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“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.
Bug watcher: Jana Rudolf (pictured) is part of a research team studying
“super-tough” organisms at St. Andrews University, Scotland. She recently made a
startling advance relevant to human diseases, especially cancer. Cancer Research UK is
funding her to continue her studies.
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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 incorporate 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 are 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 efforts to
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: “DNA 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
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