The Molecular Mechanism Of Ion-coupled Transport In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$441,407.00
Summary
Cells in the brain communicate through chemical signals called neurotransmitters. Neurotransmitter transporters reside in the membranes of cells and are responsible for regulating levels of these chemicals in the brain. They play an important role in the normal function of the human brain but their dysfunction is responsible for many diseases including Alzheimer's disease and motor neuron disease. It is crucial to understand how these proteins work in both normal and disease states.
N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$981,789.00
Summary
Many patients with schizophrenia remain treatment resistant even after “last resort” medications like clozapine. This proposal will conduct a novel multi-site randomised placebo controlled trial of adjunctive N-acetyl cysteine in patients with clozapine resistant schizophrenia. Treatment efficacy will be examined at 8, 26 and 52 weeks.
Roles of the kynurenine pathway in physiological and pathological brain function. This project will aim to study the metabolism of the essential amino acid tryptophan in the brain and its involvement in diseases including multiple sclerosis and brain tumours.
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.
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100985
Funder
Australian Research Council
Funding Amount
$409,574.00
Summary
Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes wit ....Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes with high efficacy and specificity. This project will provide new and intriguing insights into cellar function, with broad applications in basic research and biotechnology.Read moreRead less
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.Read moreRead less
A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability ....A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability of current drugs and thus significantly shorten the recurrence period. Such new drugs may have broad applicability.Read moreRead less
The Chemistry and Biochemistry of Chromium: Cancer and Nutrition. Of all of the human carcinogens, chromium(VI) has the highest level of occupational exposure, and is of increasing concern as an environmental carcinogen, as highlighted by the film Erin Brockovitch. Similarly, chromium(III) nutritional supplement consumption by humans and animals is rising rapidly, despite mounting concerns about their cancer risks. However, the complexity of Cr biochemistry is such that it is still poorly unde ....The Chemistry and Biochemistry of Chromium: Cancer and Nutrition. Of all of the human carcinogens, chromium(VI) has the highest level of occupational exposure, and is of increasing concern as an environmental carcinogen, as highlighted by the film Erin Brockovitch. Similarly, chromium(III) nutritional supplement consumption by humans and animals is rising rapidly, despite mounting concerns about their cancer risks. However, the complexity of Cr biochemistry is such that it is still poorly understood. This project aims at providing new insights into Cr biochemistry that are of relevance in evaluating risk factors for occupational and environmental exposure and for producing safer Cr dietary supplements.Read moreRead less