Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
Gastrointestinal Function And Appetite In Obesity - Acute And Longer-term Effects Of Changes In Energy Intake
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
The prevalence of obesity is assuming epidemic proportions. While weight loss diets help people to lose weight, body weight stabilises over time despite continued dieting. Our research proposal represents a novel initiative with the aim to understand the adaptations in gastrointestinal mechanisms in response to acute and longer-term dietary restriction that compromise weight loss. Ultimately our research will help to develop weight loss strategies that are successful in the long-term.
INVESTIGATING THE VALIDITY OF PRENATAL INSULTS AS RISK FACTORS FOR SCHIZOPHRENIA.
Funder
National Health and Medical Research Council
Funding Amount
$201,100.00
Summary
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical ma ....Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in patients with schizophrenia it would suggest that these long lasting disturbances could result from problems during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of the underlying causes of schizophrenia.Read moreRead less
Effects Of The Fatty Acid, Lauric Acid, On Energy Intake And Gut Motor And Hormonal Function In Health And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
Obesity is largely due to energy intake exceeding energy expenditure, thus, strategies that reduce energy intake will result in weight loss. We discovered recently that the fatty acid, lauric acid, markedly reduces energy intake. Our studies will determine the effects of lauric acid on energy intake and body weight reduction in obese subjects. The research is a new initiative and explores the potential of lauric acid as a novel, nutrient-based and side-effect free approach to obesity management.
Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.Read moreRead less
The Role Of A Low Emulsifier Diet To Treat Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$447,603.00
Summary
Currently, there are no specific diets known to treat Crohn’s disease (CD). Initial lab- and animal-based studies have indicated emulsifiers added to food drive inflammation in CD, but no human trials completed. This study will design and feed high and low emulsifier diets to healthy and CD subjects and measure markers of inflammation. This will establish the role of a low emulsifier diet to treat CD.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.
Effects Of Dietary Protein On Gastrointestinal Function: Implications For The Regulation Of Energy Intake In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$677,157.00
Summary
Obesity is largely due to energy intake exceeding energy expenditure. The CI has reported that dietary protein markedly reduces energy intake but the mechanisms underlying this effect remain unknown. The proposed studies will determine whether gastrointestinal mechanisms are involved in the regulation of appetite and energy intake and how they relate to body weight reduction in obese subjects. The research represents a unique approach to the management of obesity and health.