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New beamline promises faster drug development

The existing protein crystallography beamline at the Paul Scherrer Institute.

A SFr20 million deal, which could speed up the discovery of new drugs, has been announced at the Paul Scherrer Institute (PSI) in Villigen.

The PSI is building a second machine for scientists investigating the structure of proteins.

The device, known as a beamline, delivers high-intensity x-rays so that they can penetrate tiny protein crystals and reveal their composition.

Switzerland’s pharmaceutical giants, Novartis and Roche, have joined forces with the Max Planck Society in Germany to finance the new beamline.

Potential drug targets

“At the moment, there are about 500 different protein molecules used as targets for prescription drugs,” explained Nobel prize-winning chemist, Hartmut Michel, director of the Max-Planck Institute for Biophysics in Frankfurt, Germany.

“But the body has at least 30,000 genes, probably many more, and thanks to genomics, we will know much more about the role of these other proteins and many will appear as potential targets for drugs.”

It is a view shared by René Imhof, Head of Pharma Research at Roche.

“Based on the genome and proteomic analysis which we are carrying out, we would expect something in the range of 10-15,000 targets which might be available for drug design,” he told swissinfo.

Huge demand

The existing protein crystallography beamline has been in huge demand from industry and university researchers.

A year of experiments convinced Roche that the future lay in financing a second beamline.

“We had a number of problems which could not be solved at Roche’s in-house laboratories in Basel,” said Imhof.

“So we came here with about 15-20 crystals and we immediately succeeded with two of them. In one case, we solved the structure of a so-called human membrane protein.”

Until the Roche discovery, which is still unpublished, researchers had only managed to calculate the structure of a handful of human membrane proteins although it is estimated that there are at least 10,000 of them.

Since 80 per cent of all drugs act on membrane proteins, it is believed they offer huge potential for future drug development.

Rapid access

For many tasks, the Swiss Light Source at the PSI is one of the most advanced machines of its kind in the world.

“Protein crystallography is one of the key technologies to discover and develop innovative drugs and for this we need the best beamlines available,” said Hans Widmer, head of the protein structure unit of Novartis.

For Roche and Novartis, geographical proximity to their research centres in Basel also played an important role in the decision to fund the new apparatus.

“One of the most important factors is quick and flexible access because to grow crystals for these types of measurements is time-consuming and unpredictable,” said Widmer.

“Once you have succeeded, you want to be able to measure as quickly as possible and avoid any problems with the transport of the crystals.”

Financial incentive

The experts agree that the new project will boost Switzerland’s reputation for cutting-edge research. Financial stakes are also high.

For the medical profession, the most important class of molecules as targets for drugs are the so-called G-protein coupled receptors.

About 60 per cent of all drugs, prescribed by doctors, act on this class of molecule. For example patients with high blood pressure take compounds to block the action of this receptor while people with asthma will use a closely related compound, which activates the receptor to increase blood flow.

It is estimated that the pharmaceutical market for drugs acting on G-protein coupled receptors is worth $200 billion (SFr290 billion) annually.

There are about 500 of these receptors in the human body. Only about 30 are currently used as targets for drugs.

“More research is needed to find out what is the role of the receptors and their relation to disease,” said Michel.

“What we would really like to understand are the biochemical pathways of how a healthy human body works and what is wrong once a patient has a disease,” added Widmer.

“Proteins have important roles in healthy organisms but if we know what is going wrong when someone has cancer or an immune disease, then we have a better clue of how to intervene and how to produce drugs which fix the problem.”

Full house

The new beamline will cost about SFr6.7 million to set up and about SFr1.1 million to operate annually.

The Max Planck Society will meet half the costs with the other half shared between Roche and Novartis. They are planning to operate it for a ten-year period.

Three other beamlines, used for investigating new materials, are already operating at the Swiss Light Source (SLS).

By tinkering with the atomic structure of materials, scientists hope to create new properties, such as increased strength or heat resistance. One quest is the search for superconductors which operate at room temperatures.

At full capacity, the Swiss Light Source has enough space for 33 beamlines.

swissinfo, Vincent Landon

The Swiss Light Source probes the fundamental structure of matter with x-rays.
The machine makes electrons fly extremely fast and bends them with magnets.
As a result, they emit synchrotron light.
These synchrotron x-rays penetrate deep into a material and reveal its structure.
The SLS cost SFr159 million and began operating in 2001.

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SWI - a branch of Swiss Broadcasting Corporation SRG SSR