Airway Epithelial IAPs And Their Interaction With Zn Ions
Funder
National Health and Medical Research Council
Funding Amount
$260,779.00
Summary
The air we breathe contains a variety of harmful substances. Damage to the lining involves death of the ciliated cells that line the airways. We have shown that zinc protects these cells from premature death. This application focuses on a family of proteins called IAPs which bind zinc and regulate cell death in other tissues. This project focusses on how the IAPs and Zn may act together to mainitain healthy airways and how abnormalities of these may occur in people with asthma.
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Preclinical Evaluation Of The Novel Therapeutic Compound APP96-110 In An Ovine Model Of Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$874,734.00
Summary
Traumatic brain injury (TBI) is a significant cause of death and disability, and yet there are currently no effective treatments to improve outcome following such an insult. Our laboratory has developed a novel therapeutic compound, by identifying an endogenous neuroprotective molecule, in the amyloid precursor protein and then identifying the active site and modifying it to improve its efficacy. We will be testing this compound in our sheep model of TBI.
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Normal heart development before birth. This project aims to understand how the fetal heart can develop normally with much less oxygen than an adult heart uses. Regulation of fetal heart proliferation is not well understood but changes in oxygen levels and non-coding RNAs are implicated. Using advanced imaging techniques to measure blood flow in blood vessels to the fetal heart and molecular probes to assess cell function and microarrays to measure non-coding RNA, the project expects to generate ....Normal heart development before birth. This project aims to understand how the fetal heart can develop normally with much less oxygen than an adult heart uses. Regulation of fetal heart proliferation is not well understood but changes in oxygen levels and non-coding RNAs are implicated. Using advanced imaging techniques to measure blood flow in blood vessels to the fetal heart and molecular probes to assess cell function and microarrays to measure non-coding RNA, the project expects to generate new knowledge about mechanisms of fetal heart cell proliferation. Ultimately, this new knowledge could lead to non-invasive approaches to detect and treat abnormal fetal heart growth in animals and humans.Read moreRead less
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blo ....Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blood flow and the exchange of expertise between leading researchers in Australia and Canada. In the long-term, this will enhance Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.Read moreRead less
Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow ....Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow and brain metabolism with exchange of expertise between leading researchers in Australia and Canada and their trainees. In the long-term, this should provide significant benefits in enhancing Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how t ....Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how the atypical cadherin FAT4 relays mechanical signals including flow and tension to the lymphatic endothelial cell skeleton, thereby enabling changes in cell shape important for building lymphatic vessels. This project will increase our understanding of how cells sense touch and may be applied for tissue engineering purposes.
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