Parkinson's Disease is caused by injury to a group of brain cells called the Basal Ganglia. Our current ideas about how this part of the brain works is dominated by a well know theory. This theory requires that the output pathway of the basal ganglia to have a negative or inhibitory influence on its target. However there are numerous reasons why this would be unlikely, including some recent evidence from experiments in our laboratory. The purpose of this study is to undertake an extensive re exa ....Parkinson's Disease is caused by injury to a group of brain cells called the Basal Ganglia. Our current ideas about how this part of the brain works is dominated by a well know theory. This theory requires that the output pathway of the basal ganglia to have a negative or inhibitory influence on its target. However there are numerous reasons why this would be unlikely, including some recent evidence from experiments in our laboratory. The purpose of this study is to undertake an extensive re examination of the output paths of the Basal Ganglia. If our suspicions are correct, it will lead to a review of the whole way in which we think the Basal Ganglia works.Read moreRead less
Motor Unit Synchronisation And Neuromuscular Performance
Funder
National Health and Medical Research Council
Funding Amount
$198,500.00
Summary
The fine control of force is important for many everyday tasks such as writing, grasping objects between index finger and thumb, and fastening buttons. Factors that influence the ability to control force include the coordinated activation of groups of muscle fibres called single motor units. This proposal focuses on the concept that the coordinated activation of motor units is influenced by muscle activity and can impair the ability to produce finely controlled muscle contractions. The goal of t ....The fine control of force is important for many everyday tasks such as writing, grasping objects between index finger and thumb, and fastening buttons. Factors that influence the ability to control force include the coordinated activation of groups of muscle fibres called single motor units. This proposal focuses on the concept that the coordinated activation of motor units is influenced by muscle activity and can impair the ability to produce finely controlled muscle contractions. The goal of these studies is to explore the boudary conditions of the adaptive nature of the nervous system to examine how coordinated motor unit activity influences these aspects of neuromuscular performance. The outcomes of these experiments will identify if altering muscle activity influences the control of movement by altering single motor unit activity. These results will have direct application to the interpretation of abnormal movement control and tremor that is observed in certain neurological diseases such as Parkinson's disease. Furthermore, new information will be gained on the adaptability of the motor system and its role in the execution of fine motor tasks that may aid in the development of rehabilitation strategies following stroke or spinal cord injury.Read moreRead less
The Regulation Of Pluripotency And Self-renewal In Embryonic And Germline Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$491,767.00
Summary
Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal ....Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal embryonic stem cells grown in culture could be used to replace the lost or disabled neurons in the patient. Many other conditions including diabetes, cystic fibrosis, myocardial infarction (heart attack) and stroke could potentially be treated with stem cell based therapies. Understanding the molecular regulators that govern establishment and maintenance in culture of stem cell lines derived from embryos and from germ cells is the primary goal of this study. We will use well-established techniques to genetically manipulate mouse embryonic stem cells and embryos to examine the role of a specific gene, NANOG. Named after the Celtic legend of Tir NaNog (land of the ever young). When NANOG was forced to remain active, embryonic stem cells were able to grow in media deficient in factors usually required for self-renewal and did not lose their pluripotency even when treated with chemical agents that usually induce differentiation. Understanding the full capacity of NANOG to influence stem cell self-renewal and elucidation of the underlying molecular pathways regulated by this gene will provide valuable insights into the establishment and manipulation of stem cell lines from embryonic and adult tissues.Read moreRead less
This study aims to identify naturally occurring genetic variations between men which modify the impact of testosterone, the major male hormone, on men's health and medical care. This study will examine new factors which determine how much any particular man may gain benefit from testosterone exposure such as in muscle and bone development as well as suffer detrimental effects on cardiovascular and prostate diseases. This may clarify some new aspects of how men's health is determined as well as d ....This study aims to identify naturally occurring genetic variations between men which modify the impact of testosterone, the major male hormone, on men's health and medical care. This study will examine new factors which determine how much any particular man may gain benefit from testosterone exposure such as in muscle and bone development as well as suffer detrimental effects on cardiovascular and prostate diseases. This may clarify some new aspects of how men's health is determined as well as developing new, customized medical treatments for men.Read moreRead less
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of motor neurons that leads to death within 5 years of first symptoms. The only proven causes of ALS are gene mutations. But known ALS genes only account for 2% of cases. We aim to investigate a newly identified gene that encodes a protein (TDP-43) that misfolds in the motor neurons of ALS cases. We have found TDP-43 mutations in ALS patients. This exciting finding offers a unique opportunity to understand how TDP-43 causes ALS
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less