Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place 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. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
I am a biochemist determining how metabolism is controlled in response to energy supply and demand. This is important in order to understanding how diet and exercise are beneficial to health.
Ciliary Neurotrophic Factor: A Novel Theraputic Agent For The Prevention Of Muscle Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$602,673.00
Summary
In 1995 leptin was discovered and scientists world-wide hoped that this was the great panacea in the treatment of obesity related disorders. Alas, from 1995-1997 the identification of a novel cytokine inducible compound termed suppressor of cytokine signaling (SOCS) that negatively regulated leptin signalling and lead to leptin resistance, quashing hopes for a viable anti-obesogenic drug. Recently, however, work from our group has demonstrated that the neuropoietic cytokine, ciliary neurotrophic ....In 1995 leptin was discovered and scientists world-wide hoped that this was the great panacea in the treatment of obesity related disorders. Alas, from 1995-1997 the identification of a novel cytokine inducible compound termed suppressor of cytokine signaling (SOCS) that negatively regulated leptin signalling and lead to leptin resistance, quashing hopes for a viable anti-obesogenic drug. Recently, however, work from our group has demonstrated that the neuropoietic cytokine, ciliary neurotrophic factor (CNTF), can act in an anti-obesogenic fashion in a manner similar to leptin. However, unlike leptin, when we place rodents on a high fat diet, the effects of CNTF persist and override induction SOCS proteins. This project will examine the biochemical pathways that allow the actions of CNTF to persist in the presence of diet-induced obesity. This is of major significance because in completing this work, the potential for the development of peripheral tissue drug targets for the treatment of obesity related diseases are both tangible and realistic.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.
The Role Of Protein Kinase C Epsilon In The Generation Of Lipid-Induced Insulin Resistance In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can in ....Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can interfere with the normal signalling of insulin. We have recently found that mice lacking an enzyme thought to be involved in such negative pathways are less susceptible to insulin resistance caused by high-fat feeding. The aim of this project is to investigate the mechanism by which this enzyme contributes to inhibition of insulin action. We will determine the step in normal insulin signalling which is blocked by the activation of the enzyme upon increased fat supply. This will help us to determine the pathway leading from the enzyme to insulin signalling. We will also identify the particular form of fat which leads to activation of the enzyme. This work will lead to a better understanding of the mechanisms by which fats can play a role in the generation of insulin resistance, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.Read moreRead less
Identifying The Critical Components Of Growth Factor-mediated Survival Pathways
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
The regulation of cell lifespan (cell survival) is controlled by growth factors and lies at the heart of all biological processes. However, little is known of the molecular switches inside cells that either turn survival on or off. We propose to identify and characterize the molecular switches inside cells that control the balance between cell survival and death. Targeting specific components of these switches may provide new approaches for the treatment of cancer and infectious diseases.