Genomic research to investigate rare children's di
victoria-university-of-wellington
Mon Jul 30 2007 12:00:00 GMT+1200 (New Zealand Standard Time)
Genomic research to investigate rare children's di
Monday, 30 July 2007, 1:16 pm
Press Release: Victoria University of Wellington
MEDIA RELEASE
30 July 2007
Genomic research to investigate rare children's disease
The therapeutic effects of existing pharmaceutical drugs on a rare disease affecting one in 2000 children is under investigation by Victoria medical researchers using a new, specialised microscope.
Led by Professor Paul Atkinson and David Bellows in the University's School of Biological Sciences, the research aims to identify a cure for a congenital glycosylation disorder that results in a range of paediatric diseases.
Professor Atkinson says the disorder occurs when an enzyme needed to made complex carbohydrates is missing – a cellular malfunction attributed to a specific gene mutation. The process making these carbohydrates is highly conserved in evolution allowing use of simple microbes to facilitate study of the disease.
"By modelling, or emulating, the disease in yeast, we will find where the enzyme acts in a normal yeast cell and where it is blocked in mutated cells. We can then screen for drugs that will correct the defect."
The study has been made possible with the purchase of an Opera EvoTech automated confocal microscope – worth approximately NZ$1 million and the only one of its type in New Zealand. Professor Atkinson says the powerful machine allows researchers to shift genomics, the study of the relationships between gene structure and biological function, up a major gear to the next level of phenotype screening where they can microscopically see the reaction of cell to a mutation or a drug.
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"This is a way of accessing a whole new level of information to help determine the genetic networks by which an enzyme is produced, and these are vast and complex networks that require intensive high throughput screening."
The microscope's five computers can take more than 100,000 2MB digital images a day, and use pattern recognition to interpret and sort microscopic shapes as part of the screening process. A unique water-immersion lens increases its aperture, resulting in a 50-fold increase in resolution.
For this particular task the microscope works in tandem with robotics equipment in the Chemical Genetics Laboratory – a highly specialised and unique laboratory that opened one year ago with funding from the Tertiary Education Commission. Chemical geneticists delineate genetic networks by conducting high throughput screening of living cells, and their research has a direct spin-off for novel drug discovery, disease diagnostics or prediction of side-effects.
One robot in the sequence of machines leading up to the Opera EvoTech will fill plates with yeast cells in solution, and another will add pharmaceutical chemicals to each with a precision that is unachievable by hand. The plates are then inserted into the microscope for screening.
Professor Atkinson says finding the right drug that acts as a "chemical chaperone" is not simply a matter of testing several hundred chemicals.
"Drug discovery has slowed down significantly in the past decade because scientists have discovered nearly all of the drugs that have a single gene targeting ability, in the case of simple diseases. Now it's all about discovering the combinations of genes to target with combinations of drugs, for complex diseases.
"We need to know the networks of genetic interactions to do so, because there is usually more than one biochemical pathway leading to the production of an enzyme a redundancy cells have evolved to protect themselves."
He says the major genomics research of the late '90s identified yeast, with similar enzyme pathways to humans, as an ideal organism on which to model human cellular processes.
About congenital disorder of glycosylation (CDG).
- it is estimated that at least a dozen new cases occur in New Zealand annually, but they are often assigned to another disease class.
- The disorder can result in a spectrum of severe diseases such as psychomotor retardation and seizures, and is estimated to incur costs of more than $NZ one million over a patient’s lifetime.
- In severe cases children may die before reaching adulthood.
ENDS
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