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
How do nutrient-regulated changes in mitochondrial protein acetylation and sirtuin activity affect mitochondrial function and insulin action? Lysine acetylation affects the function of many proteins. This project will examine how excess nutrient availability and altered sirtuin activity affects the acetylation state and function of mitochondrial proteins. This information may identify therapeutic targets to treat diseases associated with mitochondrial dysfunction.
Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
Endocrine signalling from bone cells in the regulation of glucose and energy homeostasis. Osteoporosis, obesity and diabetes are increasingly common, all of which are in urgent need of more effective therapies. This project examines powerful neuropeptide signalling pathways that integrate bone homeostasis with whole body energy and glucose balance. Initial studies have defined the efferent hypothalamic pathways of this system and this project will build upon these findings to examine the feedbac ....Endocrine signalling from bone cells in the regulation of glucose and energy homeostasis. Osteoporosis, obesity and diabetes are increasingly common, all of which are in urgent need of more effective therapies. This project examines powerful neuropeptide signalling pathways that integrate bone homeostasis with whole body energy and glucose balance. Initial studies have defined the efferent hypothalamic pathways of this system and this project will build upon these findings to examine the feedback signals produced by bone cells to regulate adipose and pancreatic function. Exploring this entirely new paradigm of skeletal biology, will reveal novel circulating factors capable of regulating adipose and glucose economies, as well as bone mass, thereby offering potential therapies for these debilitating conditions.Read moreRead less