The Role Of Centromere Defects In Cancer Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
When cells divide, their DNA must be copied and distributed faultlessly into the new cells. Defects in the factors that control this process will result in serious health problems including cancer. The objective of this project is to identify what these factors are and study how they contribute to cancer. Results gained from this project are expected to significantly increase our understanding of how cancer cells control the replication of their DNA and therefore their own fate.
Histone H3.3 Dynamics At The Telomere In Pluripotent Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,977.00
Summary
The telomere is required for the protection of the chromosome ends. Telomere loses its repeat during each cell division, so telomere shorthening is one of the mechanisms underlying organismal aging as critically short telomeres induce chromosome instability and cell death. Defective telomeres can also result in genetic diseases and development of cancers. Here, we propose to study the mechanism that operates to ensure continual telomere renewal without senescence in embryonic stem cells.
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
Mechanisms By Which Chromatin Modulates Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
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 both capable of blocking and activating gene expression. Therefore one important ....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 both capable of blocking and activating gene expression. Therefore one important function of chromatin is to tightly regulate 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 can result from the production of incorrect proteins. To control correct gene expression, highly specific mechanisms must operate in the cell to remove, or modify, 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 specialized forms of these histones (variants). We believe that these histone variants can specifically generate chromosomal domains which could in some cases expose or in other cases hide certain genes and thereby turn them on or off. Employing a new approach, we will study one of these histone variants to discover the role it plays in determining the type of chromosomal domain made and the role of this domain has in turning genes on or off at precise times in early development during the formation of different specialized cell types. This new information may define targets for the prevention of incorrect gene expression during cancer progression or abnormal development.Read moreRead less
A Universal Clinical Test For Gene Fusions In Blood Cancer
Funder
National Health and Medical Research Council
Funding Amount
$628,001.00
Summary
Mis-repair of broken chromosomes results in gene fusion and is a common feature of blood cancers. Current tests are only capable of detecting well-known gene fusions and are incapable of identifying new fusion events or fusion variations. We have developed a scientific technique, termed CaptureSeq, that can address these issues. We propose to use this technique as the foundation for a single clinical test for blood cancers, capable of detecting all possible fusion variations – known and unknown.
Genomic Signposts, High-resolution Sequencing And Novel Genes In Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$333,694.00
Summary
Blindness is a very distressing sensory loss. Hereditary eye disorders account for the vision impairment in at least one-third of people who are registered as blind. These disorders cause blindness from a young age and work productivity is significantly impaired. This project will identify novel genetic factors in blinding eye disorders. Identifying these genetic factors will lead to better early detection methods for people and improved treatments to prevent the blindness.
Diagnosing Chromosomal Translocations In Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$410,997.00
Summary
Mis-repair of broken chromosomes can fuse together genes that then cause cancer. Current clinical tests are only capable of detecting single well-known gene fusions and are incapable of identifying new fusion events or fusion variations. We have developed a diagnostic technology, termed CaptureSeq, that is capable of finding all fusion genes in a patient sample. In this grant, we will demonstrate the use and advantages of CaptureSeq for diagnosing fusion genes in cancer patients.
Using Mouse Models To Decipher The Function Of Caspase-2 In Limiting Aneuploidy Tolerance And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$871,162.00
Summary
Aneuploidy or abnormal chromosome number is a feature of cancer cells. The extent of aneuploidy is often predictive of prognosis and the effectiveness of cancer treatment. We discovered that a tumour suppressing protein, caspase-2, is important for deleting aneuploid cells that may otherwise become cancerous. In this project we will use cancer models to decipher how caspase-2 safeguards against aneuploidy and cancer to better understand how cancer cells can survive and be targeted for treatment.