Stem cell to differentiation occurs in a bi-directional fashion. Dedifferentiation which allows specialized cells to become stem cells has been found to be important in both cancer and regeneration. In this proposal, we will investigate the metabolic reprogramming of neuronal dedifferentiation. The findings from this study will better inform us on how to specifically target tumours that arise from dedifferentiation.
I am a neuroscientist, who studies the neural mechanisms responsible for the control of human voluntary movements. My research is aimed at characterising the physiological mechanisms which are responsible for plasticity of the human motor cortical regions
Biomathematical Analysis Of Cell Invasion: Migration Of Neural Crest Cells To Form The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$449,484.00
Summary
Extending scientific studies to a mathematical level is the way to produce deep understanding and control. Mathematics has been applied less to biology, particularly the biology of development, than to other branches of science, no doubt due to the innate complexity and technical difficulties of seeing and measuring what is actually going on. Labelling, imaging and computational tools to visualise biological processes are only now becoming available. To build our bodies during embryonic developm ....Extending scientific studies to a mathematical level is the way to produce deep understanding and control. Mathematics has been applied less to biology, particularly the biology of development, than to other branches of science, no doubt due to the innate complexity and technical difficulties of seeing and measuring what is actually going on. Labelling, imaging and computational tools to visualise biological processes are only now becoming available. To build our bodies during embryonic development, cells must move; this is called cell migration. The same process occurs throughout life in wound repair. Uncontrolled migration is the hallmark of malignant cancers, where it is called invasion. The molecular mechanisms in cells that allow them to move are just beginning to be understood. However, the big questions determining the general rules of migration are more difficult to approach. Here are some examples of such questions. When to migrate? Where to migrate to? Which pathways? How many cells to migrate? How far? How fast? How to stop? Such simple questions are still unanswered. We are pioneering a novel and unique approach combining imaging of real cells migrating in real tissues (digital time-lapse movies) with mathematical modelling to understand the driving forces of cell migration-invasion. This technology is here applied to a particular example of cell migration where precursor nerve cells migrate all the way along the length of the gastro-intestinal tract in early development. This process gives rise to fatal birth defects associated with migration failure. The development of the nervous system in the gut has features in common with all other migrations and invasions, normal and pathological. A much more profound knowledge of the big picture of the developmentally and clinically crucial process of cell migration-invasion will emerge from this marriage of biological experimentation and mathematical modelling.Read moreRead less
Activity In Central Cough Networks In Patients With Cough Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Excessive cough associated with an airways disease represents the most common reason for doctor consultations. However, the current therapeutic options for relieving excessive cough are limited. This proposal will provide unprecedented insights into the brain mechanisms that contribute to the development of cough disorders in airways disease.
Role Of Load Detection And Compensation In Pathogenesis Of Obstructive Sleep Apnea.
Funder
National Health and Medical Research Council
Funding Amount
$340,867.00
Summary
This proposal will use novel techniques to explore how defective responses to the threat posed by a collapsing upper airway contribute to the Obstructive Sleep Apnea syndrome, a disease involving repetitive collapse of the upper airway in sleep. Responses to small increases in the resistance to inspiratory airflow will be examined by measuring the small electrcal responses in the brain to these loads, and the response of the muscles responsible for maintaining airway patency to the collapsing fo ....This proposal will use novel techniques to explore how defective responses to the threat posed by a collapsing upper airway contribute to the Obstructive Sleep Apnea syndrome, a disease involving repetitive collapse of the upper airway in sleep. Responses to small increases in the resistance to inspiratory airflow will be examined by measuring the small electrcal responses in the brain to these loads, and the response of the muscles responsible for maintaining airway patency to the collapsing forces induced by these loads, in both wakefulness and sleep. The brain's response to resistive loads will also be evaluated using the techique of functional magnetic resonance imaging, which demonstrates areas of the brain activated by a stimulus.Read moreRead less
Identification Of Novel Regulatory Factors In Midbrain Development To Improve Cell Therapies For The Treatment Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Cell transplantation is one of the most promising therapeutic strategies for the treatment of Parkinson’s disease. Cells are transplanted directly into the brain of the patient and can compensate for those lost to the disease. In this project we are identifying new genes that regulate the normal development of the transplanted cells in mice. We hope to use this knowledge to improve the reliability and effectiveness of the approach, bringing the therapy closer to the clinic.
Dissecting The Molecular Mechanisms Driving Cell Migration During Neurulation Triggered By The Netrin Receptor, Neogenin
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex pr ....In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex process in which early neural cells migrate toward the midline of the embryo and subsequently coalesce. This project seeks to determine the function of one molecular signaling pathway (the neogenin pathway) that has been implicated in driving these cell migration events. We will initially use the frog, Xenopus laevis, as our embryonic model since the developmental processes that form the Xenopus neural tube closely parallel those ocurring in the human embryo. This model will allow us to identify the molecules in the neogenin signaling pathway. We will also create mice that carry a mutation in the neogenin gene so that we can study neogenin function in the mammal. We anticipate that these studies will provide important insights into the development of the central nervous system and also into the aberrant molecular processes underlying neural tube defects in man.Read moreRead less