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Unlocking patterns of nature

Adrian Wan

A zebra's stripes, a seashell's spirals, a butterfly's symmetrical wings - patterns in nature have fascinated people for millennia. And the question of how they are formed has baffled scientists for centuries.

But now a team of Hong Kong scientists has helped unlock the mystery. Working with other scientists, they spent three years on a fundamental question: how do living cells arrange themselves to form such beautiful and ordered patterns in multicellular organisms?

Using a new approach, they uncovered not the whole answer, but a basic principle that will allow them to control and form an organism's pattern by tweaking and changing bits of its genetic formula. These insights will be useful for further research in genetics and medicine.

'Questions like why human beings have five digits in each limb, whereas cattle and horses only have two and one, respectively, have always interested me,' said Dr Huang Jiandong, associate professor of biochemistry at The University of Hong Kong.

'We now understand the logic behind why and how living organisms form in certain ways, which brings us closer to being able to control how things will grow.'

Huang led about a dozen in a team of researchers from Baptist University, the University of California in San Diego, the University of Marburg in Germany, as well as HKU.

Dr Liu Chen-li, of HKU's biochemistry department, said: 'Questions like this have been studied for centuries, and our research couldn't have answered all the questions - we can never do that - but it is a first step in an entirely new direction.'

The findings explain some basic principles in biology, which are crucial for developing regenerative medicine, such as growing organs and tissues or using stem cells to repair damaged organs. However Huang said the findings were still far from applicable to medicine, as the study was only done on a very basic form of bacteria.

'If you look at the biological structures of human beings, there are a lot of repeated structures like the number of our fingers. How can we tune this to create different numbers for different organisms?' Huang said.

'[Our] study addresses a fundamental question in biology: 'how do living cells arrange themselves to form beautiful and ordered patterns in multicellular organisms?'

The researchers designed a synthetic genetic programme and applied it to E coli bacteria, successfully controlling how it grew. The scientists easily managed to alter the number of stripes formed by the bacteria. That may help scientists to understand how different numbered biological features are formed in different organisms, and may provide new thinking to control their formations.

The findings are published in the latest issue of Science, a leading international research journal. 'It is the first paper on synthetic biology in Hong Kong, or even in China,' said Liu. 'It is a breakthrough.'

The development from a single cell into a full-sized organism is a complex yet organised process. It involves cells differentiating into various different cell types, as well as the co-ordination of cells in space and over time to form orderly structures.

In recent years, a lot of effort has been put into cell differentiation with the advancement in stem cell reprogramming. Yet little is understood about the formation of orderly structures due to the underlying complexity in biological systems.

The research found that patterns such as the hundreds of vertebrae in a snake's spinal column are formed by specific genetic formulas. In nature, repetitive patterns and structures are precisely controlled. Yet it is difficult through genetic engineering to create repetitive structures and to control the number of repeats. Huang's research will help make such engineering easier.

The study combined systems biology, quantitative biology, synthetic biology and physics. 'It was very difficult at first to get people from different fields together because we all spoke different languages,' Huang said. 'Biologists speak one language and physicists speak another. So one of the difficulties was to iron out the basic differences before we could move on.'

He said it was worth the trouble because fundamental scientific problems like this typically did not involve only one field, making it necessary to bring together scientists with varied expertise.

Liu said: 'People are saying this will be a model for scientists around the world to follow.'

The team is looking at transferring the knowledge they learned with bacterial cells to mammalian cells.

Huang said scientists had said amazing things about the findings - in particular the team's new way of thinking to understand the quantitative control of a cell's structure formation in the development process, which is expected to be widely followed by other scientists in the field.

He encouraged the government to support fundamental research such as this because 'knowledge needs to be accumulated' bit by bit.

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