Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the divers ....Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the diversity of cell types in our bodies. Enhancer regions interact with proximal promoters to regulate gene expression level and tissue-specificity. This project aims to develop transcriptional regulatory network models using high throughput chromatin interaction data and expression perturbation to link promoter and enhancers genome-wide.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
A tale of two genomes: integrating mitochondrial biogenesis into the cell cycle and metabolic control. The human genome is cordoned into two distinct compartments in our cells. Most genes are in the nucleus, while a distinct set of genes are held within our mitochondria. Using yeast as a model organism, this project will provide a holistic view of how expression of the two genomes is coordinated.
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
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five deca ....Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five decades. Low titres and frequent batch failures greatly affect capital use and represent a significant cost. In addition, current optimisation approaches are limited by the use of expensive and noisy endpoint assays. This project aims to use high-throughput chemistry (multi-omics) that overcome these limitations.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
The development of mass spectrometry techniques for mapping post-translational modifications in the wheat pathogen Stagonospora nodorum. The fungus Stagonospora nodorum is a significant pathogen of wheat causing in excess of $100 million dollars in yield losses per annum in Australia. This project will develop new analytical methods that can be used to detect important protein modifications in Stagonospora nodorum with the goal of securing Australia's wheat supply.
Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.