. 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 group in Australia. These drugs also lead to increased bradykinin levels, a hormone that decreases blood pressure and protects against heart disease.
9. Three dimensional structure of human Chorionic Gonadotropin hCG - 1994
Dr Neil Isaacs, together with Professor Frank Morgan, a former Director of SVI, and their groups determined the three-dimensional structure of human chorionic gonadotropin in 1994. This hormone is made by the embryo soon after conception and later made by the placenta. The hormone plays an essential role in the early stages of pregnancy. Early pregnancy testing is often based on detecting hCG in urine or blood. Knowledge of the structure of hCG has helped in the understanding of the structure and function of a number of other hormones essential for reproduction that are related to hCG.
10. Role of PTHrP in foetal development – 1988
When Professor Jack Martin and his team discovered PTHrP it was thought that it was present in the circulation only in cancer, where its excess causes complications. The research team
then discovered that it also circulates in the blood of the foetus during pregnancy and promotes the transfer of calcium from mother to foetus to
provide calcium for the foetal skeleton.
11. Role of PTHrP in breast cancer - 1988
Professor Jack Martin and his research group were interested in discovering why patients with certain cancers so commonly
developed a high blood calcium level, causing nausea, vomiting,
dehydration and often ending in coma. They discovered parathyroid
hormone-related protein (PTHrP) in the 1980s and went on to purify, clone and synthesise it. They showed that PTHrP is the cause of high blood calcium levels in most patients and also that PTHrP produced by certain cancers, especially of the breast, helps those cancers to establish as secondary growths in bone.
12. The Sequenator – 1967 (Australia’s second most highly cited paper)
Proteins are the essential building blocks of the body and all diseases involve a change in protein behaviour. Knowledge of a protein’s