Studying disease proteins' interaction may lead to effective therapies

Washington, October 21 : A leading European scientist has revealed that his new research has provided significant insights into how proteins in human cells interact and "talk" to one another, and thereby led to a better understanding of how medications work.

Giulio Superti-Furga, a professor at the Centre for Molecular Medicine of the Austrian Academy of Sciences, hopes that such insights may result in more effective therapies.

"Most of the time the mechanism of action of drugs is ill understood and we often do not even know the primary target of the drugs we swallow daily. We do not know how these drugs work at the molecular level, and side effects can have serious consequences," he said.

For his research, Prof. Superti-Furga uses a 'proteomics' approach to understanding precisely how certain proteins that are key drug targets organise themselves in the cell, and how they make complex interactions with often dozens of other proteins.

"Proteomics is a way of joining the dots together to give us the bigger picture," he said.

His team has been investigating a particular enzyme, a tyrosine kinase called Bcr-Abl, which is involved in leukaemia.

The researchers has revealed that a drug is available that acts on the enzyme, but it eventually loses its efficiency as patients become resistant to it.

"We need to understand the relationship between the drug and the target. Can we understand the 3-d protein as a molecular machine much better?" he said.

Superti-Furga's lab in Vienna has used a range of proteomics techniques to isolate the enzyme, and dissect its constituent parts.

They have discovered that the protein exists as a complex of some 46 separate components, and operates as a giant molecular machine, with each part in close communication with the others.

"It is clear that tyrosine kinase inhibitors do not simply inhibit the enzyme, but rather remodel the machine. So drugs do not simply ablate things, they interfere with the equilibria of networks. If we can understand how these proteins interact, in the future people might say we should target this pathway or that network'; by targeting multiple nodes we will be able to maximise the good side effects against the bad side effects," the researcher said.

The team say that their main objective is to develop methods to understand how the human body can recognise invading foreign genetic material, from bacteria or viruses for example, and distinguish it from its own, innate genetic material.

They hope that their work will provide important insights into how the body defends itself against invading organisms.

Superti-Furga made a presentation of his team's work at the European Science Foundation's 3rd Functional Genomics Conference in Innsbruck, Austria, held on 1-4 October.

ANI