Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypothesis that this pacemaker mechanism is also fundamental to heart pacemaking and conduction. Positive support for our hypothesis, as indicated by our pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
The Role Of Antibody In Inflammatory Demyelinating Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$218,566.00
Summary
The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antib ....The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antibodies bind to specific target molecules and our work is close to identifying that target on nerve. We also plan to study how antibody leaks into nerve. This knowledge should allow more specific and effective treatment to be developed.Read moreRead less
Contribution Of Tumour And Stroma Derived Cysteine Cathepsins To Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$447,094.00
Summary
Breast cancer is a serious clinical problem once the disease spreads to distant tissues such as lung and bone. We have identified a group of genes called the cysteine cathepsin proteases that have increased activity in breast cancers that spread to bone and we have shown this in a mouse model and also in human cancer. We will investigate the contribution of these genes to invasion and test whether inhibiting specific cathepsins can prevent spread of breast cancer to bone in our mouse model .
Inhibition Of Breast Cancer Metastasis Through Targeting Of Laminin-10 Function
Funder
National Health and Medical Research Council
Funding Amount
$391,241.00
Summary
Breast cancer affects 1 in 11 women in Australia. Whilst breast cancer is highly curable when detected early, current treatments are ineffective when the disease has spread to other organs such as bone and lungs. Thus, novel therapies for the treatment of advance disease are urgently needed. We have found that laminin-10, a protein present in the breast and thought to control normal breast development and maturation, is particularly abundant in aggressive tumours as well as in those that have sp ....Breast cancer affects 1 in 11 women in Australia. Whilst breast cancer is highly curable when detected early, current treatments are ineffective when the disease has spread to other organs such as bone and lungs. Thus, novel therapies for the treatment of advance disease are urgently needed. We have found that laminin-10, a protein present in the breast and thought to control normal breast development and maturation, is particularly abundant in aggressive tumours as well as in those that have spread to bone and lungs suggesting that this protein may play a role in the dissemination of breast cancer cells to other organs. Consistent with this, we have found that laminin-10 stimulates breast tumour cell adhesion and movement in culture, two activities required for successful metastasis of tumour cells. The overall objective of the projects is to demonstrate that breast cancer metastasis can be inhibited by interefering with the function of laminin-10. To this end, we will measure the effect of blocking the production of LN-10 in breast tumour cells on their ability to metastasise. Alternatively, we will test fragments of laminin-10 for their ability to block laminin-10-induced tumour cell growth and movement (required for their escape from the breast) and viability (required for their establishment in distant organs). We will generate antibodies against the most inhibitory fragments and test their effect on spontaneous metastasis in a clinically relevant mouse model of breast cancer metastasis in an attempt to stop-reverse the progression of the disease. If successful, this project will provide the foundation for the development novel inhibitors targeting laminin-10 for the treatment of patients with advanced breast cancer.Read moreRead less
Does Maternal Supplementation With N-3 Long-chain PUFA In Pregnancy Influence Cognitive Development In Childhood?
Funder
National Health and Medical Research Council
Funding Amount
$552,676.00
Summary
During pregnancy, omega-3 fats (like those in fish) are deposited in the brain of the developing baby. Women get these fats from the diet but Australian women typically eat a diet low in fish. Because research has linked high fish intake in pregnancy with better IQ in children, omega-3 oils are included in some pregnancy supplements. However their effect on child development is not clear. This project will test whether taking fish oil while pregnant improves a child's IQ.