Straits Times : Tiny fish may hold key to cancer cure

JUL 02, 2002

Tiny fish may hold key to cancer cure

The zebrafish, whose genes are similar to human genes, may show scientists how liver cancer occurs

AN AMBITIOUS new project has brought to- gether one of the biggest scientific teams here to study the zebrafish, in the hope that the tiny, transparent creature will help them understand how cancer develops.

The effort, which has garnered $5.5 million in government grants, will see about 50 researchers, including principal scientists, post-doctoral research fellows, PhD and master's students, working together for the next five years.

Assistant Professor Low Boon Chuan, who is from the National University of Singapore's (NUS) department of biological sciences and a principal investigator in the group, told The Straits Times that, like humans, zebrafish can be prone to cancer.

'We will be studying the culprits that cause liver cancer - what genes are being either activated and turned off when the disease occurs, as well as the role of carcinogens.

'Then, we may be able to design drugs to block the genes or cancer-causing proteins from working,' he said.

The team decided to focus on liver cancer because it is a very common form of cancer in the Asia-Pacific region but there are not enough studies done on it.

In Singapore, liver cancer is the fourth most common cancer among men, with about 400 new cases a year. It is uncommon in women.

Prof Low said the zebrafish had been chosen because it has genes which are similar to human genes.

'Because its body is transparent, we can look at how the embryos are developing and actually see which genes have been activated and where this is taking place in the fish,' he added.

A flagship project of the newly-set-up Genome Institute of Singapore (GIS), the zebrafish group is headed by big names such as the institute's executive director - cancer expert Edison Liu.

Senior researchers leading the team will also come from NUS and the Institute of Molecular Agrobiology.

One of them, Dr S. Mathavan, a research scientist at GIS, said that at his institute, researchers had top- of-the-range equipment for micro-array analysis - a technology used to look at large numbers of genes simultaneously.

'We will be studying about 16,000 zebrafish genes at any particular time, after exposing them to cancer-causing toxins, drugs or hormones.

'So, we will be able to see how different genes react in liver cancer,' he said.

Apart from research, the project aims to train more than 20 PhD and master's students, as well as a dozen post-doctoral students.

Associate Professor Gong Zhiyuan, from the NUS department of biological sciences, is an expert who has been working with zebrafish for seven years.

He has produced transgenic red, green, yellow and orange fish with fluorescent genes from jellyfish and sea anemones, which can be used as warning markers to glow in the presence of pollutants or cancer-causing toxins, for example.

'The beauty of the zebrafish lies in it being transparent... we can see exactly what happens when we manipulate its genes.

'We're at the forefront of such research, which should answer a lot of questions about why liver cancer occurs and how to prevent or treat it,' he said.

ZEBRAFISH: Research boon

IT SHARES many of the same genes as humans, so work on the zebrafish genome can shed light on how the same genes work in humans.
The 2.5-cm fish can be kept and bred in the lab. The facilities at the National University of Singapore house some 2,000 fish. Each fish has a lifespan of about two years. After maturity at three months, the female fish lays more than 200 eggs a week.
As it is transparent, researchers can study the embryo development with ease, unlike with other popular experimental animals such as mice and rats.
In recent years, scientists have started using the zebrafish to study human diseases, including mutant genes that cause blood and kidney disorders.
Singapore already has more than 10 years of expertise in working with the zebrafish. Researchers have been able to produce transgenic fish - those with genes from other animals - which could be used to detect cancer-causing agents or environmental pollution by emitting a glow.
Despite more than 300 million years separating the last common ancestor of the human and fish, many substances which cause cancer in humans also cause cancer in zebrafish, and it is likely that cancer develops the same way in both species. The Singapore group is the first in the world to use the zebrafish to study liver cancer.