Protein tyrosine phosphatases (PTPs) control cell communication networks referred to as cellular signaling. This proposal is focused on understanding the roles of PTPs in cellular signaling networks perturbed in human disease & delineating novel opportunities for therapeutic intervention
Characterization Of A Novel IFNbeta Signaling Axis Mediated Via IFNAR1
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
Type I interferons (IFNs) play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. This project will investigate a novel IFN signaling axis that we have recently characterized that is mediated via the low affinity IFN receptor, IFNAR1. This signaling axis occurs independently of the high affinity IFN receptor IFNAR2 and contributes to lethality in a model of septic shock.
Targeting Cytokine Signalling In Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$917,626.00
Summary
Systemic lupus erythematosus is a disease where the immune system attacks normally healthy tissues. The spontaneous overproduction of signalling molecules called interferons in lupus plays an important role in the severity of the disease. We have found that two proteins, named Bcl6 and PLZF, are important in controlling the interferon response in lupus patients. We propose that identifying how these proteins act to control interferon will aid in developing new treatments for lupus.
Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related di ....Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related disease.Read moreRead less
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.
Role Of Sphingolipid Signalling In Hepatic Insulin Resistance And Its Application In Prediction Of Risk For Type 2 Diabetes And Prediabetes
Funder
National Health and Medical Research Council
Funding Amount
$563,305.00
Summary
Type 2 diabetes is expected to reach epidemic proportions in the coming decades. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. We have identified an enzyme that plays an important role in insulin signalling. The possibility is that the level or activity of this enzyme is a potential biomarker of the prediabetes state and could be also used as a target
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.
An AMPK Myristoyl Switch Controls AMP Mediated Metabolic Stress Signaling
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project is investigating an enzyme called AMP-activated protein kinase that plays a pivotal role in controlling how our bodies regulate energy metabolism in response to exercise and diet. Improved understanding of how this enzyme is regulated may provide new therapeutic methods for mimicking the beneficial effects of diet and exercise to treat multiple metabolic diseases including obesity, Type 2 diabetes and cardiovascular disease.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which fu ....Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Building on recent breakthroughs made at St. Vincent's Institute, this project will produce innovative research into novel mechanisms that control AMPK. These discoveries will greatly increase our understanding of AMPK regulation by cellular processes, and aid the design of more effective AMPK drugs.Read moreRead less