Precision Molecular Diagnostics Of Single Cells By Imaging Flow Cytometry
Funder
National Health and Medical Research Council
Funding Amount
$875,110.00
Summary
We have invented a highly sensitive, new method to count and evaluate chromosomes inside cancer cells. With this world-first method we can detect abnormal chromosomes when fewer than 1 cell in 1,000 is affected. We will refine the method for assessment of blood cancers and chromosome disorders such as trisomy 21 (Down Syndrome), and commence pre-clinical testing. This is a critical step towards translating this methodology into a validated test to significantly benefit human health.
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.
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