Investigating The Role Of Mitochondrial Tom40 In Regulated Cell Death And Neurodegeneration.
Funder
National Health and Medical Research Council
Funding Amount
$972,660.00
Summary
Mitochondria are internal compartments of cells, separated by bounding membranes. They are crucial to the life and death of cells, and to quality of human life and ageing. Diseases of the nervous system can be caused when mitochondria do not function properly. Our aim is to discover why a protein complex called TOM embedded in the bounding membrane is linked to dementia in some people. This will also lead to a better general understanding of the connection between mitochondria and human health.
Targeting Neurovascular Communication As A Novel Way Of Reducing Vision Loss In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$986,663.00
Summary
Diabetes is a leading cause of blindness. Here, we evaluate whether diabetes causes changes in the way neurons signal to blood vessels, and whether blocking some of the signals from neurons reduces blood vessel abormalities. Overall, this information is critical to our understanding of the early changes that occur during diabetes and whether novel treatments used early in diabetes can prevent long term changes and vision loss.
Dissecting Brain Network Ageing Using Whole Brain Imaging
Funder
National Health and Medical Research Council
Funding Amount
$692,964.00
Summary
In this proposal, we will make the first attempt to map the whole brain activity change during ageing using a series of state-of-the-art techniques. We will also identify genetic and pharmacological interventions that improve brain network function during ageing. Outcomes from this research will provide an unprecedented understanding of functional ageing within the brain and identify therapeutic interventions to prevent this process.
Organisation Of The Genome During The Development Of Antibody-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$886,155.00
Summary
Each cell of our body contains over two metres of DNA that must be correctly packaged in order for our cells to function. We are using cutting-edge molecular biology techniques to study how this DNA circuitry is established in the white blood cells of our immune system that produce antibodies. Our novel approaches will reveal unique strategies to modulate immune responses to our benefit.
A Novel Interaction Between The Immune And Vascular Systems In Early-onset Preeclampsia; An Opportunity For New Treatments?
Funder
National Health and Medical Research Council
Funding Amount
$921,623.00
Summary
Preeclampsia is a pregnancy complication that leads to poor birth outcomes and elevated lifelong cardiovascular disease risk in 4 million women each year. It has no cure and treatments are limited because the causal mechanisms are not understood. We have identified a specialised immune cell in the mother's blood that assists blood vessels to function properly in pregnancy. We will assess whether interventions to enhance these cells can improve poor blood vessel function and pregnancy outcomes.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Advancing The Spatial Analysis Of Cells In Tissues To Profile The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$187,918.00
Summary
Tumours are composed of a mix of different cells, including cancer cells, immune cells and other cells supporting tumour growth. These cells are not organised randomly, but rather are distributed in specific patterns. Here we will develop computational methods to detect these patterns and determine what statistical tests should be used to compare samples. This project will give us the tools to investigate how the location of cells in tissues relates to treatment response and survival.
Identifying Unintentional Effects Of Medication Using Statistical Genetics Analyses Of Large-scale Genetic And Genomic Data
Funder
National Health and Medical Research Council
Funding Amount
$251,441.00
Summary
An increasing number of studies have highlighted unknown adverse effects of medication, for example, use of statins to lower cholesterol with increased risk of type 2 diabetes. The gold standard approach to confirm these effects is randomised control trials, which may not always be feasible or ethical, and are very expensive. This project aims to apply innovative statistical genetics approaches to (genetic and genomic) 'big-data' to predict unknown effects of commonly prescribed medications.
Sudden cardiac death (SCD) is a devastating consequence of a number of heart diseases. Underlying causes include inherited heart muscle problems (cardiomyopathies), with no cause found in 40%. Our study will investigate the role of 'concealed cardiomyopathy' cases, i.e. those with a SCD event with no evidence of heart disease, but carry errors in heart genes. Our findings will translate rapidly into more targeted clinical and genetic evaluation of families with the ultimate goal to prevent SCD.
Biomechanics Meets Phenomics: Towards Understanding And Predicting Abdominal Aortic Aneurysm (AAA) Disease Progression
Funder
National Health and Medical Research Council
Funding Amount
$1,324,897.00
Summary
The criterion used to decide whether to operate on an abdominal aortic aneurysm (AAA), based on the maximum diameter, does not take into consideration the rupture risk for a given patient. By combining imaging, computational biomechanics and metabolic phenotyping, we will assess the structural integrity of an AAA and local structural changes of systemic response. These will allow improved differentiation of rupture risk, leading to better outcomes for patients and savings for the health system.