Spatial arrangement and three-dimensional structure of human centromeres

Funded Activity Summary

Centromeres occur at the main constriction of chromosomes. They allow duplicated chromosomes to divide, control cell division and are involved in the control of gene expression. Faulty centromeres are found in many types of cancer and in other genetic diseases. They are also implicated in extra-chromosome disorders such as Down syndrome. Centromeres have a different structure to the rest of the chromosome and it is this structure we wish to study. We want to see how centromere DNA folds up tightly at the centromere. We also want to find out why centromeres locate in certain regions of the nucleus, because this may influence how the centromere works and how they regulate genes. Human centromeres come in many sizes and forms; by looking at a wide range of human centromeres, common structural and spatial properties will emerge. We have discovered very small centromeres - neocentromeres - which are much easier to study than other centromeres. We have used these centromeres to construct human minichromosomes, which we believe represent the main, all-human way forward to treat people with gene therapy. One way to help us achieve our aims is to stretch out centromeres in a controlled way to make it easier to visualise their structure. Our tools will be antibodies, fluorescently-labelled proteins and high resolution microscopes. These include an electron microscope, and microscopes that can produce optical sections and in turn a 3D image. One of these is the confocal laser scanning microscope; the other involves removal of out-of-focus light from images using deconvolution software to achieve the same goal. We will detect different centromere proteins with different fluorochromes for fluorescence microscopes and different sizes of gold particles for the electron microscope. Using these microscopes we have already been able to find out where one of our neocentromeres is located within the nucleus. We have also started to look at centromeres with the electron microscope.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $283,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cell Development, Proliferation and Death

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

cancer predisposition | centromere structure and function | chromatin structure | chromosomal abnormality | confocal microscopy | electron microscopy | genetic disease | infertility | mitosis

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