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.
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.
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
Centrosome Overduplication Contributes To Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$495,010.00
Summary
Cancer can be simplistically thought of as a disease of cell growth and division. In order to improve current treatment regimes and identify new ones, the underlying mechanisms controlling cell proliferation need to be fully understood. By defining these regulatory mechanisms, targets for current chemotherapeutic agents can be further characterised and new ones identified. This will lead to the targeted developments of new classes of drugs which can be used in the fight against cancer.