Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
Retinoic Acid Receptor-related Orphan Receptors And The Regulation Of Metabolism:insights Into Diabetes And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$760,799.00
Summary
Nuclear receptors (NRs) function as hormone dependent DNA binding proteins important in sustaining human health, highlighted by the array of medicines that target these proteins for human well being. ROR alpha is one such protein that we have shown regulates fat mass, obesity, and glucose tolerance. Obesity and diabetes are often linked with inflammation. We will examine how ROR controls inflammation during metabolic disease.
Profiling Global Inflammatory Signatures For GPCRs In Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$687,770.00
Summary
Macrophages are important white blood cells of the immune system. They trigger inflammatory responses to infection or injury, but prolonged inflammatory responses can lead to chronic diseases. In this project we aim to better understand how macrophages sense the outside environment, how external signals trigger inflammatory processes, how this leads to diseases such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases, and how to control them with drugs.
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
The Structure And Function Of The Apical Domain In Insulin Secreting Beta Cells.
Funder
National Health and Medical Research Council
Funding Amount
$571,741.00
Summary
Loss of control of insulin secretion is causal in diabetes and therefore its understanding is a key goal to shed light on the disease. We have recently identified a new domain in the insulin secreting cells, called the apical domain. This proposal will define the role of this apical domain in controlling insulin secretion. The outcomes could provide new insights into how diabetes develops and new targets for therapies.
Spatial Organization Of Lck As A Regulatory Mechanism Of TCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$601,263.00
Summary
To function in an immune response, T cell become activated when the interactions between the T cell receptor and the kinase Lck on the cell surface results in intracellular signals. Here, we will investigate how the kinase is organized on the cell surface during receptor activation and what intrinsic and extrinsic parameters regulate its organization. The research is based on novel single molecule imaging tools and will provide new insights into the regulation of T cell activation.
Targetting The CIB1-sphingosine Kinase Interaction In Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$805,034.00
Summary
Sphingosine kinase is a protein involved in cancer development and progression. We have identified that the cancer-inducing activity of sphingosine kinase is controlled by another protein called CIB1 which itself appears involved in causing cancer by deregulating sphingosine kinase. In this study we will examine and target the interaction between sphingosine kinase and CIB1 as a potential therapeutic intervention in cancer.
Preventing Blindness: Blocking TGF¤-induced EMT And Cataract Development
Funder
National Health and Medical Research Council
Funding Amount
$343,824.00
Summary
Cataract, the loss of transparency of the eye lens, is a major cause of blindness. We have identified molecules in the lens important for maintenance of its transparency and plan to characterise their effectiveness in preventing cataract formation.
Understanding SOCS3 Inhibition Of JAK Activity In Myeloproliferative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The myeloproliferative disorders are diseases in which abnormal blood cell development leads to a risk of stroke, thrombosis, hemorrhage and leukemia. Remarkably, three of these disorders are caused by an error in a single enzyme that makes it over active. The enzyme, JAK2, controls how cells respond to hormone-like messengers called cytokines. We are investigating a cellular pathway that inhibits this enzyme in order to understand the progression and potential treatment of the disorders.