The Involvement Of The Kynurenine Pathway In Blood Brain Barrier Disruption And Its Relevance For Neuroinflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$597,797.00
Summary
We aim to study the involvement of molecules deriving from the degradation of the essential amino acid tryptophan on the breakdown of the ñblood-brain barrierî (the cellular wall separating blood and brain) that is observed in several major brain diseases. Using specific drugs blocking the production or the effects of these toxic compounds we expect to be able to preserve the integrity of the blood brain barrier and so to limit brain inflammation and neuronal loss.
Pathogenesis And Therapeutic Modulation Of Aggressive Behaviour In A Mouse Model Of Autism Spectrum Disorder
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive behaviour is common in autism patients and can have severe consequences on education and employment opportunities. These mice also show excess dampening of brain function (inhibition). This project will test if aggression in these mice is caused by altered inhibition.
Gene-environment Interactions Modulating Cortical And Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$618,300.00
Summary
A feature of many major brain disorders, including schizophrenia and dementia, is disruption of cognition. A key brain area impacted in such cognitive disorders is the prefrontal cortex. This project will use clinically translatable touchscreen to understand how this aspect of brain dysfunction causes abnormal cognition. We will investigate the mechanisms involved, using highly innovative approaches, which will contribute to the development of new treatments for such cognitive disorders.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Understanding the contribution of neuroinflammation in acute and chronic neural injury. A major focus of this project will be investigating the involvement of neuroinflammation in neural cell damage. It will explore how neuroinflammation contributes to this damage in both acute and chronic neuropathologies.
Regulation of neuronal cell death signalling for the treatment of neurodegenerative diseases. The progression of neurodegenerative diseases, such as Alzheimer's and motor neuron diseases, are often underpinned by neuronal cell death-signalling. This project aims to characterise molecules that regulate cell death signalling, thereby increasing our knowledge of how neuronal cell death can be inhibited.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$330,735.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100323
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The regulation by transcription factor phosphorylation upon the myelinating process. The project will investigate the novel molecular events that control the myelinating process, which is essential for normal nervous system function. Outcomes of this project may aid the development of novel interventions to improve control of demyelinating diseases, which represent a substantial socio-economic burden.
A Novel Mechanism For The Maintenance Of Catecholamine Synthesis
Funder
National Health and Medical Research Council
Funding Amount
$356,250.00
Summary
Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the dru ....Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the drugs all affect the catecholamine systems. Tyrosine hydroxylase controls catecholamine synthesis and it is activated in both the acute and adaptive phases of the stress response in order to replace catecholamines that have been secreted. Tyrosine hydroxylase is activated by protein phosphorylation in the acute phase and by the synthesis of new tyrosine hydroxylase in the adaptive phase. We have now discovered an additional and novel phase that we refer to as sustained tyrosine hydroxylase activation. This phase spans at least the period between the acute (mins) and adaptive phases (days). It involves the sustained phosphorylation of tyrosine hydroxylase and its mechanism appears to differ from the other two phases. In this project we will answer three questions. Does sustained tyrosine hydroxylase activation: 1 Occur in response to many stimuli and in many catecholamine cell types? 2 Occur by a single mechanism, different to the other phases, in all circumstances? 3 Play a role in the control of blood pressure and depression? This project will provide fundamental data about the mechanisms and consequences of sustained tyrosine hydroxylase activation, which is a part of the stress response not previously discovered. The data may impact on the way we design drugs to control stress responses, including antidepressants and antihypertensives.Read moreRead less