A Longitudinal Study Of Knee Osteoarthritis Using X-ray And Magnetic Resonance Imaging
Funder
National Health and Medical Research Council
Funding Amount
$861,925.00
Summary
Osteoarthritis is the most common form of arthritis and commonly affects the hand hip and knee in older Australians with an annual cost of around 4 billion dollars. This study will lead to a greater understanding of the role of factors influencing the development and progression of osteoarthritis of the knee by utilising a novel magnetic resonance imaging technique. In particular, it will focus on the role of physical activity and bone underlying the cartilage. If associations are discovered, ac ....Osteoarthritis is the most common form of arthritis and commonly affects the hand hip and knee in older Australians with an annual cost of around 4 billion dollars. This study will lead to a greater understanding of the role of factors influencing the development and progression of osteoarthritis of the knee by utilising a novel magnetic resonance imaging technique. In particular, it will focus on the role of physical activity and bone underlying the cartilage. If associations are discovered, accurate public health messages regarding prevention can then be developed.Read moreRead less
LMO2-containing Complexes In Leukemia And Blood Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$803,652.00
Summary
Childhood T-cell leukemias have a poor prognosis for recovery. We are determining, with atomic level precision, how the proteins Lmo2 (also linked to prostate and other cancers) and Tal1, and their binding partners contribute to both normal blood cell development and T-cell leukemia. With this information we are developing reagents that can be used to disrupt disease-causing complexes, and which will lead towards the development of new, specific, therapeutics for leukemias and other cancers.
A Structural Investigation Into The T-cell Response To Epstein Barr Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$549,000.00
Summary
X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as ....X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as binding to other proteins, acting as an enzyme or interacting with nucleic acids. To determine how a protein acts, it is vital to know the precise three-dimensional shape at the atomic level. This proposal is concerned with understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. Epstein Barr Virus is an ubiquitous human pathogen that has being linked to a number of cancers. This work will further our understanding of the immune response to Epstein Barr Virus.Read moreRead less
Structural And Diffusion Tensor Neuroimaging In Twins Concordant And Discordant For Psychosis.
Funder
National Health and Medical Research Council
Funding Amount
$477,375.00
Summary
Measures from specialised brain scans i.e. MRI's (Magnetic Resonance Imaging) have suggested that several areas in the brain are different in those individuals who suffer from psychosis compared to those who don't. Evaluations of these brain differences have helped us better understand the nature of these illnesses. For example, frontal lobe dysfunction has been linked with the loss of ability to plan and organize information, seen in those who have schizophrenia. These measures may also help cl ....Measures from specialised brain scans i.e. MRI's (Magnetic Resonance Imaging) have suggested that several areas in the brain are different in those individuals who suffer from psychosis compared to those who don't. Evaluations of these brain differences have helped us better understand the nature of these illnesses. For example, frontal lobe dysfunction has been linked with the loss of ability to plan and organize information, seen in those who have schizophrenia. These measures may also help clarify the relationship between the genetic and environmental factors contributing to the development of these disorders. One of the best ways to investigate this relationship is the use of a twin study design. The Australian study of twins with psychosis will recruit dizygotic (DZ) and monozygotic (MZ) twin pairs in which at least one twin is affected by a psychotic disorder, plus control twin pairs matched for age, sex and zygosity. Measures derived from MRI scans will be collected in an attempt to further define specific brain regions reported to be different in psychosis. In addition Diffusion Tensor Imaging (DTI) will be used to visualize white matter tracts in the brain. The twin study design will allow us to differentiate genetic and environmental factors associated with these brain measures and help evaluate the potential for these measures to genetically define sub-groups of individuals with psychotic disorders. The identification of these subgroups would facilitate the search for susceptibility genes. Additionally, this study will help clarify the possible clinical overlap between affective (i.e. bipolar affective disorder) and non-affective (i.e. schizophrenia) psychotic disorders. The information obtained from this study has the potential to greatly improve our understanding of caustive factors in psychosis, which may also lead to earlier diagnosis and treatment, thereby improving prognosis.Read moreRead less
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.
Integrons, Mobile Gene Cassettes And Pathogencity In Vibrio Cholerae
Funder
National Health and Medical Research Council
Funding Amount
$550,285.00
Summary
Bacteria are remarkably adaptive and evolve in ways that plants and animals do not. One of these ways is Lateral Gene Transfer or LGT, which is a process allowing bacterial cells to share genes. Such mobile genes can greatly influence the extent to which pathogenic bacteria can cause disease. One notable example is Vibrio cholerae where many strains can be benign but some can give rise to cholera pandemics. Here, we will investigate this phenomenon in this important bacterium.
Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and ....Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and cellular events associated with periodontal regeneration. Despite efforts to induce regeneration through the selective use of growth and differentiation factors it is becoming obvious that the most significant factor in successful clinical outcomes is the recruitment of special cells to the site of damage which have the potential to repair tissue damage. Thus, we intend to engineer different types of periodontal matrices in the laboratory and then transplant these newly formed tissues into sites affected by periodontal disease in an attempt to repair the damage caused by the disease process.Read moreRead less
Signalling Pathways Activated By Atrial Dilatation And Their Relationship To Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$449,878.00
Summary
Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4 ....Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and its immediate precursor phosphatidylinositol(4,5)bisphosphate (PIP2) in atrial fibrillation with a view to providing targets for therapy that are well tolerated. There is recent evidence that Ins(1,4,5)P3 and PIP2 can contribute to atrial fibrillation. Over the next 3 years we will study cellular signalling responses to acute and chronic dilatation of the atria and examine the relationship of these findings to clinical atrial fibrillation. We will identify the G protein and phospholipase C subtypes involved in responses to stretch and use tools developed in these studies in experiments with atrial fibrillation models.Read moreRead less
Developing Inhibitors Of An Essential Histidine Kinase In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
Staphylococcus aureus (Golden staph) has been termed a "superbug" because of its persistent ability to acquire resistance to a wide range of antibiotics. Once considered primarily a hospital-acquired pathogen, many patients are now being infected with antibiotic-resistant Golden staph outside of hospitals. The primary aim of this research program is to develop new antibiotics to treat antibiotic-resistant strains of Staphylococcus aureus and related pathogens.