Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
The Role Of The AMPK-ACC2 Signaling Axis In Metabolic Control During Exercise And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$540,973.00
Summary
Australian society is experiencing an epidemic of obesity that is contributing to diabetes, cardiovascular disease and premature death. This project is investigating how exercise might prevent obesity and type 2 diabetes by examining the major pathways that regulate fat metabolism.
Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pa ....Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pathogen and mitochondrial biology and advanced cell biology tools. With most of the effector proteins yet to be characterised, benefits from the project will be to reveal specifically how these target mitochondria, and more broadly, how bacterial pathogens manipulate organelles for their survival.Read moreRead less
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by ....Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by FOXO proteins. Although very basic in nature, these projects will identify how FOXO proteins regulate muscle cell building and wasting and, therefore, present a potential therapeutic target for muscle wasting diseases, making this project highly significant.Read moreRead less
The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of ....The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of cellular networks in higher organisms such as cell polarisation, directed migration, metabolism and autophagy. Vertebrates have evolved mechanisms for joining individual Golgi stacks into a ribbon structure. The relevance of this ribbon structure remains a mystery. The project aims to answer this major question in cell biology.Read moreRead less
Impact Of Advanced Glycation On Anti-atherogenic Properties Of High Density Lipoprotein
Funder
National Health and Medical Research Council
Funding Amount
$372,471.00
Summary
Type 2 diabetes is a rapidly growing medical problem in Australia and around the world. Diabetes affects human health through its complications and the cardiovascular complications are a cause for major concern. One of the complications is the effect on plasma lipids: it makes cholesterol carrying particles to accumulate in the blood vessels, causing atherosclerosis. We intend to investigate how diabetes modify these particles making them atherogenic.
Regulation Of Lipid Metabolism By AMP Activated Protein Kinase
Funder
National Health and Medical Research Council
Funding Amount
$478,776.00
Summary
Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines ....Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.Read moreRead less
Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and ....Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and function of the AMPK. This work may provide important opportunities for drug design, understanding the impact of metabolism and ageing as well as increasing our knowledge of signalling pathways that control cellular events.Read moreRead less