Epigenomic Profiling At Single Nucleotide Resolution In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$364,324.00
Summary
Epigenetics literally means 'above DNA' and refers to genetic marks that control how genes are turned on and off. The first part of this project will examine these marks on a whole genome level in normal human white blood cell development. This will identify new genomic regions involved in immunity. In the second part of the project the same technology will be applied to study paediatric cancer in Australia. This has the potential to identify new diagnostic marks and targets for treatment.
Immune Modifying Particles - A Novel Therapeutic Strategy To Treat West Nile Virus Encephalitis
Funder
National Health and Medical Research Council
Funding Amount
$550,926.00
Summary
The outcome of viral infection of the brain is determined by the attraction of white blood cells, especially monocytes into the brain. Monocytes have a paradoxical role during brain inflammation. On one hand they are essential defenders against viral infection. On the other they may cause lethal brain damage. This project aims to define the mechanism(s) through which a novel therapeutic strategy, known as immune modifying particles, can modulate monocytes migration and function during brain infe ....The outcome of viral infection of the brain is determined by the attraction of white blood cells, especially monocytes into the brain. Monocytes have a paradoxical role during brain inflammation. On one hand they are essential defenders against viral infection. On the other they may cause lethal brain damage. This project aims to define the mechanism(s) through which a novel therapeutic strategy, known as immune modifying particles, can modulate monocytes migration and function during brain infection.Read moreRead less
Role Of Bone-associated Macrophages In Bone Remodelling And Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$564,963.00
Summary
Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently inadequate. Consequently, there is a high demand for effective tr ....Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently inadequate. Consequently, there is a high demand for effective treatment options. This project grant application proposes a novel line of scientific investigation that will provide greater understanding of the contribution of macrophages (a cell type that has important roles in normal tissue maintenance and defense against infection) in bone remodelling and disease. Bone is continuously remodelled and replaced to maintain skeletal strength and mineral metabolism. We have shown that a population of macrophages is intimately associated with bone and propose that these cells play an important part in regulating bone remodelling. Macrophages have been implicated in many diseases that have damaging consequences on bone, including osteoporosis and several forms of arthritis, linking aberrant macrophage function to disease-associated bone damage. This project aims to characterize this population of bone-associated macrophages and determine their ability to influence the function of other cells integrally involved in bone remodelling. We will also undertake studies in animal models to determine whether these cells are required for bone remodelling and-or damage. Detailed description of the novel role of macrophages in bone biology will facilitate the development of superior therapeutics, preventatives and cures for bone diseases.Read moreRead less
THE INTERFACE BETWEEN INNATE AND ADAPTIVE IMMUNITY
Funder
National Health and Medical Research Council
Funding Amount
$4,905,420.00
Summary
Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in t ....Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in the laboratory with clinical investigation and analysis of human tissue. Understanding these processes will translate into better treatments for patients suffering from life-threatening allergy and asthma.Read moreRead less
Haematopoiesis, Metabolic Disorders And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Dr. Murphy’s work is centred on examining how different diseases such as obesity, diabetes and other inflammatory conditions increase people’s risk of heart disease. He will explore how these various inflammatory diseases influence the produce increased levels of white blood cells, which is important as increased white blood cells are positively associated with disease severity. He will also explore the relationship between blood cancers, know as leukaemia and how obesity.
S100A8/A9 As A Target In Metabolic Diseases To Inhibit The Acceleration Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$554,990.00
Summary
Obesity and diabetes are the leading cause of premature death, due to accelerated cardiovascular disease (CVD). The abundance of blood monocytes influences the progression and regression of CVD. We discovered that S100A8/A9 promotes monocyte production in obesity and diabetes. This project will explore how S100A8/A9 is produced in diabetes and obesity and if blocking its function using a novel drug will prevent obesity and diabetes associated CVD.
Origin Of Cells In The 'artificial' Artery Grown In The Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the s ....Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the structure of the surrounding tissue and the myofibroblasts differentiate further into functional smooth muscle. This raises the question: what is the origin of the cells of the capsule? Our previous studies suggested that monocyte-macrophages stimulated to enter the abdominal cavity in response to the sterile foreign body might be the source of the cells. In the current study we will use transgenic (c-fms EGFP and c-fms Cre Z-AP) mice in which cells of monocyte-macrophage lineage are genetically labelled. These cells can be clearly distinguished from all other cells of the body, and analysis of capsules formed around foreign bodies will give us a definitive answer. We will using micro-array analysis, determine which growth factors-cytokines are important in regulating differentiation of the cells, and the role of physical factors (eg pulsatile stretching). Finally, we will determine whether these cells stimulated to enter the abdominal cavity are capable of differentiating along alternative pathways, such as cardiac muscle or liver cells. Knowledge gained will further the use of the abdominal cavity as a bioreactor in which to engineer tissues for organ replacement therapies. Identification of the mechanisms regulating the (trans)differentiation and biology of the cells may also assist in wound repair strategies to prevent pathologies caused by excessive myofibroblast accumulation and fibrosis.Read moreRead less