The Developmental Vitamin D Model (DVD) As An Animal Model For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$258,075.00
Summary
Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. ....Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. Schizophrenia is a developmental disease that presents in adolescence and affects about 1% of the world's population. To date we have shown increased amounts of schizophrenia in offspring from mothers that had low blood vitamin D levels during pregnancy or who had inadequate vitamin D intake. Early signs therefore appear promising but obviously more research is required to confirm this idea. Our studies in animals have revealed that by restricting vitamin D intake in pregnant rats, newborns have brains that develop differently. Most notably lateral ventricle volume is increased, a key anatomical finding in patients with schizophrenia. When these animals become adults the increase in lateral ventricles persists. Also when we explore the behaviour of these animals we find a deficit in learning and memory similar to that seen in many schizophrenic patients. Furthermore when we expose these animals to agents that induce psychosis or agents that block psychosis in patients we see a heightened sensitivity in animals that were deprived of this vitamin in utero particularly in locomotion. These behavioural findings are consistent with the best animal models for schizophrenia. At a mechanistic level they indicate an abnormality in the two major neurotransmitters in the brain that have been consistently linked with this disease, dopamine and glutamate. The experiments outlined in this application will attempt to establish the neurochemical basis for these altered behaviours.Read moreRead less
Social Behaviour In Rats Developmentally Deficient In Vitamin D: Modelling The Negative Symptoms Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$360,927.00
Summary
We are exploring low maternal vitamin D as a biological explanation for a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year world wide. Developmental vitamin D (DVD) deficiency in rats leads to long term changes in brain development and behaviour. The aim of this research is to examine social behaviour in DVD deficient rats as a model of negative symptoms of schizophrenia and establish the neurochemical basis for this altered behaviour
Plasticity In The Thalamic Reticular Nucleus During Normal And Altered Postnatal Development
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
Thalamic centres concerned with vision send information through the thalamic reticular nucleus to multiple cortical areas in which different aspects of the visual world are analysed. These cortical areas in turn send connections back through the reticular nucleus to the thalamus. Cortical function ultimately depends on the correct connections being established between the sensory receptors and the thalamus and between the thalamus and cortex. Far from being merely a relay station of peripheral s ....Thalamic centres concerned with vision send information through the thalamic reticular nucleus to multiple cortical areas in which different aspects of the visual world are analysed. These cortical areas in turn send connections back through the reticular nucleus to the thalamus. Cortical function ultimately depends on the correct connections being established between the sensory receptors and the thalamus and between the thalamus and cortex. Far from being merely a relay station of peripheral sensory information the dorsal thalamus modifies and interacts with the flow of information around the brain. The reticular nucleus forms an integral part of this information flow. How these connections develop and are modified by disturbance to the visual pathway is crucial to our understanding of brain function. To this end, we will study the connections between three areas of the brain concerned with vision, the thalamic reticular nucleus, the thalamus and the visual cortices. We will focus our study on the development of the reticular nucleus and the importance of a normal visual environment in establishing the proper connections between different brain areas. The importance of studying normal and abnormal development is that it can provide a description of the kinds of experience leading to specific types of neural abnormalites. This information tells us the degree to which connections are malleable and is of potential clinical importance.Read moreRead less
Understanding The Role Of B Cells In Gastric Cancer For The Design Of New Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$696,383.00
Summary
Gastric cancer is the 2nd most common cause of cancer-related death worldwide. Our laboratory has previously established clinically relevant mouse model of gastric cancers, and our preliminary results indicate a strong link between B cell tumor infiltration and gastric cancer progression. In this project, we aim to elucidate the role of B cells in gastric cancer and determine whether B-cell targeted therapy alone or in combination with chemotherapy can be beneficial against this malignancy.
Novel Signalling Pathways Leading To The Activation Of Glomerular Parietal Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Chronic kidney disease (CKD) is a major health problem in Australia. CKD patients have very limited therapeutic options. The majority of diseases that lead to CKD are associated scarring of the renal filters. Parietal epithelial cells reside in these filters and play key roles in scarring development. However, the molecular mechanisms that lead to scarring in these renal filters remain unclear. This proposal aims to identify molecular pathways that may serve as future therapeutic targets.
Robotic Surgical System For Image Guided Non-invasive Focused Ultrasound Induced Ablation Of Liver Cancers
Funder
National Health and Medical Research Council
Funding Amount
$582,231.00
Summary
According to National Cancer Institute, liver and bile duct cancers are the fifth most common cancer in men and the seventh in women. Due to poor prognosis involving surgery, radiotherapy and chemotherapy, our aim is to develop a novel image-guided, radiation-free, non-invasive robotic HIFU system with means for compensation of organ movement during treatment. The objective is to produce damage to the target in a predictable and reproducible manner while sparing overlying surrounding tissues.
Genetic Adaptations Of Mycobacterium Tuberculosis For Intracellular Survival
Funder
National Health and Medical Research Council
Funding Amount
$187,677.00
Summary
Tuberculosis (TB) remains a significant global public health problem and new approaches to its treatment and prevention are urgently needed. The disease is caused by infection with Mycobacterium tuberculosis, a slow growing organism that lives within cells. How it adapts to survive in this intracellular environment is unknown. Recently the complete genome of M. tuberculosis was sequenced and new techniques developed for manipulating its genes. We plan to use these techniques to identify genes th ....Tuberculosis (TB) remains a significant global public health problem and new approaches to its treatment and prevention are urgently needed. The disease is caused by infection with Mycobacterium tuberculosis, a slow growing organism that lives within cells. How it adapts to survive in this intracellular environment is unknown. Recently the complete genome of M. tuberculosis was sequenced and new techniques developed for manipulating its genes. We plan to use these techniques to identify genes that are more active within the cells. Genes are controlled by short sequences of preceding DNA called promoters. If these promoters are randomly placed in front of readily identifiable reporter genes and inserted into a suitable host strain, it is possible to select for those promoters expressed only inside cells and then identify the promoter and its gene by sequence analysis. We plan to use two types of reporter genes. First, we shall place the M. tuberculosis DNA containing promoters before the gene for a naturally fluorescent protein within the M. bovis BCG host strain and then infect macrophages. If the promoters are switched on inside the cell, the macrophages will become green and can be selected and the promoter identified. After several rounds of selection the promoter is isolated and identified. Second, we shall select the promoters by their ability to produce a protein that is on the surface of the bacterium. We will use these intracellular genes to make better vaccines against TB. Genes that enhance intracellular survival may contribute to the virulence of the TB organism. By removing these genes we can make an attenuated organism suitable as a vaccine. We will test for reduced virulence by growth inside cells in mice. We will also use the intracellular promoter to improve the current BCG vaccine. Proteins expressed inside the cell may also be targets for new TB drugs.Read moreRead less