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Structure-based Drug Design For Neuroprotection From Traditional Chinese Medicine
Funder
National Health and Medical Research Council
Funding Amount
$245,968.00
Summary
In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative di ....In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative disease.Read moreRead less
A Novel Mechanism For Therapeutically Modulating Neurotransmitter-activated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$667,529.00
Summary
This project aims to elucidate the mechanisms by which macrocyclic lactones bind to brain ion channel receptors. This will reveal fundamental new insights into the operation of these receptors and will have important implications for the design of novel treatments for a variety of central nervous system disorders.
Inhibitory Neurotransmitter Receptors As Therapeutic Targets For Chronic Pain And Anxiety Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
There are currently few effective long-term treatments for chronic pain and anxiety disorders. Here we propose to develop innovative therapies for both of these debilitating neurological disorders. In addition, we plan to improve our current understanding of how these disorders occur in the first place. This may identify novel potential therapeutic strategies for treating pain, anxiety and a host of other neurological disorders.
Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in t ....Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in the development of tolerance. Modulation of analgesia by the immune system has not been systematically studied and provides a potentially fertile ground for the development of new techniques in the management of clinical pain.Read moreRead less
From rehabilitation to recovery after stroke : a model to optimise consumer and carer involvement. The National Research Priorities include 'ageing well, ageing productively'. Within this priority, it is necessary to be inclusive of those who have ongoing disabilities and/or chronic disease. This project aims to facilitate healthy lifestyles and community involvement in a group who have significant barriers to achieving their potential. The high incidence of depression and poor quality of life i ....From rehabilitation to recovery after stroke : a model to optimise consumer and carer involvement. The National Research Priorities include 'ageing well, ageing productively'. Within this priority, it is necessary to be inclusive of those who have ongoing disabilities and/or chronic disease. This project aims to facilitate healthy lifestyles and community involvement in a group who have significant barriers to achieving their potential. The high incidence of depression and poor quality of life in stroke survivors and their carers emphasises the need to enhance wellness in these people. The study will develop a model for promoting recovery and community reintegration in stroke survivors, with the goal of enabling stroke survivors and their carers to actively participate in the community and pursue personal goals.Read moreRead less
Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in ....Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in fear learning will enhance our ability to develop better therapeutic approaches for treating anxiety and preventing relapse, potentially through a gender-specific approach. The studies outlined in this proposal will have implications for promoting and maintaining good health.Read moreRead less
What is normal brain ageing? An investigation of changes in brain structure and cognition in mid-life. Pathological brain changes associated with cognitive decline later in life become detectable in the 40s and sometimes earlier, yet little is known about what constitute normal brain ageing in midlife. Using a number of neuroimaging techniques, this project will develop a detailed map of brain and cognitive ageing in middle-age and their predictors.
The development of the social brain in early childhood. This project aims to understand how the human brain develops social and emotional understanding. The brain has remarkable abilities for understanding our social environment, such as inferring other people’s thoughts and feelings. This project will use neuroscience techniques to investigate how brain networks combine to produce social understanding, how this changes throughout child development, and how it relates to complex social behaviour ....The development of the social brain in early childhood. This project aims to understand how the human brain develops social and emotional understanding. The brain has remarkable abilities for understanding our social environment, such as inferring other people’s thoughts and feelings. This project will use neuroscience techniques to investigate how brain networks combine to produce social understanding, how this changes throughout child development, and how it relates to complex social behaviours. This project’s findings could be used to develop educational programmes that enhance empathy and co-operation, strengthen family relationships, promote social inclusion and reduce maladaptive behaviours. It could also guide intervention in brain disorders that affect social understanding.Read moreRead less
The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will ....The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will be the first to comprehensively advance our understanding of the unique role of sex hormones in shaping the adolescent female brain. It will provide critical understanding of how individual differences in hormonal factors increase risk for emotional problems in females, and inform treatment strategies.Read moreRead less
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less