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Embargo: 10.30 am Wednesday 8 June 2005
Embargo and launch: 10.30 am
Wednesday 8 June:
30 Flemington Road, Parkville, beta sp and stills available
Many parasites are hard to fight
because their cells are so similar to ours that the drugs we use kill our cells
too.
Now, Bio21 Institute researchers at
the University of Melbourne have discovered a potential Achilles’ heel which
could allow us to take on the parasites that cause millions of human deaths
worldwide from leishmaniasis and tuberculosis, without the cost to our own
cells.
While leishmaniasis is largely unknown
in the West, it infects at least 12 million people worldwide and is re-emerging
in the West.
Americans troops returning from Iraq
have been told not to give blood for a year to prevent the possible spread of
the parasite into the US blood supply. Last year, the parasite was found in
kangaroos in northern Australia.
Spread by mosquito-like sandflies, the
leishmania parasite infects certain white blood cells known as macrophages. Its
biochemistry is so close to ours that the drugs used to fight it also damage our
own cells.
No more. A research team, led by Bio21
biochemist Assoc Prof Malcolm McConville, has discovered the parasite doesn’t use glucose
for energy storage, as we do. It uses a different sugar, mannose, instead.
The discovery was announced today at
the opening of the University of Melbourne’s $100 million Bio21 Institute by
Victorian Premier Steve Bracks.
“This is an exciting discovery that
opens the way to new drugs to fight parasitic diseases,” says Prof Dick
Wettenhall, director of the Bio21 Institute. “Now the biochemists and chemists
at the Bio21 Institute are working to identify drug targets. This is just the
kind of collaborative work using the latest equipment that the Bio21 Institute
was set up to do.”
“We expect the combination of
research, business, sophisticated laboratories and equipment at the Bio21
Institute, to transform the way the University turns inventions into real world
solutions,” says Prof Wettenhall.
The Bio21 Institute will grow in the
next 2 years to host up to 450 researchers (including more than 150 students)
and 15 companies.
“Our discovery not only offers hope
for leishmaniasis,” says Assoc Prof Malcolm McConville. “It may help us develop drugs for
many other microbial pathogens which use mannose – including those involved in
malaria and tuberculosis.”
A major problem in coping with
tuberculosis is the cell wall itself. “It stands alone from other bacteria,”
says Assoc Prof McConville, “a waxy, impervious barrier resistant to almost all commonly
used antibiotics.
“We’ve found that without mannose the
bacterium cannot form new walls and divide, and it eventually dies,” he says.
His team has already started work on development of potential drugs that will
target this weakness.
Background
More about Leishmania and the Bio21 discovery
A discovery by
researchers at the Bio21 Institute has opened up a significant new front in the
fight against leishmaniasis—a common and potentially lethal disease of the
developing world which has become a particular problem for the occupying forces
in Iraq.Americans troops returning from Iraq
have been told not to give blood for a year to prevent the possible spread of
the parasite into the US blood supply. And in 2004 the parasite was found in
kangaroos in northern Australia.
Spread by mosquito-like sandflies,
the protozoan parasite Leishmania buries itself inside the specialised
immune system cells, known as macrophages. The drugs used to eliminate the
parasite at present are highly toxic to its human host cells, causing serious
side effects.
Now, a group headed by biochemist
Assoc Prof Malcolm McConville has found that the Leishmania parasite uses
mannose, instead of glucose, as its key energy source. In fact, just as higher
plants and animals store glucose as starch or glycogen, Leishmania stores
mannose in the form another carbohydrate compound, mannan.
And there is good evidence, says
Assoc Prof McConville, that mannan is essential to the survival of the parasite in the
human body. So, any disruption of the production or breakdown of mannan could
kill Leishmania, leaving its human host cells untouched. “This
offers us the opportunity to develop a new class of highly specific drugs that
target only the parasite.”
Leishmaniasis is widespread
throughout the tropics and subtropics. In fact, Australia is the only
substantial tropical area where it does not occur. There are two main forms of
disease—cutaneous, which leads to sores on the skin, and visceral, a more
dangerous condition where the spleen and liver become enlarged. The US Centers
for Disease Control estimates more than 12 million people have leishmaniasis and
about half a million die of the visceral form each year.
In order to exploit the mannose
Achilles heel, Assoc Prof McConville has joined forces with chemist Dr Spencer Williams,
who is an expert at making carbohydrate compounds. The two groups are working at
pulling apart the series of reactions by which Leishmania builds and
utilises mannan. They then want to design and make compounds which can inhibit
this process. These will hopefully be the compounds which will lead to new drugs
to control the parasite, and treat the disease.
Such collaborative work using the
latest equipment is just the sort of job the Bio21 Molecular Science and
Biotechnology Institute was set up to do. Already the researchers have been able
to determine several of the compounds, enzymes and intermediates involved in
making mannan, which is a series of chains or polymers of mannose molecules.
They were in for a surprise right
from the outset. They found that the starter compound for the mannose chains
was, says Dr Williams, “a fundamentally new structure of carbohydrate—a cyclic
phosphate. It’s something I’ve never seen before, a truly exciting result.”
Their experience working with mannose
will be useful for other work. “Many microbial pathogens, including those
involved in malaria and tuberculosis, use mannose,” says Assoc Prof McConville. “In fact,
the human immune system recognises mannose compounds as a danger signal, a
warning of disease.”
It turns out, for instance, that
mannose is an important component of the cell wall of Mycobacterium
tuberculosis which causes TB, still the world’s biggest bacterial killer,
accounting for between two and three million deaths a year. A major problem in
coping with tuberculosis is the cell wall itself. “It stands alone from other
bacteria,” says Assoc Prof McConville, “a waxy, impervious barrier resistant to almost all
commonly used antibiotics.”
But Assoc Prof McConville’s team has recently
revealed a chink, and it involves mannose. It has long been known that the cell
walls of TB bacteria included mannose-containing compounds. Until recently, it
was thought these were important for bacterial invasion, but not necessarily for
cell wall assembly. But the Bio21 Institute researchers now have shown that without
mannose the bacterium cannot form new walls and divide, and it eventually dies
Researchers in the laboratories of
Assoc Prof McConville and Dr Williams are now examining how these molecules are made, and have
already begun to develop inhibitors that will disrupt the wall construction
process and thereby prevent the bacterium from spreading.
Images
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Leishmania (Photo courtesy of Malcolm McConville) |
Assoc. Prof. Malcolm McConville |
Leishmania Acido Drop (Photo courtesy of Malcolm
McConville) |
Merozoites Bursting Out (Tuberculosis) (Photo courtesy
of Malcolm McConville) |
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THE
BIO21 INSTITUTE: OPENING CEREMONY
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