Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.
Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe ....Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe the fundamental process of cell differentiation in the central nervous system.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. Read moreRead less
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.Read moreRead less
Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Austra ....Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Australian patients, use novel techniques to identify biomarkers for IFNb response, evaluate the diagnostic and therapeutic value of the biomarkers, and develop a new test for NABs. Tailored use of this drug, and possible new therapeutic targets, will result, benefiting the patient and community.Read moreRead less