to cause Alzheimer’s disease. This work has lead to detailed insights into the function of the protein and is being used to develop novel drugs that will inhibit the breakdown of the protein that causes release of the toxic fragment with the potential to prevent Alzheimer’s disease. In collaboration with Professor Colin Masters, Mental Health Institute and Melbourne University.
4. Bacterial pore forming protein structures – 1998-current
Protein toxins are produced by a variety of living organisms, particularly bacteria, certain insects, poisonous reptiles and stinging marine invertebrates. As offensive weapons these toxins can aid digestion or degeneration of the host whilst as defensive weapons they can protect by killing invaders. Of the more than 300 protein toxins characterised to date, at least a third act by punching holes or pores in cell walls causing cells to die.
Professor Michael Parker and his lab have been world leaders in visualising the three-dimensional structures of pore-forming toxins from bacteria that cause devastating diseases including pneumonia, meningitis and gangrene. The structures have revealed the detailed mechanism behind how these toxins work and in doing so provided new insights into how other related toxins work such as diphtheria and anthrax toxins.
5. AMPK and obesity – 1994
AMPK is an enzyme that regulates energy metabolism in response to diet
and exercise and is thought to mediate their health benefits. In the
brain AMPK controls appetite whereas in other tissues it increases
energy production and reduces energy expenditure in response to demand.
Because of its central role in energy metabolism AMPK has become a
pharmaceutical drug target for the treatment of a number of age onset diseases that include obesity, type 2 diabetes, cardiovascular disease
and cancer. Professor Bruce Kemp and his group, in collaboration with Dr Lee Witters at
Dartmouth Medical College New Hampshire, the were first to identify AMPK in 1994 and this paved the way for a new era in metabolism research.
6. Osteoclast regulation and biology in arthritis, osteoporosis and bone cancer - 1988-current
Osteoclasts are the only cells that are able to break-down
bone in the continuing cycle of bone building and bone breakdown. Their production and activity needs to be very tightly regulated. Professor Jack Martin and his team have discovered a number of the locally produced factors in other bone cells that control osteoclasts, and this has led to much greater understanding of diseases such as osteoporosis, rheumatoid arthritis
and the spread of cancer to bone.
7. Twitchin kinase and autoregulation – (published in Nature in 1994 and 1996)
The human genome codes for over 500 protein kinases that are regulatory enzymes controlling all of the body’s functions. One
important subfamily of protein kinases is regulated by the
calcium-binding protein calmodulin and these enzymes are turned off in
the absence of calcium. These protein kinases have important functions in the control of blood vessel contraction and memory.
Professor Kemp showed that these enzymes are turned off because a part of their structure binds in the catalytic site and in collaboration with Dr Jörg Heierhorst, Professor Bostjan Kobe and Professor Michael Parker solved
the structure of twitchin kinase, a member of the calmodulin-regulated protein kinase subfamily that proved the mechanism of autoregulation. Their subsequent work showed this concept of regulation extends to other proteins such as enzymes and transport proteins.
8. Angiotensin and bradykinin: insights into the treatment and prevention of heart disease - 1994
The hormone angiotensin regulates blood pressure by controlling blood vessels, and by controlling the water and salt balance of the body. In Western societies with high salt content diets, even normal levels of angiotensin can cause high blood pressure, heart disease and stroke. The drugs most commonly used to treat these diseases either block angiotensin production or block its effects, and together form the most frequently prescribed drug 