6. «Super-tough» bugs to improve cancer research

Almost-indestructible microbes that survive and thrive in hot sulphuric acid pools as well as freezing polar terrain are being studied by space sci­entists because the organisms rep­resent the type of life most likely to be found elsewhere in the solar sys­tem.

The "super-tough" bug research is expected to improve our understand­ing of the origin of life and, eventu­ally, reveal whether life is confined to our planet or is distributed more widely.

And in similar work elsewhere, sci­entists at a top university in United Kingdom are making good progress with much more down-to-earth stud­ies after focusing on this incredibly strong family of microbes - called Archaea.

These almost immortal minute creatures have many similarities to humans in the way they replicate and repair their DNA, shedding new light on the workings of the human body. Because of their extreme lifestyle, Archaea proteins are very robust and often easier to study than the equiva­lent human proteins.

A research team at the University of St. Andrews, Scotland, recently made a startling advance relevant to human diseases and they are continuing to es­tablish if it could prove to be a useful weapon in the fight against cancer.

Led by Professor Malcolm White, the team at the Centre for Biomolecular Sciences at St Andrews made the discovery while investigat­ing proteins - called helicases - that separate strands of the genetic ma­terial DNA.

Helicases are vital for the replica­tion and repair of DNA (deoxyribo­nucleic acid); defects in these pro­teins can lead to increased rates of cancer In humans.

The team found that a family of helicases important for the avoidance of breast and skin cancer incorporates a cluster of iron and sulphur atoms. This "Iron-sulphur cluster" is essential for the activity of the helicases, and mutations in humans that prevent the cluster forming _tare known to lead to severe cases of early onset cancer.

Professor White paid tribute to the Association for International Cancer Research for funding the study and added: "Iron is very important in the body but no-one had suspected this link with DNA repair. The discovery was only possible because we inves­tigated a simple model organism - it would have been very difficult to study the human proteins. This emphasises the need for basic research as part of our efereto understand and com­bat cancer."

He added: "Credit must also go to the student who made the discovery, Ms. Jana Rudolf. She has now been funded by the charity Cancer Research UK to continue her studies."

It was in 2002 that Professor White discovered that archaea have unex­pected similarities to humans. He ex­plained: "Because the archaea are so simple they are much easier to study, SO that is really our reason for work­ing with them. They only have 3,000 genes whereas we have well over 30,000 genes.

"The other main point is that this work changes the way we think about these so-called 'primitive' forms of life - they may be more sophisticated than we had thought and, therefore, more similar to man."

Many archaeans are extremophiles. Some live at very high temperatures, often above 100 degrees Celsius, and are found in geysers and around "black smokers" - volcanic chimneys rising from the seabed. Others are found in very cold habitats or in highly saline, acidic or alkaline water.

Other archaeans are mesophiles and have been found in environments such as marshland, sewage, sea water and soil. Many methanogenic archaea are found in the digestive tracts of animals such as ruminants, termites and humans. Archaea are usually harmless to other organisms and none is known to cause disease.

Professor White said that the work had only been possible because re­searchers could pool theit expertise in research centres such as the Centre for Biomolecular Sciences, where scien­tists from different disciplines are brought together in world-class labo­ratories with state-of-the-art equipment.

At the biomolecular sciences cen­tre, Professor White is renowned as an expert on archaea proteins that are ideally suited for structural stud­ies. Describing his work in more de­tail, he said: "ONA is subjected to continual assault by a variety of chemical, enzymatic and environmen­tal factors, and must be repaired ac­curately and swiftly to maintain the in­tegrity of the genome. Multiple re­pair pathways have evolved to fulfil this role, including nucleotide exci­sion repair and homologous recom­bination.

"We are studying these pathways in the archaea - a group of prokaryotes that represent a third domain of life, distinct from both eukaryotes and bacteria. Archaeal information processing pathways (for example transcription, translation, DNA repli­cation) are good models for the equivalent, more complex pathways in eukaryotes.

"We ' are identifying and characterising archaeal proteins im­portant for DNA repair and recombi­nation, using a multi-disciplinary ap­proach that includes biochemical, bio­physical, molecular biological and genetic techniques, with the aim of defining the relevant components and mechanisms- This work will yield insights to the equivalent processes in eukaryotes, including humans, that are essential for the avoidance of cell death and carcinogenesis," he added.

The School of Chemistry provides an outstanding environment for re­search and study. Chemical research has a long and distinguished history at St. Andrews. In recent years, sev­eral named prizes of the Royal Soci­ety of Chemistry have been awarded to current members of the school.

By Richard Maino