Understanding The Cardio-protective Actions Of The AT2R In Females: Shifting Gears Between AT1 And AT2 Receptor Balance Of Function With Relaxin.
Funder
National Health and Medical Research Council
Funding Amount
$1,049,288.00
Summary
Women are protected from cardiovascular disease as compared to age-matched men, an effect lost with age. Understanding protective factors that act in females could be used to treat hypertension, heart failure and stroke in males at all ages, and maintain protection in elderly women. Our studies aim to determine if relaxin, an ovarian hormone, can promote cardiovascular health in women.
The Role Of Heterochromatin In Regulating Cellular Proliferation And Development
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the ....Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein (histones) to form a structure known as chromatin. It has become clear that the chromatin structure encompassing a gene is the critical factor that determines whether a gene is expressed or silenced. We propose that developmental and cell-type specific mechanisms operate in a cell to assemble genes into highly specialised chromatin structures that permit (euchromatin) or restrict (heterochromatin) gene expression. In other words, the genome of each different cell type is organised into a unique and dynamic chromatin pattern and this pattern determines the gene expression profile. This investigation will show that the critical cellular mechanism that determines the chromatin pattern for a particular cell type is the regulation of the quantity and quality of heterochromatin. Specifically, we will demonstrate that this is achieved, in a developmental and tissue specific manner, by changing the make-up of chromosomal domains through the replacement of histone proteins with specialised forms of histones called variants . In addition, we will expose a new mechanism of how heterochromatin formation controls the rate of cellular proliferation. This information will provide new insights into how gene expression profiles are established at precise times in early development, and offer a new strategy to inhibit the proliferation of cancer cells.Read moreRead less
The Function Of An Essential Histone Variant During Early Development.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is capable of blocking gene expression therefore one important function of chromati ....Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is capable of blocking gene expression therefore one important function of chromatin is to prevent unwanted gene expression which is essential to allow an organism to develop properly. When gene expression is not accurately controlled by chromatin developmental defects or cancer could result from the production of incorrect proteins. To control correct gene expression, highly specific mechanisms must operate in the cell to remove, or disrupt, nucleosomes at certain genes at a precise time during development. One mechanism that we believe to be important is changing the make-up of a nucleosome. This can be achieved in the cell by the replacement of histones with different specialised forms of these histones (variants). It is thought that these histone variants could specifically expose certain genes and thereby turn them on. Once the correct protein is made in sufficient amounts the histone variants could be rapidly exchanged for the normal histones to shut off the gene. Employing a new approach, we will study one of these histone variants to discover the role it plays in turning genes on at precise times in early development during the formation of different specialised cell types. This new information may define targets for the prevention of incorrect gene expression during cancer progression or abnormal development.Read moreRead less
Application Of Adult Stem Cells To Bioengineered Corneal Epithelium And Endothelium Autografts
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Damage to the cornea causes vision loss. Transplants can restore sight but carry risk of rejection and therefore require anti-rejection therapy, which has side effects. Bioengineered corneal components could replace transplants. Our goals are: 1) Growth of corneal endothelium and epithelium from adult stem cells to reduce the amount of tissue so the patient's own cells could be used. 2) Develop scaffolds that are suitable for implantation or other methods to deliver cells.
Improving The Functional Outcomes Of Lower Limb Orthopaedic Surgery
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
While orthopaedic surgery usually achieves pain relief and improves function somewhat, it can often leave a patient unable to perform certain activities. And these abnormal movement patterns are likely to cause further problems. This project will objectively measure post-surgical function, in order to improve the surgery and rehabilitation of some of the most complex orthopaedic conditions. The goal is that patients receive the maximum benefit from surgery.
Periodontal Mesenchymal Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$358,000.00
Summary
Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characteriz ....Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Femoroacetabular impingement (FAI) is a common cause of hip pain characterised by extra bone formation at the hip, called a cam-deformity. FAI is thought to create hip joint damage and osteoarthritis. Our 5 year longitudinal study of people with FAI in two (Melbourne and Brisbane) sites will investigate whether factors (such as cam-deformity size, hip contact force, muscle strength and joint range) can predict hip joint damage (measured with magnetic resonance imaging) over two years.