Testing Novel Therapies Using Paediatric Brain Tumour Models
Funder
National Health and Medical Research Council
Funding Amount
$384,023.00
Summary
Brain tumours are the second most common childhood cancer, with 300 children affected in Australia each year. Many children with brain tumours continue to die of their disease, whilst survivors are often left with devastating life long side effects. Our goals are to harness the power of innovative model systems of childhood brain tumours, in order to test the effectiveness of new treatments for these devastating diseases, so that the most promising therapies can be taken through to the clinic.
Food allergies have emerged as a major public health concern affecting 1 in 10 Australian infants. Hospitals waiting times are in excess of 12-months for specialist services. Recent changes in the environment are driving up rates of food allergy but the mechanisms are unclear. Epigenetics is the science of how the environment influences gene behaviour. This fellowship will address the important and urgent question of how modern environments are changing our genes, leading to food allergy.
Mature red cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. We will determine the role of several molecules that interact with Lyn including Cbp, Liar and LACM, towards apects of red blood cell development.
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.
Leukaemia-cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of these is augmented activity of enzymes called tyrosine kinases including members of the Src family. One called Lyn has been implicated in several leukaemias as well as cancer. We have identified a novel mechanism of down-regulating this family of enzymes mediated by small proteins. These may allow us to develop novel therapeutics for cancer-leukaemia treatment.
The Importance Of Neutrophil Plasticity In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Lung disease is a lifelong problem for people with cystic fibrosis (CF). Blood immune cells called neutrophils swarm the lung and cause ongoing damage. No treatments exist because how CF lungs talk to neutrophils is poorly understood. I will apply new skills from an international neutrophil expert to study samples from AREST CF, a world leading CF research group. This unique combination will recreate the early CF lung in the laboratory, testing triggers of CF lung disease and potential drugs.
Epithelial Drivers Of Neutrophil Plasticity In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$849,462.00
Summary
Why airway inflammation becomes chronic so early in life for people with cystic fibrosis (CF) is unclear. This project will use the latest techniques to characterise immune cells found in airways of infants with CF and model in the laboratory how immune cells react to the CF airway. We will challenge CF airway cells with different bugs that can infect the lung, then see if the responses by CF airway cells can change the normal response of immune cells, triggering chronic disease.
Restoration Of Diabetes Associated Cognitive Deficits Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$430,998.00
Summary
Diabetes is known to increase the risk of dementia. Although the mechanisms are currently unknown, a recently emerging body of evidence suggest that damaged blood vessels of the brain may be central to onset and progress of cognitive dysfunction. Consistently, the dysfunction of brain blood vessels is often observed in the brain of diabetes subjects. Therefore, this project will investigate whether the amelioration of disrupted brain blood vessels restores the cognitive function in diabetes.
Dementia Associated To Diabetes: Prevention Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$719,770.00
Summary
Diabetic insulin resistance is reported to induce cognitive decline and dementia. An accumulating body of evidence suggest that compromised integrity of neurovascular unit and following changes in cerebral lipid homeostasis may be centrally involved in the neurodegeneration and cognitive deficits. Therefore, the project aims to prevent the insulin resistance-associated cognitive impairment by modulating the integrity of cerebrovasculature and lipid homeostasis.
Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.