Identification Of Cardiac Sarcoplasmic Reticulum Targets For Cardiotoxic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$265,986.00
Summary
Anthracyclines are drugs which are used successfully in chemotherapy. Unfortunately, these drugs can lead to serious heart problems which sometimes result in death, and the mechanisms behind this remain elusive. Finding the specific targets of these drugs and how these drugs affect heart contraction may lead to designing drug cocktails which protect the heart from side effects.
Anthracyclines Disrupt Ca2+ Signalling In Cardiomyocytes: A Contribution To Cardiac Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$525,620.00
Summary
Anthracyclines are one of the most effective drugs used in chemotherapy, but cause side effects resulting in serious heart problems which can be fatal. The link between anthracycline therapy and the problems they cause in the heart is not fully defined. We will investigate mechanisms leading to these side effects and define specific targets of anthracyclines in the heart. It is hoped this will lead to the design of new drugs which counteract the side effects of anthracycline treatment.
Intracellular Calcium Signalling And Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,357.00
Summary
The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat mal ....The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulation of calcium in liver cells is abnormal. The aims of the present experiments are to investigate the mechanisms by which hormones regulate the flow of calcium into liver cells. The experiments will involve the measurement of calcium in different regions of liver cells using fluorescent dyes and high resolution microscopy, and the identification of structural proteins and organelles within the liver cell which are required to control calcium inflow. The results should show how an important type of calcium channel in liver cells works and is controlled. This knowledge will allow better treatment of diabetes, fat malabsorption and liver failure. The knowledge should also lead to improvements in liver transplant operations.Read moreRead less
The Putative Drug Metabolising Enzyme SULT4A1 Is A Sulfotransferase Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$467,851.00
Summary
The sulfotransferase SULT4A1 is a novel protein found predominantly in neurons but its function is unknown. This project will investigate the mechanisms that the body uses to regulate the levels of this protein and how it may interfere with other enzymes essential for metabolising hormones and neurotransmitters.
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
Peptide Toxins From Animal Venoms Specifically Targeting Voltage-gated Sodium Channels As Novel Analgesics And Pesticides
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This project aims to understand how certain animal toxins that cause analgesic and pesticidal effects in model animals interact with biological ion channels in atomistic detail using computational techniques. By understanding the detailed molecular interactions involved in the binding of the toxins to channels, toxin variants with improved potency and specificity may be designed as promising templates for novel analgesics and pesticides.
Alzheimer's, Huntington's and Parkinson's diseases involve the formation of protein aggregates, termed amyloid. The formation of amyloid leads to cell death and neurodegeneration. The most important cellular events perturbed by the formation of amyloid aggregates are unclear. Recent evidence suggests that sterols (including cholesterol) have an important role in cellular toxicity. This study will examine the molecular basis for this, enhancing our understanding of the amyloid diseases and could ....Alzheimer's, Huntington's and Parkinson's diseases involve the formation of protein aggregates, termed amyloid. The formation of amyloid leads to cell death and neurodegeneration. The most important cellular events perturbed by the formation of amyloid aggregates are unclear. Recent evidence suggests that sterols (including cholesterol) have an important role in cellular toxicity. This study will examine the molecular basis for this, enhancing our understanding of the amyloid diseases and could suggest novel therapeutic avenues.Read moreRead less