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Unravelling Mechanotransduction Pathways In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$949,956.00
Summary
This project addresses the still unresolved question of involvement of mechanosensitive ion channels in heart hypertrophy and arrhythmias including ventricular arrhythmias. These pathological conditions are a cause of a broadening fiscal healthcare burden in Western societies. Consequently, investigating the role of this class of ion channels in heart disease presents a priority for medical science and a great opportunity to improve the health outcomes for the Australian people.
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less
Control Of Uterine Contraction: Role Of Interstitial Cells
Funder
National Health and Medical Research Council
Funding Amount
$587,206.00
Summary
Being born premature may increase risk of below average IQ, poor performance at school and behavioural difficulties in the child, and increased obesity and blood pressure as an adult, predisposing to life long socio-economic disadvantage. We have come up with a new approach to understanding the control of uterine contraction, namely, that cells other than muscle cells, recently identified in the uterine wall, are essential for inducing forceful and orderly muscle cell contraction during labour.
STIM1 And Orai1 Proteins In Store-operated Calcium Entry In Liver
Funder
National Health and Medical Research Council
Funding Amount
$516,552.00
Summary
The liver plays a central role in controlling vital functions of the body. Changes in calcium level in the liver cells regulate most their functions, including fat and carbohydrate metabolism. There is ample evidence that suggests that diseases such as fatty liver and cholestasis affect the control of calcium in the liver. This research will investigate the mechanisms of calcium homeostasis in the liver and provide information for development of new approaches for treating liver disease.
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.
Calcium acts as a signal to control cell processes important in cancer. The entry of calcium into the cell is regulated by calcium channels and we have found some channels are over-expressed in breast cancer. Altering the expression and activity of these calcium channels is a possible therapeutic approach for cancer. We will determine the reasons and consequences of alterations of calcium channels in breast cancer and whether they are viable anti-cancer therapies and biomarkers.
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.
Identifying And Exploiting Novel Pharmacological Targets For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancers are made up of different types of cancer cells, and not all cells contribute equally. A subset of cancer cells may be uniquely capable of driving tumor growth, rebuilding fatal tumors after therapy and establishing new tumors at distant sites. Identifying and exploiting the pathways that regulate the activity and survival of these cells will lead to better modes of treatment, and move towards a relapse-free future for breast cancer patients.