreRead less
Early Indicators Of Noise Injury: Are Decreased Auditory Processing Skills Evident In Noise-exposed Adults Prior To Diagnosis Of Hearing Loss?
Funder
National Health and Medical Research Council
Funding Amount
$367,605.00
Summary
Recent research indicates that noise-exposed individuals with similar hearing thresholds to non-noise exposed counterparts are more likely to have diminished temporal and spectral auditory processing abilities. This research aims to determine the relationship between noise exposure levels and auditory processing difficulties; the influence of musical training in ameliorating these difficulties; and a neurological model of causation, operation and possible remediation of these difficulties.
Vascular And Neurogenic Determinants Of Hypertension In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,142.00
Summary
You are as old as your arteries, and people with kidney disease have arteries that age fast. They also have overactive sympathetic nerves, and it is not clear if the blood vessels or nerves are responsible for the high blood pressure that puts strain on the heart and other organs of these patients. We will use an animal model to determine if therapy for hypertension reduces the stiffness of blood vessels or elevated nerve activity. Our results will enable better treatments for kidney failure.