Neural Sensing Of Hunger Links Homeostatic And Reward Pathways
Funder
National Health and Medical Research Council
Funding Amount
$444,366.00
Summary
Cells in the brain that respond to signals of hunger also increase motivation to obtain food and there reward value of food. This proposal examines how these hunger cells, called AgRP cells, sense changes in metabolic state in order to increase motivation and food reward pathways. We believe that understanding this process may help us understand why obese individuals overeat foods high in sugar and fat.
Overcoming Barriers To Improved Physical Health In People With Severe Mental Illness
Funder
National Health and Medical Research Council
Funding Amount
$864,658.00
Summary
People with severe mental illness have high rates of cardiometabolic disease and reduced life-expectancy. Public intervention campaigns have had little impact on component risks (obesity, smoking, physical inactivity, poor nutrition). This study will determine factors associated with changes in cardiometabolic profiles in people with severe mental illness; examine impediments to risk modification; and develop targeted interventions for implementation within mental health services.
Deciphering The Metabolic And Endocrine Profile Of Healthy Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$563,194.00
Summary
Obesity is associated with the development of metabolic diseases, however, it is becoming clear that it is where the excess fat is stored that is more important when predicting the health risks associated with obesity. This project aims to identify whether adipocyte progenitor cells, which eventually become fat cells, are ‘preprogrammed’ and whether differences in these cells explain the generation of either healthy or unhealthy fat in different locations of the body.
Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.
Targeting Nicotinamide Adenine Dinucleotide Biosynthesis To Improve Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Nicotinamide adenine dinucleotide (NAD) is a cellular metabolite that regulates many biological processes. NAD levels decline with age and also in obesity and interventions that increase NAD levels produce favourable metabolic effects. In this proposal we will utilise a range of novel experimental models to define the molecular pathways that mediate the beneficial effects of NAD.
Transforming The Diagnosis Of Mitochondrial Disorders Using High-throughput Sequencing, Functional Prediction And Experimental Validation
Funder
National Health and Medical Research Council
Funding Amount
$670,794.00
Summary
The human genome project sparked enormous improvements in our ability to sequence DNA. “Next Generation” DNA sequencing can potentially sequence an individual’s entire genome in a week and has the ability to transform the diagnosis of inherited diseases but is as yet unproven in a medical genetics context. We will develop and validate the use of Next Generation sequencing to enable the rapid sequencing of over 1000 genes in which mutations cause inherited metabolic diseases.
How Does Exercise Ameliorate Programming Of Metabolic Dysfunction In Offspring Of Obese Mothers?
Funder
National Health and Medical Research Council
Funding Amount
$524,121.00
Summary
Obesity is a worldwide disease, reflecting an interaction between our environment (diet, physical activity) and genes. We know that a mother's unhealthy diet can predispose offspring to diabetes, and exercise can improve this, but the underlying mechanisms are poorly understood. Here we will examine how exercise can benefit offspring of obese mothers, and test a drug that mimics the effects of exercise. The proposed research will provide insight into ways of reducing the obesity epidemic.
Mechanism Of Action And Targeting Of Hexokinase II In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$643,607.00
Summary
Deaths from the brain cancer, glioblastoma, are as common as from the skin cancer in Australia. For most patients diagnosed with glioblastoma there is no realistic possibility of cure or even survival beyond a few years. We propose to understand and target glioblastomas aberrant metabolism of glucose, which may lead to better treatments for this devastating cancer.
Drug Targeting To Sites Of Lymph-adipose Interaction To Transform The Treatment Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$515,172.00
Summary
Insulin resistance (IR) underpins the development of inadequately treated heart and metabolic diseases such as type 2 diabetes. Recently we demonstrated that high fat diets promote increased leakage of fluid from lymph vessels to abdominal fat, and that increased access of lymph fluid to fat stimulates fat expansion and changes in fat function that promote IR. This project seeks to optimise novel drug delivery strategies that target lymph and fat and more effectively treat IR.
Regulation Of Metabolic Dysfunction And Exhaustion Of Virus-specific T Cells During Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$749,152.00
Summary
T cells control infections and cancer cells. During chronic infection or tumor development, however, loss of function of T cells prevents efficient clearing of pathogens or cancer cells, a phenomenon termed T cell ‘exhaustion’. We have found that the regulator protein IRF4 controls cellular nutrient usage, growth and function of T cells and that very amounts of IRF4 occur in T cells during chronic infection. We propose to examine the precise role of IRF4 in chronically stimulated T cells.