Chromosomes are tiny packages that contain the essential genetic material of life. Each chromosome needs to be replicated and segregated into newly divided cells for healthy human development. The work of the Chromosome Research Group aims to understand how errors of chromosome segregation lead to human diseases such as Down syndrome, cancer, infertility and premature ageing. Results from this research will assist families in understanding the disorder and may have the potential in treatment or prevention in the future.
Chromosome instability and disorders of sex development (Dr Paul Kalitsis)
Approximately 10 quadrillion cell divisions occur in the lifetime of a human. For each cell division, chromosomes must be copied and distributed faultlessly into the daughter cells for normal human development to occur. Failure of chromosomes to segregate accurately is commonly associated with health problems such as birth defects (eg. Down syndrome), cancer, premature aging and infertility, and is indeed the single biggest cause of miscarriage. With the use of state-of-the-art technologies, such as live-cell imaging, flow cytometry with chromosome-sorting capability, mass spectrometry/proteomics, RNAi and embryonic stem cells, this project aims to identify genetic and epigenetic factors that compromise the faithful transmission of chromosomes in humans and mice, with a focus on disorders of sexual development. The results gained form this study will significantly advance our understanding of the causes of chromosome-instability disorders and allow the future development of appropriate diagnostic and preventative measures.
The role of centromere defects in cancer formation and progression
The centromere is an essential chromosome structure required for the transmission of replicated DNA to daughter cells during cell division. It has been shown that chromosome instability (CIN) may be associated with cancer development, but there has been no systematic study of the role of the centromere in different cancer types. The hypothesis is that centromere abnormalities are common and a key factor in cancer development, and this study proposes to determine the extent, form and functional significance of centromeric defects within cancer. The study will yield valuable insight into the roles centromeres play in the onset and progression of cancer. This knowledge will complement existing large-scale cancer genome sequencing projects and translate into a better understanding of the causes and biomarkers of cancer.
The compaction and folding of DNA is one the most visually dynamic processes in biology. It is central to the faithful segregation of chromosomes into daughter cells. Correct organization of DNA within the nucleus is also essential for controlling gene transcription. Researchers in the group have identified a master regulator of chromosome compaction known as the condensin complex. This is a very new line of research and is providing important clues as to why mutations in the condensin complex are increasingly associated with cancers and developmental disorders.
- Active centromere and chromosome identification in fixed cell lines. 2016
- Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis. 2016
- Condensin I and II behaviour in interphase nuclei and cells undergoing premature chromosome condensation. 2016
- Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome. 2016
- PICH promotes mitotic chromosome segregation: Identification of a novel role in rDNA disjunction. 2016
- Proteomics Analysis with a Nano Random Forest Approach Reveals Novel Functional Interactions Regulated by SMC Complexes on Mitotic Chromosomes. 2016
- Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo. 2015
- Contribution of the two genes encoding histone variant h3.3 to viability and fertility in mice. 2015
- Disruption of a conserved CAP-D3 threonine alters condensin loading on mitotic chromosomes leading to chromosome hypercondensation. 2015
- Three-dimensional topology of the SMC2/SMC4 subcomplex from chicken condensin I revealed by cross-linking and molecular modelling. 2015
- Chromosome Y centromere array deletion leads to impaired centromere function. 2014
- Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes 2013
- PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells. 2013
- Contrasting roles of condensin I and condensin II in mitotic chromosome formation 2012
- Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase II alpha 2012
- Putative CENP-B paralogues are not present at mammalian centromeres. 2012
- The evolutionary life cycle of the resilient centromere 2012
- Prof David Amor, Victorian Clinical Genetics Service, Murdoch Childrens Research Institute
- Dr Mark Pertile, Cytogenetics Laboratory, Victorian Clinical Genetics Service, Murdoch Childrens Research Institute
- Prof William Earnshaw, Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, UK
- Dr Jeff Mann, Germ Cell Epigenetics, Murdoch Childrens Research Institute