Medical molecules
Unravelling the molecular mysteries of disease is giving a group of University of Auckland researchers a deeper understanding of the causes of
disease and helping them in the search for new therapeutic targets.
Professor Ted Baker and his colleagues, Drs. Peter Metcalf, Shaun Lott and
Vickery Arcus, from the School of Biological Sciences, are particularly interested in proteins because they are the molecules which carry out all the
essential processes in living things.
Developing their knowledge of the three-dimensional structures of proteins may open the way for controlling biological activities through structure-based drug design or protein engineering.
“Structural biology is an extremely fast growing, fast evolving area of research,” Professor Baker says. “The advances in genome sequencing have
further accelerated this. We now use structural biology to help discover the
functions of the many genes and proteins whose functions are a mystery
at present.”
Professor Ted Baker
Key words:
– tuberculosis, protein structures,
antibiotic resistance.
Key facts:
– tuberculosis kills 500 New
Zealanders every year
– the prevalence of tuberculosis is
rising, with rates among Maori 5
times those of Europeans, Pacific
peoples 12 times and other ethnic
groups 35 times greater than
European rates
– antibiotic resistance is rising
rapidly
– new anti-bacterial drugs are
urgently needed.
Aims of this research:
– understanding molecular
mechanisms of disease
– definition of new drug targets
– structure-based design of new
drugs.
What this research has shown:
– new protein structures as drug
targets
– previously unknown disease
mechanisms
– new technologies developed.
He says that there are basically two strands to this research: “One is to
understand disease at the molecular level by looking at the structure and
function of key proteins, and the second is to use the proteins themselves
as the target for new drugs.”
The team uses X-ray crystallography to work out a protein’s precise
three-dimensional structure, then collaborates with other biomedical researchers to further this work. For example, their work (with a Massey University team) on the kiwifruit enzyme, actinidin, was used in the design of
anti-malarial drugs by San Francisco researchers.
Professor Baker’s group is also part of an international group of more than
40 labs world-wide known as the International TB Structural Genomics
Consortium. Researchers in this consortium work together in a co-ordinated way, using the bacterial genome to identify potential new drug targets
against TB, and then analysing their three-dimensional structures.
“Our lab has recently solved the precise atomic structures of several enzymes essential for the viability of the bacterium. We believe that these are
good drug targets because they are essential for the bacterium but they are
not present in humans.”
Professor Baker’s team has also been working with the laboratory of Professor John Fraser, at the School of Medical Sciences, to determine the structures of superantigens and other toxins from the common human pathogens Staphylococcus aureus and Streptococcus pyogenes.
They are also investigating proteins that cause antibiotic resistance, and
understanding proteins that act on folic acid and may be useful in designing more effective anti-cancer drugs.
This research is funded by the Health Research Council of New Zealand, the Foundation for Research, Science and Technology, The University of Auckland and the
Centre of Molecular Biotechnology.
HRC01 2004
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Wellesley Street, Auckland, NZ
Telephone 64 9 303 5200 Facsimile 64 9 377 9988
Website www.hrc.govt.nz
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa