How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Dissemination And Virulence Properties Of The She Pathogenicity Island Of Shigella Flexneri.
Funder
National Health and Medical Research Council
Funding Amount
$110,625.00
Summary
Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry g ....Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.Read moreRead less
Genetic And Functional Analysis Of Brain Malformations
Funder
National Health and Medical Research Council
Funding Amount
$105,327.00
Summary
Disorders of early brain development are recognised as a significant cause of illness and disability in children. Unfortunately, the causes of these conditions are poorly understood, and treatment options are limited. It has become apparent that many of these conditions have an underlying genetic basis. This project will identify genes that regulate brain development and aid the development of improved treatment programs for brain and mind disorders.
Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
Reaction transition states of halide-cluster complexes via velocity-map imaging of photoelectrons. This study will investigate the transition point between the reactants and products of a chemical reaction using a novel photoelectron imaging technique, velocity-map imaging. It is this region of chemical reactions that is the least understood. By combining the use of weakly bound negatively charged clusters and laser photodetachment of these clusters, information can be gleaned about these transi ....Reaction transition states of halide-cluster complexes via velocity-map imaging of photoelectrons. This study will investigate the transition point between the reactants and products of a chemical reaction using a novel photoelectron imaging technique, velocity-map imaging. It is this region of chemical reactions that is the least understood. By combining the use of weakly bound negatively charged clusters and laser photodetachment of these clusters, information can be gleaned about these transition states. The technique will be applied to an important class of halide-cluster complexes that form a set of prototypical reactions. These species also play important roles ranging from ozone depletion through to industrial chemistry.Read moreRead less
Imaging chemical reaction dynamics from the transition state to reaction products. Chemical reactions play a key role in many atmospheric, environmental and industrial processes. An understanding of reactions at the molecular level will lead to significant economic benefits, through more efficient reaction control, and through the identification of the key environmental factors which influence why particular reactions proceed. Our study of chemical reaction dynamics has been driven by technolo ....Imaging chemical reaction dynamics from the transition state to reaction products. Chemical reactions play a key role in many atmospheric, environmental and industrial processes. An understanding of reactions at the molecular level will lead to significant economic benefits, through more efficient reaction control, and through the identification of the key environmental factors which influence why particular reactions proceed. Our study of chemical reaction dynamics has been driven by technological advances which enable key stages of a reaction to be imaged and studied at the molecular level. Read moreRead less
High-Throughput Discovery Of Synergistic Drug Combinations For Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,526,568.00
Summary
Treatment outcomes for patients with metastatic bowel cancer remain poor, with most tumours developing resistance within 24 months. A key problem is that cancers are genetically diverse, with some cells inevitably resistant to any given treatment. This study aims to discover effective drug combinations targeting distinct essential tumour cell functions through robotics-based pairwise testing of known drugs on bowel cancer cell lines representing the genetic diversity of the disease.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Targeting PI3K-regulated MicroRNAs To Treat Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$532,593.00
Summary
Current therapeutics largely delay heart failure progression rather than regressing it. New therapeutic strategies with the capability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.