Mechanisms By Which Aging Induces Constipation In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$369,717.00
Summary
Chronic constipation is one of the most common reasons why the elderly community seek medical attention. There is now strong evidence to suggest that the high prevalence of constipation in the elderly is likely due to a dramatic loss of specific nerves that lie in the wall of the colon. This project will use latest imaging technologies to identify the mechanisms by which these nerves are impaired with age that lead to constipation in the elderly.
Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
Age-and Species-related Regulation Of Host Inflammatory Responses In Falciparum And Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$323,640.00
Summary
Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines ....Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines for adults and children.Read moreRead less
Assessing The Role Of The N-terminus Of The Prion Protein, Emphasising Constitutive Cleavage, In Normal Function And Pathogenesis, As Well As Defining The Relationship Between Intensity Of Surveillance And Sporadic CJD Incidence.
Funder
National Health and Medical Research Council
Funding Amount
$387,469.00
Summary
As a neurologist undertaking research into prion diseases over an extended period, I have been able to lead and participate in many projects that have made significant contributions, such as validation of new diagnostic tests for Creutzfeldt-Jakob disease (CJD), assessment of potential therapeutics, provide insights into the normal function of the prion protein and the underlying pathways causing cellular damage and determine the real significance of apparent clusters of sporadic CJD.
The Role Of The Complement System In Neurodegeneration And The Therapeutic Potential Of Complement Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
This project aims to identify the role of immune and inflammatory components in the pathology of neurodegenerative disease. Additionally, this research will determine whether a new class of novel anti-inflammatory drugs can alter the neurodegenerative process. This will allow for an increased understanding of the biology of neurodegenerative disease, and also may lead to the development of new treatments for conditions such as Parkinson’s disease, Huntington’s disease and motor neuron disease.
Circuit Class Therapy For Rehabilitation Clients. A Pragmatic Randomized Controlled Trial Of Therapy Intensity (CIRCIT).
Funder
National Health and Medical Research Council
Funding Amount
$526,361.00
Summary
Loss of independence is common after stroke, and may lead to reduced quality of life and admission to nursing home care. We will investigate if an increased amount of rehabilitation following stroke leads to improved mobility. Two ways of delivering more intense rehabilitation will be compared with usual care to find out which leads to improved physical mobility, and how they compare economically. This will allow health service providers to optimise services and will benefit people with stroke.
Flecainide In Amyotrophic Lateral Sclerosis - A Neuroprotective Strategy
Funder
National Health and Medical Research Council
Funding Amount
$593,275.00
Summary
This project will provide clinical trial information related to the potential neuroprotective properties of flecainide in motor neurone disease patients. A potential therapeutic response would provide impetus for a larger scale, multi-centre clinical trial. In addition to providing information about potential mechanisms of neurodegeneration and their treatment, new quantifiable measures will be further developed to objectively monitor MND patients in a clinical trials setting.
Parkinson's disease is a progressive, disabling, age-associated neurological disorder with no known cure. Several genes have been identified as causing Parkinson's disease, although mutations in leucine-rich repeat kinase2 (LRRK2) are by far the most common. The studies we propose will identify the cellular proteins that interact with LRRK2 to cause Parkinson's disease. These proteins may be amenable to future therapeutic manipulation.
Postsynaptic Signalling Systems That Sustain The Nerve-muscle Synapse
Funder
National Health and Medical Research Council
Funding Amount
$598,041.00
Summary
Neuromuscular junctions (NMJ) are the synapses through which motor nerves control our voluntary muscle cells. This project will investigate the molecular signalling system between nerve and muscle that helps maintain healthy NMJs. Normal ageing involves a progressive decline in muscle strength, often leading to loss of independence in the elderly. We will use a mouse model to test whether a breakdown of the NMJ signalling system contributes to the loss of strength in old age.