Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
Role Of Condensin In Chromosome Organisation And Regulation
Funder
National Health and Medical Research Council
Funding Amount
$589,425.00
Summary
When a cell divides, its hereditary material (DNA) must be copied and equally segregated into each daughter cell. Our DNA is organised into a number of long units known as chromosomes. In order for our genetic material to be faithfully segregated into two daughter cells, the chromosomes must compact nearly 10,000 fold. A key component is condensin and we aim to find out how condensin directs the organisation and compaction of the mammalian chromosome.
Regulation And Role Of Transcription At The Centromere.
Funder
National Health and Medical Research Council
Funding Amount
$737,801.00
Summary
Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that ....Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that bind to it. In our preliminary work, we have demonstrated that a novel non-protein component in the form of RNA (which are expressed products of genes) is essential for the binding of key proteins to the centromere. The presence and importance of such an RNA component has not been previously suspected and represents an exciting new mechanism that help to determine the functional and structural integrity of the centromere. In this project, we propose to study the details of this RNA and to define how this RNA-related mechanism operates to ensure the proper assembly and function of the centromere during cell division.Read moreRead less
Studies in humans and model organisms have shown that defects in centromere function result in chromosome abnormalities and copy-number changes that constitute a major cause of aneuploid-related syndromic disorders, intellectual disability, infertility, pregnancy loss, and cancer. Understanding the biological properties and functions of the centromere is therefore a high priority for health research.
Pathogenesis Of Vascular Shock And Platelet Dysfunction In Sepsis: The Role Of Calcium Desensitization, Statins And Cortisol.
Funder
National Health and Medical Research Council
Funding Amount
$89,778.00
Summary
Severe infections are characterised by a profound drop in blood pressure, which starve vital organs of oxygen and nutrients, this �septic shock� can lead to organ failure and death. We aim to identify dysfunction of the molecular signals in blood vessels, which leads to the failure of these vessels to maintain adequate blood pressure. Understanding the mechanisms regulating blood pressure during septic shock will enable us to develop therapies to support the circulation and reduce the significan ....Severe infections are characterised by a profound drop in blood pressure, which starve vital organs of oxygen and nutrients, this �septic shock� can lead to organ failure and death. We aim to identify dysfunction of the molecular signals in blood vessels, which leads to the failure of these vessels to maintain adequate blood pressure. Understanding the mechanisms regulating blood pressure during septic shock will enable us to develop therapies to support the circulation and reduce the significant death toll from life threatening sepsis.Read moreRead less