Research publications
All of the group's publications can be found in OURArchive, the University of Otago's institutional repository.
Chromosome Structure and Development publications
Research projects
Investigating how cohesin organises DNA in neurons and the impact of cohesin deficiency on brain function
The way DNA is packaged in brain cells is crucial for normal brain function. When this process goes wrong, it can lead to complications resulting in epilepsy and intellectual disability.
This research will look at how disruptions to the DNA ‘packaging’ alters individual brain cells and their wider connections. It ultimately aims to uncover new insights into neurodevelopmental disorders and develop more effective treatments.
This work is funded by the Royal Society of NZ Marsden Fund
Investigating a new drug target in acute myeloid leukaemia
It is rare to identify completely new genetic pathways that lead to cancer. However, the incentive to do so remains strong, to identify novel opportunities for therapeutics. Recent whole genome sequencing approaches have pinpointed mutations in genes that were previously not associated with cancer. For Acute Myeloid Leukaemia (AML) this approach revealed that 9-13% have mutations in genes encoding the chromosome cohesion complex, cohesin.
Cohesin mutations represent a new genetic pathway for AML, but how AML arises from these mutations is unknown. We are using multiple molecular approaches in leukaemia cells and a zebrafish in vivo model to determine how cohesin mutations lead to AML. We are also screening for drugs that selectively target cohesin-mutant leukaemias, and characterising their activity in human cells and zebrafish.
The work is funded by a project grant from the Health Research Council of NZ
Investigating a developmental role for cohesin
A recently fertilised embryo contains rapidly dividing cells that have the potential to develop into any part of the body. One of life's biggest mysteries is how cells in the early embryo decide what to be. Cohesin proteins are essential for both chromosome duplication and for controlling expression of specific developmental genes. Cohesin also regulates genes that promote stem cell identity. Therefore, we hypothesise that cohesin forms a vital link between cell division and differentiation.
Mutations in cohesin proteins are associated with developmental defects and human syndromes, e.g. Cornelia de Lange syndrome. In this research project, we are using zebrafish to investigate cohesin function during development, in particular, during stem cell commitment and zygotic genome activation.
As part of this project, we are using high throughput sequencing to determine how cohesin activates genes for the first time in the developing embryo. To find out if cohesin activates developmental genes in uncommitted cells, we are measuring expression of cohesin-bound genes during cell differentiation, and are determining if cohesin depletion changes their expression. The gene occupancy of cohesin will be aligned with other chromatin proteins signifying gene activation, or stem cell identity.
This work is supported by the Royal Society of NZ Marsden Fund