The Role Of Interferon Signalling In The Regulation Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
This project focuses on the role that inflammation plays in the progression of the type of neural injury seen in stroke victims. This project targets a specific pathway that is thought to be involved in the regulation of general inflammation but has not been greatly investigated in terms of the neural injury seen in stroke. Understanding the actions of this pathway may lead to future therapies that can be used to prime the brain to react in a positive way to stroke.
The Effect Of Smoking On The Exacerbation Of Stroke: Oxidative Stress Involvement And Cerebrovascular Response.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
This grant addresses whether smoking contributes to the severity of stroke outcome. The studies outlined in this proposal will contribute significantly in our understanding of how smoking contributes to the progression of stroke. The understanding of the involvement of smoking in the progression of stroke will be of great benefit in the development of improved stroke patient management.
Mechanisms Of Immune Complex-mediated Inflammation In The Cerebral Microvasculature
Funder
National Health and Medical Research Council
Funding Amount
$146,500.00
Summary
Immune complexes are formed when an antibody binds to the molecules it is directed against. Normally, this is important for fighting infection. However in some autoimmune diseases, inappropriate formation of immune complexes can be damaging to our own tissues. This damage occurs because immune complexes attract white blood cells to the areas where they form. Many tissues can be affected by this process. However, we know very little about the effects of immune complexes specifically in the brain. ....Immune complexes are formed when an antibody binds to the molecules it is directed against. Normally, this is important for fighting infection. However in some autoimmune diseases, inappropriate formation of immune complexes can be damaging to our own tissues. This damage occurs because immune complexes attract white blood cells to the areas where they form. Many tissues can be affected by this process. However, we know very little about the effects of immune complexes specifically in the brain. This is important because immune complexes are found in the brain in diseases such as lupus. Therefore the aim of this proposal is to determine how immune complexes induce damaging inflammation in the brain.Read moreRead less
The Kynurenine Pathway Chemokines And MIC-1 In The Pathogenesis Of AIDS Dementia Complex.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
This proposal will examine the mechanisms by which HIV and other brain disorders such as encephalitis damage the brain. Further understanding of the biochemical pathway involved will lead to the possibility of novel drug therapy for these disorders.
Intraocular Transplantation And Regeneration Of Retinofugal Pathways In Rodents
Funder
National Health and Medical Research Council
Funding Amount
$370,937.00
Summary
In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replen ....In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replenishing nerve cells in damaged CNS gray matter, and new methods are also required to help reconstruct fibre tracts after injury. Using the visual system as an experimental model, the aims of the proposed work are to develop novel transplantation and surgical strategies to: (i) Incorporate new cells into retinae that have been selectively depleted of endogenous neurons (ii) Promote the effective regeneration of large numbers of adult retinal axons through prosthetic peripheral nerve bridging grafts and into host CNS distal to the injury. The results obtained from the first series of studies will not only be of direct relevance to the future treatment of human retinal degenerative disorders, but will also increase our overall understanding of how best to ensure the differentiation and stable integration of different types of transplanted cells within the compromised host CNS. The second series of experiments should lead to an entirely new approach to nerve pathway reconstruction, relevant to both brain and spinal cord injuries. The ultimate aim of this experimental work is to improve the management and treatment of human CNS injury and disease, leading to better functional recovery and rehabilitation.Read moreRead less
The Leucine Rich Repeat Kinase 1 And 2 Genes Are Modulators Of Alternative Splicing - Implication For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$583,809.00
Summary
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two common causes of dementia and neurodegeneration. Through positional cloning, we have identified the leucine rich repeat kinase (LRRK1) 1 gene as a modulator of alternative splicing. We have subsequently shown that its homologue, LRRK2 has a similar biological activity. We propose to study the the genetic and biochemical role of LRRK1 and LRRK2 in neurodegeneration in terms of its effect in splicing.
Cell Type Specification In Developing CNS: Functional Analysis Of Sox14
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are ....The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are maintained in the adult. This has been largely due to a lack of efficient and reliable methods to identify and study interneurons. We have previously discovered that a gene termed Sox14 is active in distinct interneuron groups in the embryonic brain and spinal cord. Sox14 is a member of the Sox gene family, many of which act as genetic switches to control cell and tissue development. We found that Sox14 has been extremely well conserved throughout evolution and is active in similar interneuron groups in a number of animal species. These studies led us to hypothesise that Sox14 controls a critical molecular step in the generation of certain interneurons that may be involved in reflexes, locomotion or motor coordination. In this project, we will investigate both the role of Sox14 in interneuron development and the functions of interneurons in which this gene is active. We will do so by combining modern molecular and genetic techniques with physiological approaches. This project will reveal critical molecular steps in CNS development and determine the functions of a specific group of interneurons. To this end, we will generate mouse strains in which a specific group of interneurons are genetically marked and can be manipulated during development. We envisage that these mice with 'modified brain circuits' will become unique resources for future investigations of selected interneuron types and their functions.Read moreRead less
Emerging Infectious Neurological Diseases In Australia; From Enhanced Recognition To Improved Response
Funder
National Health and Medical Research Council
Funding Amount
$189,384.00
Summary
Infectious neurological diseases(IND) such as encephalitis are severe and frequently cause long term disability. New IND like Zika pose a real threat. During his PhD, Dr Britton identified outbreaks of encephalitis in children and described serious consequences. Here, Dr Britton proposes to extend his work across all ages, include other types of IND and explore novel methods to detect outbreaks. He will work with experts at leading national research centres in surveillance and infectious disease