Kiwi scientists shed new light on disease

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Kiwi scientists have attracted global attention for shedding new light on how our cells switch their genes on and off - an important step to understanding disease.

The new findings by an interdisciplinary scientific team from Auckland-based Gravida, the National Centre for Growth and Development, were classed as a breakthrough when published recently in the major journal Nucleic Acids Research.

The team of microbiologists, physicists and geneticists, led by Dr Justin O'Sullivan of the University of Auckland, uncovered new explanations for how the "on/off" switch in our genes works.

Dr O'Sullivan described their findings as an "essential insight" into the nature of disease.

"If you have the wrong combinations of chromosomes associated together in space, you could be turning the wrong functions on and off in the genes."

By studying the shape and structure of the DNA inside the cell, the team discovered for the first time a microscopic, effortlessly efficient organisational structure that is linked to when genes turn on and off.

This switching of genes distinguishes each cell, of which there are about 200 different types in the body.

While all share the same DNA information, each have completely different functions.
A skin cell and a hair cell are genetically identical, for example, but different, specific genes in them are turned on and off.

"How is it that cells are different, even though they have the same DNA?" Dr O'Sullivan said.

"With this paper, and an earlier one, we think we have discovered part of the mechanism."
There had been strong interest from around the world since the Gravida team's research was published late month, he said.

While it had long believed the DNA in a cell was arranged randomly and chaotically, the team has suggested the DNA's make-up in a nucleus is actually ordered.

Dr O'Sullivan described the DNA as being "folded" within the nucleus, so that certain parts of DNA and certain genes or chromosomes are juxtaposed together.

"This means certain genes come directly into contact."

The genes are mapped together deliberately in the nucleus, creating an efficient process.

"It means that genes and chromosomes that need to work together to make cells different from one another don't have to wander around the nucleus trying to meet up."

Chromosomes and genes met, he said, because they were folded together quite precisely.

"For the first time, we've shown you can't separate the structure of a cell from its function.

"If a cell has a different structure, if the DNA is folded a certain way in one cell and not in another cell, the cell itself has a different function.

"The juxtaposition of chromosomes and genes is linked to genes turning on and off."

Furthermore, the structure was self-organising, with the cell not functioning in a way that required membranes.

The team related this new finding to another recently published and completely novel research discovery, finding that the mitochondria within cells also directly connects with genes that are turned on.

Previously, most scientists believed that the mitochondria was simply the cell's powerhouse, and had nothing to do with nuclear genes.

Gravida director Professor Phil Baker described the research as "a leading edge discovery".

"There are only a couple of other labs around the world doing this sort of work, and Gravida's team is the first to discover this."